Final
NO, 5221,07
OF
IN
Berfconed for:
Triangle Institute
P.O. Box 12194
Triangle Bark
North Carolina 27709
Revised Final
25,
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30272-101
REPORT DOCUMENTATION
PAGE
1. REPORT NO.
EPA/530-SW-88-026
3. R*clplent'» Acctltion No.
PB88-195284
4. Title and Subtitle . .
. Subchronic Toxicity of Meta-Cresol in Sprague Dawley Rats
S. Report Dm
March 25, 1988
7. AuthOrU)
Dr. Dennis Dietz and Dr. L. Thomas Mulligan
S. Performing Organization Rtpt. No.
9. Performing Organisation Name and Addre»
Microbiological Associates,line.
5221 River Road
Bethesda, MC 20816
10. Project/Talk/Wor* Unit No.
11. Conlr.cltC) or Gr»nt(G) No.
Inilruclioni on Rfverit
(Formerly NTlS-3bt
Department of Commtrce
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Final Report
Study No. 5221,0?
SUBCHRONIC TOXICITY OF META-CRESOL
IN SERAGUE DAWUEY RATS
MBA Chemical No.: 24
Sponsor:
Sponsor Representative:
Research Triangle Institute
P.O. Box 12194
Research Triangle
North Carolina 27709
Dennis Dietz
Testing Facility:
Microbiological Associates Inc. (MBA)
5221 River Road
Bethesda, MD 20816
Initiation Date:
Completion Date:
October 03, 1985
January 04, 1986
L. Thomas Mulligan, Fh.li.
Study Director
Date
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Final Report
Study No, 5221=07
TABLE OF CONTENTS
Page
I. - SUMMARY 1
II. INTRODUCTION. 1
III. MATERIALS AND METHODS.. 1
A. Test Article. , i
B, Animals i
C. Experimental Design. 2
D. Statistical Analyses. 6
IV. RESUUTS.. ...... 6
A. Aralyses and Stability of Dosage Form Preparations 6
B. Mortality/Clinical Observations , 7
C, Body Weight.. , 8
D. Food Gonsuraption............ 8
E. Clinical Pathology. . .. 9
F. Ophthalmology ,. 9
G. Organ Weights, 9
H. Pathology. 9
V. DISCUSSION • 10
VI. PERSONNEL . . ........ 10
VII. ARCHIVES ...:... 11
VIII. PROTOCOL. 39
APPENDICES
APPENDIX A - TVD-WEEK I^NGE-FINDING/EXPIDRATORY STUDY
OF MEIA-CRESOL IN SERAGUE DAWLEY RATS...... A-l
APPENDIX B - ANALYTICAL CHEMISTRY METHODOLOGY B-l
APPENDIX C - CLINICAL PATHOLOGY METHODOLOGY C-l
APPENDIX D - INDIVIDUAL ANIMAL DATA D-l
APPENDIX E - OPHTHAIMDLOGY REPORT 1-1
APPENDIX F - PATHOLOGY REPORT. F-l
o,
O
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I. SUMMER?!
Final Report
Study No. 5221.07
study examined the toxic effects of meta-cresol in Sprague Dawley
rats following 13 weeks of oral gavage administration. Dose levels
studied were 0, 50, 150 and 450 mg/kg/day. The biological effects of
m-cresol, central nervous system depression and reductions in body
weight gain, were generally restricted to the high dose level under
the conditions of the present study. Although a slight reduction in
weight gain also occurred for mid-dose males but not females, no other
manifestations of m-cresol toxicity were seen for these animals or for
those at the low dose level. Thus, 50 mg/kg/day for meta-cresol
administered to male and female Sprague Dawley rats for 13 weeks
appears to represent the maximum dose tested in thisv study that
produced no evident adverse effects. . ;/
II. INTRODUCnON;
This report presents a preliminary evaluation of test data collected
to assess in rats the toxicity of meta-cresol when administered for 13
weeks by oral gavage. All methods and procedures were conducted in
accordance with the appropriate Microbiological Associates Inc. and
Pathology Associates, Inc. Quality Assurance Programs designed to
conform with FDA and EPA Good Laboratory Practices.
III. MATERIALS AND METHODS;
A. Test Article
m-Cresol, 4 kg, was received on 07/29/85 and was assigned MBA
chemical number 24. The source was Eastman Kodak Company,
Rochester, NY, 14650 (Lot No.- KL4A). The test article was
described as a yellow liquid and was 98.6% pure (according to
information provided by the supplier). The test article was
stored in its original container, a translucent plastic bottle, at
room temperature and ambient humidity. A total of 1836.8 g of the
test article was used for dosage preparation; an additional 20 g
were sent to ENSEOO, Inc. for chemical analysis.
B. Animals
One-hundred and thirty-seven male and one-hundred and thirty-five
female Sprague Dawley rats were obtained from Charles River
Breeding laboratores, Inc., Kingston, NY on September 18, 1985.
The animals were five weeks old upon arrival at MBA's animal
facility. The animals were in quarantine/pretest for approxi-
mately two weeks prior to initiation of treatment. The animals
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ATTENTION
PORTIONS OP THIS REPORT ARE NOT
FULLY LEGIBLE. DDE TO THE IMPORTANCE
OP THE MATERIAL IT IS MADE AVAILABLE
TO THE PUBLIC. HOWEVER, IT IS TEE BEST
REPRODUCTION" AYAIIABLS FROM THE COPT SERI
TO NTIS.
DOCUMENT COMPLETE AS PAGINATED PER SOURCE.
DIRECT QUESTIONS RESUMING- FROM
TO:
U.S. EPA
OSWER - HSCD
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Final Eeport
Study No. 5221.07
were housed two or three per cage during quarantine/pretest and
housed irxiividually following randomization to groups. The
animals were housed on Beta-Chip hardwood bedding in polycarbonate
cages which aecomodated animals to the upper weight range recom-
mended in the Guide,for, the Care and Use of Laboratory Animals,
CHEW, (NIH) No. 78.23. Ml test animals received Purina Labora-
tory Chow No. 5001 in block form and water (Washington Suburban
Sanitary Commission, Potomac Plant) ad libitum except during an
approximate 16-18 hour fast prior to necropsy.
Curing the study period, animals were housed in a teiperature-
controlled room with a 12-hour light/dark illumination cycle.
Animal room temperature was monitored continuously during the
study. In addition, animal room temperature and relative humidity
readings were checked and recorded once daily by animal care
personnel. Temperature and humidity readings were noted to be
above or below the protocol-specified ranges on several occasions
during the study. Monthly environmental data are summarized
below;
Egnth/Year
10/85
11/85
12/85
1/86
10/85
11/85
12/85
1/86
a
b
Number of
Readings
26b
31
3
26^
30
31
3
Protocol-required
Ttemrtfar-at-u-re* /him i d i
TEH
Mean
± S.D.
PES
iAIURE
Number (%) of leadings
Within the Protocol-
Range Reouired Range
a
! (deorees F)
71.6 ± 4.4 61-78
72.2 ± 1.1 70-74
-70.6 ± "6.4 48-78
78.3 ± 1.5 77-80
c
RELATIVE HUMIDITY (%)
47
37
15
14
range =
t"v "was i
.3
.8
.1
.3
69
nn1"
± 14.
± 11.
± 9.
± 4.
-75°
. reco
0 20-72
7 19-65
8 2-40
9 11-20
F
irdpd on thTpe* da
13 (50)
30 (100)
14 (45)
0 (0)
18 (69)
18 (60)
2 (6)
0 (0)
vs diip -hn t^chni —
cian oversight.
Protocol-required range = 35-65%
C. Experimental .Design
During the second week of quarantine, the animals were examined by
the Staff Veterinarian and were found to be acceptable for use on
study. The. animals were randomized on the basis of body weight
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Final Report
Study NO. 5221.07
into four groups of 30 animals per sex. An animal was considered
eligible for randomization if its body weight was within ±20% of
the average weight for all animals of the same sex. Ten male and
ten female rats were also chosen for baseline hematology and
clinical pathology determinations. Baseline clinical pathology
animals were selected from animals not previously assigned to test
groups, vising a table of random numbers.
The following dose levels were selected by the Sponsor and were
administered once daily by oral gavage for 13 consecutive weeks.
Treatment Dose Level Number of Animals Dosage Fonnula-
Group (TO/ta/dav) Male Female tion (rag/ml)
1 0 30 30 0
2 50 30 30 10
3 150 30 30 30
4 450 30 30 90
5 Baseline Clin. Path. 10 10 •
The test chemical was diluted in corn oil to achieve the following
concentrations which allowed for a dosing volume of 5 nl/kg.
Dosage formulations were prepared fresh weekly throughout the
study, and were stored protected from light at room temperature.
American Biogenics Corporation, Decatur, IL tested the stability
of in-cresol dosage formulations following a 14-day holding period.
Additionally, the concentration of m-cresol in corn oil was
analyzed from dosage formulations used during Test Weeks 1, 2, 4,
8, and 13 by ENSICO Inc., Cambridge, M2L
All rats in the study received a unique test animal number which
appeared as an ear tag. A cage card appeared on the front of each
cage and contained the following information: study number,
animal number, test article name, treatment group name or number,
room number, dose level, strain, sex, receipt date, and start
date. The cage cards were color-coded as a function of treatment
group and sex.
The test article or vehicle (corn oil) was orally administered
once daily for 13 consecutive weeks commencing on 03 October 1985.
Animals were dosed up to the day prior to routine necropsy in
either Test Week 7 (interim sacrifice) or 14 (terminal sacrifice).
The gavage procedure was accomplished by the use of a rigid oral
feeding needle.
Non-fasted body weights were recorded on Test Day 1 and weekly
thereafter. Individual food consumption data were collected on a
weekly basis. Mbrbundity/mortality checks were performed twice
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Final Report
Study No. 5221.07
daily, once in the morning and once in the afternoon, and moribund
animals were killed and necropsied. The test animals were given
couplets physical examinations on a weekly basis.
Ophthalmology examinations were performed during the quarantine
period and in Test Week 13 by Dr. Nancy Bromberg, Diplomate,
American College of Veterinary Ophthalmologists. This procedure
was done by indirect ophthatlmoscopy, and only animals which were
free of visable lesions, or had congenital or incidental lesions
which were not considered to interfere with the study, were
considered for test animal selection.
Blood samples were collected from ten rats per sex designated for
baseline clinical pathology determinations, ten rats per sex per
dose sacrificed during Test Week 7, and ten rats per sex per dose
sacrificed at study termination (Test Week 14). Blood was
obtained via orbital sinus puncture while under 002 anesthesia.
Animals were fasted for approximately 16-18 hours prior to blood
collection. The following hematology and clinical chemistry tests
were performed:
HematologY
Hencglobin
Hematocrit
Eythrocyte count
Total and differential leukocyte count
Prothrcmbin time (FT)
.Activated partial ttirombopiastin tine (APTT)
•'.Reticulocyte count
Clinical Chemistry
Sodium
Chloride ,
Potassium
Calcium (not measured at baseline or at the interim sacrifice due
to technician error)
C02
SGFT
SCOT
Glucose
BUN
Direct and total bilirubin
Alkaline Fhosphatase
Total Cholesterol
Albumin
Globulin (calculated)
Total protein
A/G ratio (calculated)
yrn,
e
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Final Report
Study No. 5221.07
Clinical chemistry (cont.l
Creatinine
Phosphorus
Urine specimens were obtained from ten rats per sex per dose which
were sacrificed during Test Week 7 and from ten rats per sex per
dose which were sacrificed during Test Week 14. The urine
specimens were collected from metabolism pans into gauze-filtered
urinalysis cups during the overnight fasting period. The
following urinalysis parameters were assessed:
Urinalysis
Appearance
Volume
Color
Specific gravity
pH
Protein
Glucose
Ketones
Bilaxubin
Urdbilinogen
Hemoglobin
Microscopic examination
Clinical pathology methodology is included in Appendix C.
Complete gross necropsy examinations were performed on rats found
dead during the study and those killed at the interim and terminal
sacrifice intervals. Eats assigned to the interim sacrifice
(identified at study onset) were killed in random order over a
consecutive two-day period (November 18-19, 1985). At the
terminal sacrifice, all surviving rats were killed in random order
over a consecutive three-day period (January 2-4, 1986). All rats
were anesthetized with CQ2 and exsanguinated by bleeding from the
posterior vena cava. Animals were fasted overnight prior to
necropsy.
She necropsy procedure included a thorough and systematic
examination and dissection of the animal viscera and carcass, and
collection and fixation of the following tissues/organs in 10%
neutral buffered formalin;
All gross lesions Ovaries
Brain (3 levels) Corpus and cervix uteri
Spleen lye
Bone (with marrow) Pituitary
Skeletal muscle lOTph node (mandibular)
s
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Final Report
Study No. 5221.07
Salivary gland Spinal cord
Heart Mammary gland
Thynus Aorta
Thyroid (with parathyroid) Sciatic nerve
Lungs (with mainstem bronchi) Pancreas
Trachea Esophagus
Liver Kidneys
Stomach Urinary bladder
Small and large intestine Testes
Adrenals Prostate
All of the above tissues of all control and high dose animals
sacrificed at study termination were submitted for histopathologic
examination. Gross lesions from the rats killed at the interim
sacrifice were also submitted for microscopic evaluation.
During the terminal sacrifice, in addition to terminal body
weight, the heart, liver, spleen, brain, kidneys (individually),
gonads (individually), adrenals, and ttyroid/parathyroid were
weighed.
D. Statistical Analyses:
Body weight, food consunption, clinical Chemistry, hematology, and
organ weight data were analyzed (by sex) by one-way Analysis of
Variance tests with Dunnett's t-test employed if a significant F
ratio was found (p < 0.05). Individual ;inimal data is included in
Appendix D.
IV. RESULTS
A. Analyses and Stability of Dosage Form Preparations
m-Cresol in corn oil was found to be stable for at least 14 days
at the concentrations tested. Additionally, the analyses of the
dosage form preparations used during Test Weeks 1, 2, 4, 8, and 13
indicated that target concentrations were generally within an
acceptable range. Ten of the 15 preparations were within ±10% of
the intended concentration. Of the remaining five, three were for
the 10 mg/ml level (low dose). These samples were 13-16% less
than target. The remaining two samples were 12-14% over target,
one each for the 30 and 90 mg/ml intended concentrations (Tables
la and Ib). Purity analyses performed by ENSECO, Inc. indicated
that the bulk test chemical was 99.5% pure..
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Final Report
Study No. 5221.07
B. Mortality/Clinical Observations
One high, dose male (#3504) was found dead on Test Day 5. Gross
necropsy and tissue morphologic examinations failed to determine
the cause of death, although gavage error or aspiration of the
compound were considered possible explanations (Section IV.H -
Pathology). No clinical signs were observed for this animal prior
to death. No other animals died during the treatment period.
Lethargy/ tremors, hunched posture, and rough hair coats were the
most frequently noted post-dosing observations, and were seen only
in the high dose group animals. All high dose males and/or
females exhibited lethargy after dosing on days 3, 7, 8, 11, 12,
13, 14, and 20. Tremors were observed after dosing in 4/30 high
dose males on day 3, and 2/29 high dose males on day 11. Post-
dosing tremors were observed in the high dose females with the
following incidences: 1/30, day 7; 8/30, day 8; 4/30, day 11?
30/30, day 13. All high dose females appeared hunched and unkempt
on day 14 of the study.
Treatment-related clinical signs of toxicity were also observed on
occasion in the high dose rats at the weekly physical examination
intervals. The incidences of relevant clinical signs are
summarized below:
Incidence of significant Clinical Signs in High Dose Batsa
Weeksb
1
2
8
11
12
13
Letharqy_
M
5/29
8/19
9/19
F
9/30
9/30
7/20
7/20
Tremors
M
4/19
4/19
F
2/30
2/30
5/20
2/20
Hunched
M F
30/30
Dvspnea
M F
2/20
1/20
Number of animals exhibiting sign/number alive at the end of
the indicated week.
Only those weeks during which relevant signs were observed
are presented.
No clinical signs of toxicity were observed in rats treated with
the mid or low dose of m-cresol.
1
1
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Final Report
Study No. 5221.07
C. Body Weight
Dose-dependent reductions in'body weight were observed for males
receiving 150 and 450 mg/kg/day of m-cresol. significantly lower
. body weights were seen at weeks 6 through 12 and week 14 for the
150 mg/Kg/day dose group males, and at weeks 2 through 14 for the
high dose males. For females, body weights were similar to
controls throughout the study for all treated animals except for
week 11 when the high dose females had a significantly lower body
weight.
Dose-dependent reductions in body weight gain were seen for males
administered 150 mg/kg/day or greater. Approximate 20-25% and
10-15% decreases were seen at the 450 and 150 mg/kg/day levels,
respectively. Statistically significant (p < 0.05) reductions in
weight gain were noted for the high dose males during weeks 1
through 13 and for the mid dose males during weeks 4 through 13.
The mid dose males showed an average weight loss of approximately
12' grams between weeks 13 and 14. Weight loss of this magnitude
was not seen in any other test group at this time. A slight
reduction in food intake (approximately 6 g/day) was also noted
for the mid dose males during the last week of the study.
For females, an approximate 10-15% decrease in body weight gain
was seen for the high dose animals throughout the study. These
redactions, however, were only statistically significant
(p < 0.05} during the first week of the study. Body weights for
mid dose females and low dose males and females did not appear to
be affected by m~cresol treatment (Tables 2-5)..
D. Food Consumption
Slight decreases in food intake, approximately 10-15% were
generally seen throughout the study for males at the high dose
level. Significantly (p < 0.05) lower than control mean food
consumption values were noted for the high dose males during weeks
1 through 4, 6 through 9 and 11. For the high dose females, a
significant reduction in food intake was observed at week 1, and
significant increases were observed at weeks 4 and 6.
Scattered significant increases and decreases in food consumption
were also noted for the mid and low dose animals. Mid dose males
showed signficant decreases in food consumption for weeks 3, 6, 8,
12, and 13, while mid dose females showed signficant increases for
weeks 4 and 11, as compared to the respective controls. Signifi-
cantly lower food consumption values were noted for the low dose
males during weeks 1, 2, 9, 11, and 12. Food consumption values
for females at the low dose level were similar to controls
11
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Final Report
Study No. 5221.07
throughout the study except for week 4 when a significantly higher
food consumption value was noted.
E. Clinical Pathology
Clinical chemistry, hematology, and urinalyses parameters did not
appear to be affected by m-cresol treatment. Sporadic increases
and decreases were observed which were not considered biologically
significant (Tables 8-15, and Appendix D).
F. Ophthalmology
The Ophthalmology Report is contained in Appendix E. Treatment-
related ophthalmic lesions were not seen for rats receiving
m-cresol.
G. Organ Weights
Organ weights did not appear to be affected by m-cresol treatment.
Sporadic increases and decreases were seen which were not
considered biologically significant. The slight increases seen
for relative brain weights of males at the mid and high dose
levels reflect reductions in body weight gain for these animals.
Absolute brain weights were unaffected. Similarly, absolute but
not relative liver weights were decreased for these animals
(Tables 16-19).
H. Pathology
The Pathology Report is shown in Appendix F. Treatment-related
gross and Mstornorphologic lesions were not in evidence.
Although not treatment-related, there was a high prevalence of
incidental lesions in both the high dose and osntrol group
animals, including lymphoid hyperplasia and perivascular
lymphocytic infiltration. A possible explanation for these
inflammatory lung changes may be that the cresol vapors caused
irritation, in that the control group animals may have been
exposed by proximity to the dosed rat cages. No indications of an
infection by an adventitious microbial agent was evident.
Animal #3504, a high dose male, was the only animal found dead
during the course of the study. At necropsy, the lungs were red,
and blood was present in the thoracic cavity. lung congestion was
present microscopically, but no cause of death was determined,
although gavage error or aspiration of the compound were
considered possible explanations.
1
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Final Report
Study No, 5221.07
V. DISCUSSION
This study evaluated the oral toxicity of meta-cresol in Sprague
Dawley rats when administered for 13 weeks by gavage. One high dose
male was found dead on Test Day 5. The cause of_ death was not
evident, although it may have been associated with gavage error or
complications. Sane of the remainijig high dose males and females
occasionally exhibited lethargy and tremors.
In addition, high dose males showed significant (p < 0.05) reductions
in body weight gain during all weeks of the study. For high dose
females, body weight gain was numerically lower than the control
throughout the study, but was significantly lower only at week 1.
Males at the mid dose level also showed reductions in body weight
gain, which were statistically significant during weeks 4 through 13;
however, clinical signs of toxicity were not evident for these
animals.
Clinical chemistry, hematology, and organ weight measurements failed
to detect treatment-related changes. In addition, ophthalmology and
pathology examinations did not identify m-cresol target organs.
In summary, the biological effects of m-cresol, central nervous system
depression and reductions in body weight gain, were generally
restricted to the high-dose level under the conditions of the present
study. Although a reduction in body weight gain also occurred for mid
dose males but not females, no other manifestations of m-cresol
toxicity were seen for these animals or for those at the low dose
level.
VI. PERSONNEL:
L. Tom Mulligan, Ri.D. served as Study Director, and was responsible
for the overall conduct of the study. Barry S. 'Levine, D.Sc.,
Diplomate, American Board of Toxicology, was Study Toxicologist and
was responsible for the in-life portion of the study. Dr. levine was
also reponsible for clinical pathology data. Lucas H. Brennecke, DVM,
Diplomate, American College of Veterinary Pathologists, was
responsible for gross necropsies and histopathologic evaluations.
John Miller, DVM, was responsible for laboratory animal care. Harry
J. Paulin, M.S. served as Study Chemist, and provided dosage
formulations and analytical chemistry services. Nona S. Karten, M.A.r
was responsible for the Quality Assurance Program. Mike Schulz, B.A.,
and Brian Makle, B.S., were responsible for the collection of in-life
test animal data.
10
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VII.
Final Report
Study No. 5221.07
The raw data and final report are archived at Microbiological
Associates Inc., 5221 River Road, Bethesda, MD 20816 with the
following exceptions. Pathology specimens including wet tissues,
blocks and slides, and original necropsy forms are temporarily
archived at Pathology Associates Inc., 10075 Tyler Place, Hyatt
Park II, Ijarosville, MD 21754 and will be transferred to the MBA
Archives upon Sponsor approval of the final report.
VIII. PROTOCOL;
The study protocol and all protocol amendments for the subchronic
toxicity of m-cresol in Sprague Dawley rats are presented following
the report tables.
11
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Study 5221.07
TABLE la
SUBCHRONIC TQXICTTY OF MBIArCRESOL IN SERAQJE DaWLEY RATS
CQNCENTFJO'ION OF MEJ1A-CRESOL IN CORN OIL (rag/ml)
STABILITY ANALYSESa
Sample
_ Number
CQ221A85
C0223A85
Date Target Concentration frocr/rolV
Mixed Cone, fmcf/ml) Zero Day 14-Day
9/28/85
9/28/85
10
90
10.58
104.6
10.98b
100.7
Percent
Difference*
+3.8
-3.7
*Pereent Difference = 14-Day Value minus.Zero Pay, Value x 100
Zero Day Value
aAnalyses performed in duplicate by American Biogenics Corporation unless
noted otherwise.
^Analyses performed in triplicate.
11-a
5
MICROBIOLOGICAL
ASSOCIATES INC.
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Study 5221.07
TABLE Ifo
SUBCHRONIC TOXICrTY OP META-CRESOL IN SERAGUE DAWLEY RATS
CONCENTRATION OF META-CRESOL IN CORN OIL (ng/ml)
FORMULATION ANALYSES3
Target
Concentration
(vt3/ml) 1
0 ND
10 8.4
30 31,7
90 96.5
2
ND
9.3
34.2
100.8
Test Week
4
ND
9.5
30.1
94.8
8 13
ND ND
8.5 8.7
27.9 27.4
87.3 93.9
K °
&
"Analyses performed by ENSECO Inc. (formerly ERGO), Cambridge, MA unless otherwise noted.
ND = Not detected above the minimum reporting limit of 1.0 mg/ml.
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Study No. 5221.07
TABLE 2
SUBCHROHIC TOX1C1TY Of META-CRESOl IN SPRAGUE DAWLEY RATS
HALE SOOT WEIGHT DATA (g)
TEST
WEEK 0 rug/ kg/day
1 * 220 i
2 283 ±
3 333 ±
4 376 t
5 412 1
6 440 s
7 468 ±
8 497 *
9 514 *
10 534 ±
11 548 ±
12 566 i
13 576 i
14 580 ±
a
Weights taken on
12( 30)
17C 30}
24( 30)
29C 30)
32C 30)
35 C 30}
38( 30)
47C 20)
50< 20)
50C 20)
54( 20)
58< 20)
57{ 20)
57{ 20)
Test Day
" •- Statistically significant
using AH OVA and Dunnett's
Results presented
as mean
50 mgAg/day 150 mg/kg/day
217 t
282 ±
331 ±
370 i
404 i
433 i
460 t
434 ±
504 t
524 t
549 ±
562 ±
568 t
578 i
1 prior to
14( 30) 220 t 10< 30}
18C 30) 282 i 15< 30)
221 30) 326 ± 19C 30)
27( 30) 366 i 23C 30)
27{ 30} 392 t 28C 30)
31 ( 30) 413 ± 27C 30}*
33< 30) 439 t 30C 30)*
34{ 20} 451 * 42( 20)*
36( 20} 470 J SOC 20}*
34{ 20) 49S ± 47( 20)*
35( 20) 51T i 42( 20)*
35( 20} 529 ± 44{ 20}*
37( 20) 542 ± 39( 20}
36( 20) 529 i 47( 20}*
dosing.
450 rag/kg/day
215 t 14( 30)
269 ± 22 C 293*
311 t 26C 29)*
350 ± 31 ( 29)*
362 i 43C 29!"
398 t 39C 29)*
423 4 39C 29)*
427 i 45( 19)»
436 i 48( 19)*
458 t 48( 193*
475 ± 44( 19)*
493 ± 46< 19)*
497 ± 45( 19)*
502 ± 51( 19)*
difference from control group
T-Test (P<=0.05).
± standard'
deviation ( N )
17
13
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Study Ho. 5221.07
TABLE 3
SU3CHRONIC TOXICITY OF META-CRESQL IN SPRACUE DAWLiY RATS
KALE BODY WEIGHT GAIN DATA Cg>
TEST
WEEK
1
2
3
4
5
6
7
8
9
10
11
12
13
0 mg/kg/day
63 t
113 i
156 ±
192 t
220 ±
248 i
276 S
293 ±
313 i
327 i
346 ±
355 ±
359 t
8(
!«
21 C
24<
27C
30(
40C
43(
43(
47(
51C
50(
52(
30)
30)
30)
30}
30}
30)
20)
20}
20)
20)
20)
20)
20)
50 mg/fcg/day
65 t
114 i
153 t
187 t
216 ±
242 ±
268 t
2Sa ±
308 ±
332 ±
345 ±
351 1
361 t
7(
1K
16(
17C
21C
24{
25 (
28(
26(
28<
28 C
29<
30(
30}
30)
30)
30}
305
30)
20)
20)
20)
20)
20)
20)
20)
150 mg/kg/day
62 i
106 *
146 i
172 t
193 i
219 *
229 i
249 i
274 i
291 ±
307 ±
320 1
308 i
9(
13<
17C
23{
22(
25 <
39(
49(
45 (
38{
39<
34{
42C
30)
30)
30)
30}*
305*
30)*
203*
20}*
20)*
203*
20)*
20}"
205*
450 mg/kg/day
54 ±
96 i
135 t
148 *
183 ±
209 *
213 t
222 *
245 s
262 ±
:.-79 *
284 t
288 i
J2( 29}*
14( 29)*
22( 29)*
33( 29}*
E8( 29)*
28( 29)*
35C 19)*
39C 19)*
38( 19}*
32( 193*
35{ 19)*
33( 193*
39( 193*
Statistically significant difference frwn control group
using AMOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean ± standard deviation ( N }
14 -IS
-------
Studv Ho. 5221.07
TABLE 4
SUBCHRONtC TQXICSTf OF META-CRESOL IN SPRAGUE DAUIEY RATS
FEMALE BOO? WEIGHT DATA
-------
Study No. 5221.07
TABLE 5
SUBCHRON1C TOX1CITY OF META-CRESOL IH SPRAGUi DAULET RATS
FEMALE BOOT WEIGHT GAIN DATA (g)
TEST
VEEK
1
2
3
4
5
6
7
8
9
10
. 11
12
13
0 mg/ kg/day
29 i
50 ±
69 ±
84 t
93 t
105 ±
112 ±
117 t
124 *
134 ±
135 i
137 *
144 t
5< 30)
7{ 30}
10( 30)
11< 30)
11C 305
12< 30)
12( 20)
15C 20}
1S< 20)
17( 20)
13C 20)
18( 20}
20( 20)
50 mg/kg/day
29 *
48 i
64 ±
79 1
90 ±
99 t
106 *
110 i
115 t
126 t
129 t
132 i
135 i
8t 30)
10{ 30)
IK 30)
12C 30)
13C 30)
14( 30)
17C 20)
18( 20)
19( 20)
2t< 20)
19( 20)
20( 20)
20( 20)
150 mg/fcg/Clay
27'*
43 t
67 t
81 £
90 ±
100 t
105 *
112 ±
117 i
124 t
133 t
130 *
133 s
6C 30)
7C 30)
9{ 30}
1U 30)
12< 30)
13( 30)
17( 20)
17( 20}
21C 20)
21 C 20)
24( 20)
22C 20)
30( 20)
450 mg/kg/dsy
25 ±
47 t
64 t
76 ±
33 i
99 S
99 ±
103 t
107 i
115 t
121 t
123 *
127 i
a< 30)*
15( 30)
12( 30)
14< 30)
17C 30}
19( 30)
22C 20)
24( 20)
30{ 20)
27C 20)
28C 205
30{ 20)
33( 20}
Statistically significant difference from control group
using ANQVA and Dunnett's T-Test CP
-------
Study Na. 5221.07
TABLE 6
SUBCHRONIC TOXIC1TY OF META-CRESOl IH SPRAGUE DAUIEY RATS
HALE FOOD CONSUMPTION DATA Cg/day)
TEST
UEEK 0 mg/kg/day 50 mg/kg/day 150 mg/kg/day 450 mg/kg/day
1 27.4 s 2.5( 30) 23.5 ± 8.9C 29)* 26.3 ± 2.7( 30) 23.3 ± 2.6C 293"
2 23.5 t 2.91 30) 25.7 ± 2.5C 30)* 27.4 ± 3.2( 30) 25.6 * 3.2C 29)*
3 27.8 ± 2.2C 30) 26.8 ± 3.4( 30) 24.4 4 4.3C 30>* 23.9 ± 3.SC 29)*
4 28.3 t 3.3( 30) 26.5 * 4.6< 30) 25.6 ± 7.DC 30) 22.5 ± 5.8C 29)*
5 26.8 * 3.4< 303 24.7 t 7.0C 30) 30.1 * 6.9{ 30) 25.5 s 3.4( 29)
6 26.2 ± 3.2C 30) 24.3 ± 3,5( 30) 19.5 ± 4.4< 30}* 23.1 * 4.9C 29)*
7 24.9 ± 2.91 30) 24.3 * 2.6( 29) 22.6 t 3.8C 30) 21.0 i 5.5C 29)*
8 26.0 ± 3.It 20) 24.5 * 2.8( 20) 22.3 t 6.1C 20)* 21,7 i 5.5C 19)*
9 26.5 ± 3.0( 20) 24.3 ± 2.4{ 20)* 24.6 i 2.5C 20) 24.1 t 3.4( 19)*
10 25.6 t 2.9< 20) 24.5 ± 2.0( 20) 25.0 ± 2.7( 20) 24.7 ± 2.9( 19)
11 26.7 ± -3.0( 20) 23.3 t 2.6( 20)* 24.5 i 2.3( 20) 24.0 t 3.9( 19)*
12 26.5 ± 2.4( 20) 23.1 t 3.5( 20>* 24.4 i 1.8( 20)* 24.4 ± 2.7C 19)
13 22.2 t 2.1( 20) 20.4 ± 3.0( 20) 13.5 1 3.4< 20)* 20.9 t 3.7C 19)
* •- Statistically significant difference from control group
using ANOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean i standard deviation CM)
O -J
»i ±
17
-------
Study No. 5221.07
TABLE 7
SUSCMRONIC TOXICITT OF HETA-CRESQL IN SPRAGUE DAWLEt RATS
FEMALE FQOO CONSUMPTION DATA
4 16.8 i 3.4(30) 19.7 t 3.4(29)* 19.9* 1.8(303* 19.5 i 4.3(30)*
5 16.5 t 2.21 33) 17.3 i 2.4( 30) 15.3 ± 1.8( 30) 17.8 t 4.9( 30)
& 17.0 ± 1.8( 30) 16.3 * 2.3( 30) 17.1 t 2.0C 30) 21.6 * 3.5( 30)*
7 16.2 ± 4.8C 30) 18.1 ± 9.3C 30) 16.9 i 2.6( 30) 14.3 t 2.0( 30)
8 17.4 i 2.2E 20) 17.3 i 4.5( 20) 17.2 t 1.9{ 20) 16.2 i 2.1( 20)
9 16.7 t 2,0( 20) 16.9 * 2.1( 20) 16.4 i 2,1( 20) 15.9 * 2.3C 20)
10 16.1 i 1.6( 20) 17.3 t 4.9( 20) 15.8 ± 3.8C 20) 16.3 i 2.2( 20)
11 15.6 t 1.2( 20) 16.2 i 2.3C 20) 18.2 * 2.3( 20)* 16.1 t 2.2( 20)
12 16.7 ± 1.6( 20) 17.1 ± 1.9( 20) 18.0 t 2.4C 20) 16.9 i 2.0( 203
13 14.2 ± 1.7( 20) 13.6 ± 1.9( 20) 'H.3 ± 2.0( 20) 13.4 ± 2.1( 20)
* -- Statistically significant difference from control group
using AHQVA and Dunnett's T-Test (P<=0.05).
Results presented as mean ± standard deviation ( N )
18 -99
-------
Study No. 5221.07
TABLE 8
SUBCHROIUC TQXICITY OF META-CRESCL IN SPRAGUE DAULEY RATS
KALE HEMATQLQGY VALUES
[Interim Sacrifice]
Parameter 0 mg/kg/day 50 mg/kg/day 150 mg/kg/day 450 mg/kg/day
RBC 8.04 1 0.41C 10) 7.72 ± Q.49( 10) 7.69 ± 0.40C 10) 7.65 1 0.36< 10)
U 10*6/11111*3)
HGS 15.3 t 0.4( 10) 15.2 i 0.6{ 10) 15.2 * 0.6( 10) 15.1 * 0.5C 10)
HCT 42.4 ± 1.3( 10) 41.6 t 2.4( 10) 41.7 ± 2.U 10} 41.2 i 1.7( 10)
PT 12.7* Q.7C 10) 12.1 t 0.7( 10) 12.3 ± 1.4( 10) 11.4 t 0.9{ 10)
(sec.)
APT! 33.7 * 2.2(10) 31.41 7.4(10} 33.8 t 3.2(10) 33.0 ± 2.3(10)
(sec.)
RITIC 0.9 t 0.7( 10) 1.1 ± 0.7< 10) 1.1 t 0.51 10) 0.6 * 0.5C 10)
(% rbc)
WBC 13.5 ± 2.8( 10) 14.1 * 3.7< 10) 11.9 ± 2.6( 10) 13.5 i 2.7{ 10)
U 10*3/nm*3)
SEGS 2.2 ± 1.3< 10) 3,4 t 2.2( 10) 2.3 ± 1.4( 10) 2.7 ± 1.1< 10)
(x 10*3/wn'3j
BANDS 0.0 i O.Q{ 10) 0.0 t O.K. 10) 0.1 ± 0.1( 10) • fl.Q t 0.1( 10)
(x 10*3/1*11*3}
LWHS 11.1 1 2.9C 10) 10.2 ± 2.8( 10) 9.5 t 1.8C 10) 10.5 t 2.1( 10)
(x 10*3/mn*3)
HOMO 0.1 1 0.2C 10) 0.2 s 0.2C 10) 0.0 £ O.H 10)" 0.2 t O.U 10)
(x ^"S/irafS)
EOS 0.0 * 0.0< 10) 0.2 1 O.H 10)* 0.0 s 0.1( 10) 0.1 ± 0.1C 10)
Cx 10*3/ntn*3)
Statistically significant difference from control srouP
using ANOVA and Dunnett's T-Test (P«=Q,05).
Results presented as mean t standard deviation < N )
f)
-V
19
-------
Study Ho. 5221.07
TABLE 9
SUBCHRONtC TOXICITT OF HETA-CRESOl 1H SPRAG'JE DAWLEY RATS
MALE HEHATQLGGY VALUES
[Terminal Sacrifice]
Parameter 0 mi/kg/day 50 mg/kg/day 150 mg/kg/day 450 mg/kf/day
RiC I. 91 * 0.33C 10) 8.70 ± 0.27( 10) 9.09 ft O.i0< 9) 8.67 s 0.34C 10)
HG3 15.7 i 0.5C 10) 15.4 t 0.4< 10) 16.4 t 0.6< 103* 15.7 ± 0.5{ 10)
(g/dl)
HCT 43.9 t 1.2C 10) 43.0 ± 1.5C 10) 46. Q * 1.7C 10)* 44.4 ± 1.6( 10)
PT 11.3 t 1.7( 10) 11.4 t 2.2< 10) 12.2 * 1.7( 10) 12. 0 t 1.4( 10)
(stc.)
APTT 32.7 t 6.8( 10) 34.8 ± 1.8C 10) 36.0 * 3.9C 10) 35.9 i 5.4( 10)
(sec.)
RETIC 0.8 ± 0.3< 10) 0.6 t Q.3< 10) 0,6 i 0.5< 10) 0.8 t 0.6< 10)
(X rbc)
W8C 12.5 i 3.0< 10) 12.9 ± 2.5( 10) 11.7 ± 1.8< 10) 12.0 t 2.9C 10)
(x 1
SEGS 2.3 ± 1.1C 10) 2.4 t 1.3< 10) 2.2 t 1.7( 10) 2,2 ± 1.5( 10)
Csc 1Q*3/ram*3)
BANDS 0.1 i 0.2( 10} 0.1 i 0.1< 10) 0.1 ± O.K 10) 0.1 ± O.K 10)
(x 10'3/mm-3)
LYMPHS 9.8 * 2.6< 10) 10.2 t 1.4< 10) 9.2 ± 1.4( 10) 9.6 i 2.8( 10)
HOMO 0.1 ± 0.1( 10) 0.1 t 0.2< 10) 0.2 i 0.2< 10) 0.1 t 0.2C 10)
(x 1
EOS 0.1 ± 0.1C 10) 0.1 ± O.K 10) 0.1 i O.K 10) 0.1 i O.K 10)
(x 10*3/^3)
* •• Statistically significant difference from control group
using ANOVA and Dunnett's T-Test
-------
Study No. 5221.07
TABU 10
SUSCHRONIC TOXICm OF META-C8ESQL IN SPRAGUE DAULEY SATS
FEMALE HEMATQLCGY VALUES
[Interim Sacrifice]
Parameter 0 mg/kg/day 50 ng/kg/day 150 mg/kg/day 450 mg/kg/day
RSC 7.72 i 0.30( 10) 7.66 * 0.37C 10} 7.83 i 0.43{ 8) 7.36 t 0.45( 9)
(x 10*6/nm*3)
HGB 15.4 t 0.5( 10) 15.5 ± 0.6< 10) 15.8 i. 1.0( i) 15.1 t 0.4( 9}
Cg/dl >
HCT 41. 6 t 1.7( 10) 42.2 t 1.8( 10} 43.3 i 2.3< 8) 41.1 i 1.7( 9}
PT 10.9 t 1.5C 93 11.4 t 2.0< 10) 11.3* 0.8(10) 10.9 i 1.9(10)
(see.)
APTT 32.5 ± 5. OC 9) 38.0 ± 9.2C 10) 33,9 t 3.5( 10) 37.4 t 7.3( 10)
(x 1
' SEGS ' 2.0 t 1.2C 10) 2.1 i 1.2(10) 1.S1 1.0( 8) 2.4 t 1.4( 9}
(x 1
SANDS 0,0 t O.H 10) 0.1 * 0.2( 10) 0,0 4 0.1( 1) 0.0 i 0.0( 9)
-------
Study No. 5221.07
TABLE 11
SUSCHRONIC TOXieiTY OF KETA-CRESOL IN SPRAGUE DAULEY RATS
FEMALE HSMATOLOGY VALUES
[Terminal Sacrifice]
Parameter 0 nig/kg/day 50 mg/kg/day 150 mg/lcg/day 450 mg/kg/day
RBC 8.23 ± 0.35{ 10} 8.47 i 0.46C 10) 8.50 ± 0.2/C 10) 8.30 * 0.54< 10)
(x 10A6/mmA3)
HG3 15.5 ± Q.6C 10) 15.9 t 0.7< 10) 16.2 t 0.4< 10) 15.6 t 0.8C 10)
(g/dl)
HCT 44.0 * 2.3C 10) 44.7 * 2.0C 10} 45.8 i 1.8( 10) 44.5 * 2.8< 10)
(X)
PT 11.2 i 0.9< 10) 11.1 t 1.8( 10) 1Q.9s 1.9( 10) 10.9 t 1.3( 10)
(see.)
APTI 33.9 ± 7.5{ 10) 37.8 ± 5.1( 10) 36.6 i 4.3< 10) 36.6 * 2.6{ 10)
(sec.)
R£T!C 0.7 i 0.5( 10) 0.6 ± 0.3C 10) 0.8 s 0.6< 10) 0.6 t 0.4< 10)
(X rbc)
UBC 8.7 t 1.8C 10) 9.4 ± 2.6{ 10) 9.3 ± 2.2< 10) 8.6 t 2.7{ 10)
Cx 10*3/nw"3)
SEGS 1.4 i 0.7C 10) 1.6 * 1.1{ 10) 1.3 t 0.7C 10) 1.4 i 1.1C 10)
(x 10A3/mmA3)
BANDS 0.0 ± 0.1< 10) 0.1 ± 0.1( 10) 0.1 i 0.1( 10) 0.1 1 0.1( 10)
Ix 10'3/ran"3)
LYMPHS 7.0 i 1.4( 10) 7.5 t 2.1( 10) 7.8 * 2.6( 10) 6.9 t 2.3< 10)
(x ia*3/itm"3)
MONO 0.1 t 0.2( 10) 0.1 t Q.1C 10) 0.1 t 0.1( 10) 0.1 t 0.1( 10)
(x 10'3/rnra*3)
EOS 0.1 ± O.K 10) 0.1 t 0.1C 10) 0.1 * O.K 10) 0.2 i O.lC 10)
(x 1
Results presented as mean t standard deviation CM)
26
22
-------
Study No. 5221.07
TABLE 12
SUBCHRONIC TOXICITT OF META-CRESOL IN SPRAGU1 DAWLEY RATS
MALE CLINICAL CHEMISTRY VAIUES
[Interim Sacrifice!
Parameter 0 rag/kg/day 50 mg/kg/day 150 mg/kg/day 450 mg/leg/day
GLU 249.2* 72.4( 93 240.11 89.5(10) 257.2* 85.4(10) 221.4* 88.4(10)
(mg/dt)
BUN 17,8 t 3.1< 9) 16.0 * 2.4( 10) 17.8 * 3.7( 10) ' 16.0 i 3.QC 10}
(rng/dl)
SGPT 27 t 5( 95 55 t 79C 10) 27 i 7( 10) 33 i 13< 10)
Ctu/l)
SCOT 74 t 17{ 9} 116 i 136( 10) ' 67 i 19C 10) 86 t 23( 10)
(lu/L)
T PRO 7.5 t 1.1C 9) 7.2 ± 0.8< 10) 7.3 ± 0.8C 10) 6.8 t 0.7( 10)
(g/dl)
AL3 3.9 ± 0.5C 9) 3.8 ± 0.4C 10) 3.9 i 0.4( 10) 3.6 * 0.2( 10)
(g/dl)
GLOB 3.6 * 0.6{ 9) 3.4 t 0.5( 10) 3.5 ± 0.5( 10) 3.2 ± 0.5C 10)
(g/dl)
ALB/GLOB 1.106 t 0.097{ 9) 1.121 t Q.076( 10) 1.127 t 0.084C 10) 1.131 t 0.104( 10)
(ratio)
CHQL 75.3 i 10.DC 9) 74.9 i 16.4( 10) 81.9 t 18.9( 10) 72.7 t 11.9( 10)
(ma/dl)
Results presented as mean t standard deviation ( N >
23
-------
Study No. 5221.07
TABLE 12 (continued)
SUBCHRONIC TGXtCITY OF NETA-CRESOL 1« SPRAGUE DAWLEY RATS
HALE CLINICAL CHEMISTRY VALUES
[Interim Sacrificel
Parameter 0 mg/kg/day 50 mg/kg/day 150 mg/kg/day 450 mg/kg/day
D I1L 0.02 t Q.QK 9) 0.03 i 0.03C 10) 0.03 ± 0.02C 10) 0.02 i Q.Q2C 10)
K 11.7 i 2.7t 9) 10.2 i 4.7( 10) 10.2 i 2.1< 9) 9.6 ± 2.9C 10)
(Heq/l)
Cl 100 i 3C 9) 103 ± 2( 10) 101 t 1C 9) 99 i 8( 10)
-------
Study Mo. 5221.07
TA8LI 13
SUBCHRQN1C TQXtCITY OF META-CRESOL IN SPRASUE DAU16Y RATS
HALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
Parameter 0 mg/kg/day 50 mg/kg/day 150 rag/kg/day 450 mg/kg/day
GLU 223.7 t 43. 9( 10) 229.2 * 40. 9C 10) 241.2 t 47.61 10) 233.3 t 33. 8< 10}
(mg/dU
BUM 13.3 t 2.3( 10) 13.5 ± 2. 1C 10) 14.0 ± 2.7< 10) 13.9 i 2.2C 10)
(mg/dl)
SGPT 28 i 5( 9) 27 * 3C 10) 40 * 22( 10) 31 t 6C 10)
Clu/l)
SCOT 76 * 12< 10) 73 ± 8C 10) 97 * 22( 10)* 86 i 20C 10)
(lu/l)
T PRO 6.7 i 0.4< 10) 6.7 t 0.7( 10) 7.1 * 0.6< 10) 6.6 ± 0.8( 10)
Ci/dl)
ALB 3.8 i 0.2( 10) 3.9 i 0.2C 10" 4.1 t 0.5< 10) 3.9 i 0.3( 10)
GL08 2.9 * 0.4C 10) 2-8 t 0.6< 10) 3.1 i 0.5( 10) 2.7 ± 0.7( 10)
(g/dl)
ALB/CLOi 1.362 s 0.238< 10) 1.441 * 0.327C 10) 1.382 ± 0.333C 10) 1.561 ± 0.495C 10)
(ratio)
CHOI 57.2 * 12. K 10) 64.7 t 18, 1C 10) 66.4 * 18. 0{ 10) 59.1 i 11. 4C 10)
(mg/dl)
* •- Statistically significant difference from control group
using AMOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean ± standard deviation { N )
25
-------
Study No. 5221.07
TA8L1 13 {continued)
SUSCHRQN1C TDXIC1TY OF META-CRESOL IN SPRAGUE DAWLEY RATS
MALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
Parameter 0 mg/kg/day 50 nig/kg/day 150 mg/kg/day 450 mg/kg/day
D BIL 0,02 i 0.03C 10) 0.02 * 0.03< 10) 0.02 ± 0.02C 10) 0.05 t 0.08C 10)
(mg/dt)
T BIL 0.14 t 0.04C 10) 0.15 t 0,04( 10) 0.16 i Q.07< 10) 0.15 t Q.Q4C 10)
(mg/dl)
Ca 9.8 t 2.2{ 10) 10.6 ± 2.2( 10) 9.4 t 1.9( 10) 9.8 ± 1.8( 9)
(mg/dl)
Na 146 t 2{ 7) 144 i 3( 8) 145 t 2C 7) 146 i 3( 6)
(Meq/1)
K 6.2 ± 0.7( 7) 6.1 t 1.1C 8) 6.8 t 1.6< 7) 6.6 i 0,9{ 6)
(Meq/L)
Ct 103 i K 7) 102 t 1C 8) 102 s 2C 7; 103 s 2< 6)
(Heq/l)
ALK PHOS 62 t 21C TO) 87 i 26< 10) 66 t 23< 10) 88 i 25< 10)
(lu/t)
C02 24 ± 4( 7) 23 i 4( 8) 25 i 5( 7) 23 * 7( 6)
(Meq/l)
CREAT 0.67 t 0.17( 8> 0.73 t 0.10C 10) 0.78 i 0.09< 10) 0.78 i 0.14< 8)
(mg/dl)
PHOS 8.5 i 0.7C 71 8.3 ± 1.1( 8) 7.9 ± 1.2( 8) 8.8 t 0.5( 8)
* -• statistically significant difference from control group
using ANQVA and Dunnett's T-Test
-------
Study No. 5221.07
TABLE 14
SUBCHROHIC TQXiCITf OF META-CRESOL JM SPRAGUE DAWLEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
Clnterim Sacrifice]
Parameter D mg/kg/day 50 mg/kg/day 150 mg/kg/day 450 mg/kg/day
GLU 204.8 i 69. 4( 103 212.0 * 71. 6< 10) 186.7 ± 74. 3( 10} 230.3 ± 122. 2< 10}
(mg/dl)
SUM 19.6 ± 2.3{ ID) 19.6 ± 4.2< 10) 21.6 ± 4.0< 10) 19.5 i 3.1J 10)
Cng/dl)
SCPT 29 i 10( 10) 34 i 9( 10) 34 1 11< 9) 36 i 16( 10)
SGOT 79 i 12{ 10) 77 1 11{ 10) 75 i 12( 9) 81 ± 22( 10)
(IK/I >
T PRO 7.5 t 0.9( 10) 8.0 i 1.0< 10) 7.8 t 1.1< 10) 7.8 t 1.3< 10)
(g/di)
ALB 4.2 t 0.5{ 10) 4.5 1 0.7( 10) 4.3 t Q.5( 10) 4.2 .• 0.6C 10)
(S/dl)
GL01 3.3 i 0.6( 10) 3.5 t 0.5{ 10) 3.5 i 0.6( 10) 3.6 i- 1.Q{ 10)
ALB/GLOB 1.309 t 0.208( 10) 1.305 1 0.149C 10) 1.250 t 0.136C 10) 1.242 * 0.266{ 10)
(ratio)
CHOI 99.7 i 13. 5( 10) 100.5 * 18. 9< 10) 100.2 * 22. 6( 10) 115.4 i 31. 5( 10)
(mg/dl)
Results presented as mean i standard deviation CM)
27
-------
Study Ho. 5221.07
TABLE 14 (continued)
SUBCHRON1C TOX1CITY OF HETA-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Interim Sacrifice]
Parameter 0 mg/kg/day 50 rag/kg/day 150 mg/kg/day 450 mg/kg/day
D Bit 0.03 i Q.02C 10) 0.04 i 0.03{ 10) 0.03 1 0.03< 10) 0.04 t O.D3( 10}
(rag/dl)
T 81L 0.15 ± 0.04C 10) 0.16 i 0.05( 10) 0.1? 1 O.Q4C 10) 0.18 i 0.05C ,10)
(rag/dl)
Na 151 i 12C 8) 158 i 20C 8) 151 i 12{ 6) 152 t 13( 8)
CMeq/l)
K. 13.2 ± 5.0< 85 10.5 t 1.3C 73 15.1 ± 3.4( 6) 12.2 ± 2.5( B)
(Heq/l)
Cl 108 i 9( 8) 111 ± 19? 8) 111 * 15C 63 107 t 13C 8)
(Heq/l)
ALK PHOS 54 ± 18( 103 47 i 15( 10) 54 4 18< 10) 51 t 18{ 10)
(lu/l)
C02 17 i 5< 8) 19 t 7( 8) 14 * 3( 6) 19 i 5( 83
CMtq/t)
CREAT 0.71 t Q.19C 10) 0.77 t Q.Q7C 10) 0.72 t 0.15( 103 0.86 i 0.10C 10)
.
Results presented as mean i standard deviation ( N )
28
-------
Study No. 5221.07
TABU 15
SUBCHRONIC TOXICm OF HETA-CRESQL IN SPRAGUE DAWLEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
0 itB/ka/day _ 50 mg /kg/day _ 150 mg/ kg/day _ 450 mg/kg/day
GLU 215.7 i 36.0 (10) 204. 0 ± 29.4 (10) 199.1 * 51.2 (10) 206. 5 1 57.2 CIO)
BUN 16.1 ± 4.1 (10) 14.6 i 2.9 (105 15.6 ± 3.5 (10) 14.3 t 3.2 (10)
(mg/dl)
SSPT 38 i 20 (10) 33 i 11 (10) 26 ± 5 (10) 33 i 11 (10)
SGOT 103 t 38 (10) 85 1 8 (10) B2 t 16 (10) 83 t 17 (10)
T PRO 7.3 t 0.7 (10) 7.4 * 0.6 (10) 7.2 t 0.6 (10) 7.2 + 0.7 (10)
ALB 4.5 t 0.5 (10) 4.3 ± 0.4 (10) 4.4 t 0.4 (10) 4.5 t 0.4 (105
cg/di)
GLOB 2.B t 0.4 (10) 3.0 ± 0.4 (10) 2.7 * 0.5 (10) 2.7 i 0.5 (10)
(i/dO
ALB/GLC8 1.603 ± 0.260 (10) 1.467 ± 0.260 (10) 1.674 i 0.435 (10) 1.775 t 0.468 (10)
(ratio)
CHOI 85.5 i 12.8 (10) 77.4 ± 14.2 (10) 69.9 t 15.8 (9) 81.3 t 16.5 (10)
(mg/dl 5
Results presented as mean i standard deviation ( N )
29
-------
Study No, 5221.07
TABLE 15 (continued)
SUBCHROMIC TOXICITY OF META-CRSSOL IN SPRAGUE DAULEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
_ 0 mg/kg/day _ 50 ing/kg/def _ 150 mq/kg/dav _ 450 mg/kg/day
D BIL 0.01 ± 0.01 (10) 0.03 ± 0.05 (10) 0.01 t 0.02 {10) 0.05 * 0.08 (10)
T BIL 0.15 ± 0.06 (10) 0.15 ± 0.11 £10) 0.16 ± 0.04 (103 0.14 ± 0.07 (10)
Ong/dl)
Ca 11.3 t 2.1 (10) 10.8 ± 1.6 (10) 10.9 ± 1.3 (10) 11.1 * 1.3 (10)
(mg/dt)
Na 144 t 2 (6) 145 t 3 (8) 145 ± 5 (7) 143 * 3 <6>
(Heq/l)
K 7.2 ± 1.1 (6) 7.0 i 1.1 (8) 7.7 i 1.4 (7) 7.4 ± 1.0 <6)
(Heq/l)
Cl 103 t 3 (6) 103 t 2 (8) 104 i 3 (7) 104* 3 (6)
(Meq/l)
ALK PHOS 51 ± 18 (10) 71 * 70 (10) 53 i 17 <10) 76 t 43 (10)
CQ2 18 t 4 <6) 23 t 6 (8) 19 i 3 (7) 19 t 3 (6)
(Meq/D
GREAT 0.77 * 0.08 (10) 0.76 i 0.17 (10) 0.75 * 0.08 (10) 0.74 ± 0.11 (10)
Cmg/dl)
PKOS 8.0 t 0.8 (9) 7.6 i 1.2 (9) 7.8 t 1.2 (10) 8.3 s 0.8 (9)
(mg/dl)
Results presented as mean t standard deviation ( M )
? A
30
-------
Study No. 5221.07
TAiLE 16
SU8CHRQNIC TOXICSTt OF HETA-CRESCL IN SPRAGUE DAWIEY RATS
RELATIVE HALE ORGAN WEIGHT DATA (X Terminal Body Weight)
tTerminal Sacrifice]
Organ
HEART
LIVER
SPLEEN
KIDNEY-LF7
KIDNEY-R1
TESTIS-LFT
TESTIS-RT
ADRENALS
BRAIN
THY. /PARA.
0 mg/kg/day
0.327 t
3.313 t
0.148 ±
0.370 ±
0.380 t
0,338 i
0.339 i
0.014 i
0.409 ±
0.008 i
0.028(
0.339C
0.01K
Q.038C
0.036(
0.073C
0.090(
0.004C
Q.Q35C
O.Q05C
20)
20)
20}
2Q>
20)
20)
205
20)
20)
20)
50
0.338
3.327
0.144
0.360
0.365
0.318
0.315
0.013
0.412
o.o-:?
mg/kg/day
t 0.037<
t 0.3Q1C
± 0.02QC
i O.Q47C
t 0.041C
i 0.032<
1 0.029C
t 0.002C
t 0.034C
t 0.002(
20)
19)
203
20)
20)
20)
20)
20)
20)
20)
ISO mg/kg/day
0.347 4
3.121 s
0.141 t
0.387 ±
0.385 1
0.339 t
0.345 t
0.014 i
0.447 i
0.006 i
0.033C
Q.349C
0.024<
0.040C
0.045C
0.048C
0.03K
O.QQ3C
0.042C
0.002.C
20)
20)
20)
20)
20)
20)
20)
20)
203*
20)
450 mg/kg/day
0.355
3.412
0.155
0.386
0.397
0.360
0.368
0.015
0.476
0.007
i 0.042? 19)
t Q.358C 19)
± 0.024C 19)
i 0.067( 19)
i 0.068C 19)
i 0.033{ 19)
i 0,050( 19)
t 0.004C 19)
t 0.057C 19)*
t Q.QQ3C 19)
* •- Statistically significant difference from control group
using ANOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean i standard deviation ( N )
31
Q ^
O w
-------
Study Ho. 5221.07
TABLE 17
SUSCHRONIC TOX1CITY OF META-CRESOL IN SPRAGUE QAWIEY RATS
RELATIVE FEMALE ORGAN WEIGHT DATA
-------
Study No. 5221.07
TABLI 18
SUBCHRON1C TOXSCITY OF KETA-CRESOL IN SPRAGUE OAWLEY RATS
KALE ORGAN WEIGHT DATA {3}
[Terminal Sacrifice]
Organ
HEART
LIVER
SPLEEN
KIDNEt-LFT
KIDNEY-RT
TESTIS-LFT
TEST1S-RT
ABRENALS
BRAIN
THY, /PARA.
0 mg/ks/day
1,811 ±
18.344 i
0.819 ±
2.047 ±
2.094 i
1.859 i
1.863 ±
0.075 ±
2.250 t
0.042 4
0.205C
2.49S<
0.104(
Q,239(
0.19Q(
0.377C
0.47K
0.019(
0.084C
0.020C
20)
20)
20)
20)
20)
20}
20)
20)
20)
20)
50 mg/kg/day
1.858 i
18.181 ±
0.790 i
1.975 t
2.003 ±
1.741 t
1.724 t
0.072 t
2,238 t
0.036 i
Q.214C
1.6S7{
0.1 27(
0.259C
0.233C
0.132C
0.116C
0.015(
0.082(
O.OQ9(
20)
19)
20)
20)
20)
20)
20)
20 >
20)
20}
150 mg/kg/day
1.764 ±
15.928 t
0.716 t
1.968 1
1.959 t
1.717 t
1.751 t
0.070 t
2.265 i
0.031 ±
0.167C
2.351C
0.122C
0.188C
0.229C
0.177C
0.096(
0.013C
0.098(
O.QOJC
20)
20)*
20}*
20)
20)
20)
•20)
20)
20)
20)
450 rag/kg/day
1.705 1
16.408 t
0.743 *
1.849 t
1.897 1
1.717 t
1.760 t
0.072 t
2.272 t
0.035 t
0.240C 19)
2.367( 19)*
0.127( 19}
0.341 ( 19}
0;331( 19)
0.091( 19)
C.262C 19)
0.019< 19}
0.181( 19)
Q.Q12C 19)
Statistically significant difference from control group
using ANOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean i standard deviation { N )
33
-------
Study Ho. 5221.07
TABLE 19
SUBCHRONIC TOXIC1TY OF HETA-CRESOL IM SPRAGUE DAyLEY RATS
FEMALE ORGAN UEIGHT DATA Cg)
[Terminal Sacrificel
Organ
HEART
LIVES
SPLEEN
K1DNEY-LFT
KIDNEY-RT
OVARY -I FT
OVARY -RT
ADRENALS
BRAIN
THY. /PARA.
0 mg/kg/day
1.107 s
9.093 4
0.541 i
1.050 t
1.098 ±
0.073 i
0.074 ±
0.072 ±
2.078 ±
0.026 ±
0.210(
0.949<
Q.OS9(
0.10S(
0.080C
Q.Q10C
0.01U
o.oia<
0.102C
0.009(
20)
20)
20)
20)
20)
20)
20)
20)
20}
20)
50 mg/kg/day
1.065 i
9.192 t
0.542 t
1.024 i
1.053 i
0.089 t
0,082 i
0.081 *
2.073 i
• 0.030 i
0.109C
1.287C
0,077(
0.122C
0.102C
0.019{
0.019C
0.017C
0.079C
0.013<
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
150 mg/kg/day
1.063 t
9.229 t
0.514 t
1.166 t
1.115 ±
0.081 t
0.081 ±
0.075 ±
2.063 i
0.027 t
0.164<
0.938C
0.075C
Q.4Z2(
O.OB2(
0.029{
0.017(
Q.Q14C
0.093C
0.006C
20)
19)
20)
19)
18)
20)
20)
20)
20)
20)
450 mg/kg/day
0.99S i
9.092 i
0.486 4
1.032 t
1.077 t
0.075 i
0.079 t
O.Q69 t
2.013 i
0.025 *
0.103C 20)
1.373< 20)
0.089( 20)
0.1C6( 20)
0.12BC 20)
0.022C 20)
0.025( 20)
0.015( 20)
0.106C 20)
0.005{ 20)
Results presented as mean i standard deviation { H )
-------
Study No. 5221.07
Table 20
Subchronic Toxic ity Study of
Meta-Cresol in Sprague Dawley Rats
Male Hematology
Baseline Values
ANIMAL
BBC
HGB
HCT
MCV
MCH
MCHC
KEIXC
0 mg/kg
3521
3522
3523
3524
3525
3526
3527
3528
3529
3530
MEAN
STD
5.80
6.46
6.66
6.06
6.29
6.97
5.96
6.65
6.71
5.33
6.29
0.50
13.2
13.7
15,1
13.2
13.9
14.6
13.3
14.7
14.0
12.0
13.8
0.9
37.5
40.2
43.2
39.2
40.6
44.4
39.1
43.3
41.3
35.1
40.4
2.8
- 65
62
65
65
65
64
66
65
62
66
65
1
22.8
21.2
22.7
21.8
22.1
20.9
22.3
22.1
20.9
22.5
21.9
0.7
35.2
34.1
34.9
33.7
34.2
32.9
34.0
33.9
33.9
34.2
34.1
0.6
1.0
0.8
0.1
0.1
0.3
0.4
0.6
2.0
1.0
1.4
0.8
0.6
Subchronie Tcxicity study of
Meta-Cresol in Sprague Dawley Rats
Female Hematology
Baseline Values
ANIMAL
SBC
HGB
HCT
MCV
MCH
KCHC
RSJTC
0 rag/kg
3651
3652
3653
3654
3655
3656
3657
3658 '
3659
3660
MEAN
STD
6.65
6.01
5.92
6.29
5.29
5.54
6.41
'7.18
5.98
6,56
6.18
0.55
13.9 .
13.3
12.8
13.4
12.0
12.6
13.3
14.2 •
12.6
13.3
13.1
0.7
41.1
39.4
36.6
37.1
35.0
36.0
38.6
41.7
36.8
38.3
38.1
2.2
62
66
62
59
66
65
60
58
62
58
62
3
20.9
22,1
21.6
21.3
22.7
22.7
20.7
19.8
21.1
20.3
21.3
1.0
33.8
, 33.8
35.0
36.1
34.3
35.0
34.4
34.0
34.2
34.7
34.5
0.7
0.2
0.3
0.3
0.1
0.8
0.1
0.1
0.1
0.1
0.2
0.2
0.2
35
9
*>
-------
Study No. 5221.07
Table 20 {continued)
Subchronie Toxicity Study of
Meta-Ctesol in Sprague Dawley Eats
Male Hematology
•Baseline Values
ANIMAL
•WBC
SEGS
BANDS LYMEHS
MDNO
EOS
Subchronie Toxicity Study of .
Meta-Cresol in Sprague Dawley Rats
Female Hematology
Baseline Values
MIMAL
WBC
SBGS
BftNDS LBKFHS
MDNO
EOS
FT
AFTT
0 rog/kg
3521
3522
3523
3524
3525
3526
3527
3528 .
3529
3530
MEM
STD
9.4
13,0
15.7
14.4
11.7
13.1
11.8
15.8
17.7
9.3
13.2
' 2.8 .
22
44
11
9
5
3
15
13
19
15
16
.11
0
0
2
0
0
1
0
1
0
1
1
1
76
" 48
77
87
95
85
84
83
79
83
80
12
2
3
6
4
0
4
1
2
1
0
2
2
0
0
0
0
0
1
0
0
1
0
0
0
10.8
11.0
11.5
10.8
11.2
11.1
10.8
11.0
9.6
8.0
10.6
1.0
25.7
24,0
33,5
17.1
36.0
24.9
18.1
35.7
22.9
32.8
27.1
7.0
MTT
0 mg/kg
3651
3652
3653
3654
3655
3656
3657
3658
3659
3660
MEAN
STD
11.2
10.9
11.5
9.0
7.2
11.5
8.7
5.4
11.4
9.1
9-6
2.1
6
2
10
8
3
6
4
13
2
9
6
4
0
2
2
0
0
0
0
0
0
0
0
1
92
89
85
84
92
86
93
82
93
88
88
4
0
7
2
7
5
7
2
3
4
3
4
2
0
0
1
1
0
1
0
0
0
0
0
0
10.8
10.8
10.8
11.2
10.7
10.9
10,6
10.5
10.6
10.6
10.8
0.2
28.9
28.9
22.2
25.7
19.1
40.5
31.0
38.6
27.7
30.5
29.3
6,6
36
-------
Table 21
Subchronie Toxicity Study of
Meta-Cresol in Sprague Dauley Rats
Male Clinical Chemistry
Baseline Values
Study No. 5221.07
ANIMAL
TPRO
BALB
GLOB
BUN
CREA
GLUC
FBIL
DBIL
AST
ALT CHOL
ALP
PHOS
NA
CL
C02
0 mg/kg
3521
3522
3523
3524
3525
3526
1 3527
3528
3529
3530
HEAN
STD
5.7
6.0
5.9
6.0
6.7
6.7
6.4
6.1
6.2
6.Z
6.2
0.3
3.9
4.1
3,9
4.0
4.3
4.3
4.2
4.0
4.0
3.8
4.1
0.2
1.8
1.9
2.0
2.0
2.4
2.4
2.2
2.1
2.2
2.4
2.1
0.2
16.1
Z0.4
16.7
16.9
20.9
21.4
24.3
18.0
19.1
Z3.4
19.7
2.8
0.83
0.82
0.67
0.78
0.73
0.78
0.71
0.79
0.73
0.69
0.75
0.05
185.7
354.0
267.2
426.1
283.6
422.6
242.4
335.4
316.4
344.9
317.8
76.0
0-36
0.26
0.30
0.29
0.28
0.27
0.30
0.27
0.25
0.27
0.29
0.03
0,15
0.12
0.10
0.11
0.09
0.15
0.14
0.12
0.17
0.04
0.12
0.04
96
95
88
86
81
91
84
89
73
79
86
7
35
40
50
40
36
50
32
39
32
29
38
7
60.6
55.3
51.6
BO. 2
55.9
105.2
62.4
74.0
80.9
76.0
70.2
16.4
188
411
345
247
229
266
369
280
185
178
270
82
14.4
11.2
12.4
15.0
13.2
14.8
12.2
14.4
13.0
13.6
13.4
1.2
QNS
11.0
QNS
12.1
8.7
12.5
9.3
12.0
8.8
12.4
8.7
4.8
QNS
144
QNS
145
142
148
146
144
145
142
116
61
QNS
113
QNS
120
113
105
109
106
106
107
aa
47
18
21
15
25
26
21
28
19
26
22
22
4
-------
Table 21 (continued)
Subchronic Toxicity Study of
Meta-Cresot in Sprague Dawley Rats
Female Clinical Chemistry
Baseline Values
Study No. 5221.07
ANIMAL
TPRO
BALB
GLOB
BUN
CREA
GLUC
TBIL
DB1L
AST
ALT
CHOL
ALP
PHOS
NA
CL
C02
0 mg/kg
3651
5652
3653
3654
3655
3656
3657
on 3658
3659
3660
MEAN
STD
6.0
5.9
6.4
6.4
6.4
5.8
6.5
6.9
6.6
6.7
6.4
0,4
4.2
4.3
4.4
4.4
4.4
4.1
4.5
4.9
4.9
4.7
4.5
0.3
1.8
1.6
2.0
2.0
2.0
1.7
2.0
2.0
1.7
2.0
1.9
0.2
16.6
20.3
18.6
19.2
24.3
21.3
18.9
20.5
27.0
18.1
20.5
3.1
0.64
0.62
0.61
0.71
0.71
0.67
0.68
0.75
0.70
0.64
0.67
0.05
312.1
258.2
287.3
212.9
389.3
325.5
376.8
345.3
315.8
364.3
310. 8
54.9
0.2%
0.30
0.26
0.29
0.33
0.21
0.21
0.21
0.19
0.27
0.25
0.05
0.11
0.16
0.08
0.05
0 09
0.02
0.17
0.02
0.16
0.13
0.10
0.06
63
71
76
84
88
66
70
93
88
80
78
10
33
35
34
40
41
29
30
29
37
26
34
5
74.9
56.0
56.3
81.6
76.7
68.2
86.0
72.5
76.5
63.9
71.3
10.1
279
330
340
185
305
196
169
181
394
158
254
86
13.0
11.6
13.6
12.8
15.6
11.4
12.6
15.6
16.6
14.8
13.8
1.8
10.5
7.6
10.4
8.9
14.1
11.5
11.4
13.7
10.7
QMS
9.9
4-0
143
143
140
148
149
144
140
147
141
QMS
130
46
109
109
107
105
104
107
108
107
104
QMS
96
34
26
26
20
25
22
19
19
14
22
QMS
19
8
-------
Exoeriment Numbar 5221.07
SUBCHRONIC TOXICTTY OF MEIA-CRE50L IN
SERAGUE DAWLEY RATS
I. FURPCgS
The purccse of this study is to determine the toxic effects of
m-cresol when administarad by gavage for 13 weeks to Sprague Dawley
rats.
II. SPONSOR AND TESTING FACILITY
A- Sccrsor Name; Research Triangle Institute (HIT)
B. Sponsor Authorization Date: (See last page)
C. Protocol Approval Date: (See last page)
D. Testing Facility: Microbiological Associates Inc.,
5221 River Read
Bethesda, Maryland 20816
E. Princirial Investigator (Study Director): Lcuis T. Milligan, Ph.D.
F. Toxicolocist: Barry S. Levine, D.Sc., D.A.B.T.
IH. TEST SCHEDULE
A. Scheduled Initiation Pats: 26 Septsmfcer 1985 :
B. Frcncsad Termination Date: 26 December 1335
43
-------
Number 5221.07
IV. TEST ASTICIS
A. Name: m-cresol
B. Source and Manufacturar
Source: Eastman Kodak Camcany
Rochester, NY 14650
Manufacturer: To be supplied
1st No.: K-14-A
Batch No.: None
Purity: 99% +
In-house Chemical No.: 24
C. Safety _Prscauticns
1. Personnel_ Protection
Eye: Safety goggles
Gloves: Two pairs of gloves should be worn when
handling the neat chemical; one pair of
gloves should be worn when handling dose
preparations.
Clothing: Protective laboratory clothing will be
worn when handling doss preparations or
neat chemical.
Ventilation: Handling of cpen dosage containers
or chemical should be conducted in a
properly vented heed.
Respirator: A respirator fitted with an organic
. vapor (or organic vapor/acid vapor)
, cartridge equipped with a particulate
filter will be used at all times when
working with open containers and when
working in roans with animals dosed
with this chemical.
44
-------
E3
-------
Experiment Number 5221,07
5. Analysis of Solutions
The stability of the test solution will be determined
after storage for the same period and under the same
condition to be used in the study.
The accuracy of foomlation will be checked by analysis
of samples taken from solutions prepared for administration
during weeks I/ 2, 4, 8 and 13 of treatment.
V. TEST SYSTSg
A. Animals
1. Strain/Species: Sprague Dawley Rats
2. Number/Sex; 130 males/130 females
3. Age: 5-6 weeks old at start of dosing
4. Supplier: Charles River Breeding Laboratories
Laksview, NY
5. Justification of Test Animal: The test aniaal (Sprague
Dawley Eats) was specified by the sponsor and is a routine
laboratory animal utilized in small rodent subchrcnic toxicology
stoii.es.
VI. HOUSING
The animals will be individually housed in polycarbonate shoe boxes
narked with a test article code and held on stainless steel racks
equipped with, an automatic watering system. Heat treated hardwood
chips will be used for cage bedding. Backs will be periodically
repositioned within the room to •minimize any effect of variation in
light intensity/ teirperature, etc.
VH. ANIMAL ENVTHDNMEMT
A. Tertcerature: 72° ± 3°F
3. Humidity: 50 ± 15%'
C. Light Cycle: 12 hcur cycle
D. Water: Washington Suburban Sanitary Commission Fotor.ac
Plant; untreated; ad libitum.
E. Feed: Purina standard lab chew. , * e
4
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Experiment Number 5221.07
F. Cage Change Schedule; Cages will be changed every other week.
G. Feeder Change Schedule: Once weekly.
H. Rack Changes: Every ether week.
I. Air Change: At least 12-15 per hour.
J. Bedding Changes: Iwica weekly.
K. It is not expected that there are contaminants in the feed or
water which wculd have any influence on the study.
VIII. OTARAOTIKS
A. Animals will be maintained in quarantine for 12-16 days. The
cleaning, feeding and watering procedures will be the same as
described above for the test period. Animals will be group
housed during the quarantine period, but individually housed at
test animal selection.
B. Animals will be observed twice daily for signs of illness or '
death and all unusual observations will be reported to the Principal
Investigator or Director of Veterinary Medicine.
C. Animals will be examined' during quarantine and approved for use
by the Director of Veterinary Medicine prior to being placed on
test. Health Status Evaluation form RA/Q^ H will be completed
by the Study Director and Director of Veterinary Medicine.
XX. RANDOMIZATION, ANIMAL NUMBERING, STATISTICAL ANALYSIS
A. Randomization: Curing the quarantine period, the anunals will be
.randanized as'follows: Starting with one sex of the species to be
randomized, each animal will be weighed, placed into • individually
numbered cages and separated into one of a number of weight range
groups which are based on successive intervals of 5 grains. The
weight of each is recorded on paper. After all animals have been
placed into their appropriate weight range groups, 120 of the aniaels
with weights closest to the median weight will be randomized.
Outliers will be used for health check evaluation and baseline
evaluations or killed.
After the appropriate number of animals per sex have been selected,
a random nusber table will be oaipitar generated for each sex
and used to allocate animals to a treatment group.
-------
Experiment Number 5221.07
3. limbering; Animals will fce uniquely consecutively numbered using
tee clips.
C. Statistics: The data will be examined using analysis of variance
techniques followed by a multiple ccnparison procedure for detecting
- differences between pairs of leans. Seme pathology and clinical
data may require nonparametric techniques to aid in interpretation.
x. EgERiManaii METKOCS
A. Dosing
1. louts: Gavage (specified by sponsor)
2, Vehicle: Com Oil
3. Frequency: Daily, approximately the same time each day,
7 days a week, for a total period of 13 weeks.
4. Dosage Volume; Five (5) ml/kg calculated on animal's most: recent
body weight.
5. Controls: Receive vehicle alone at the saire dosage volxuna
as treated animals,
6. Mixing Frequency: Dosing solutions will be mixed on a weelcly
basis.
-------
ExDeriinent Number 5221.07
B. Treatment Groups
Animals will be randomly assigned to groups with the following
design:
Number of Animals
Cose Level
Group
1
2
3
4
5
Treatment
Negative control
m-cresol
m-cresol
m-cresol
Baseline clinical
dna/ka/dav)
50
150
450
___
Male
30
30
30
30
10
Feipale
30
30
30
„ - 30
10
pathology
The tan male and tan female animals in grcup #5 will be sacrificad
at study initiation for collection of baseline data on heratolcgy
ard serum chemistry.
Ten male and-ten female animals (selected prior to initation of
the study) frcm each remaining group will be sacrificed at 45-days
pcst-treataent initiation for clinical pathology and collection
of tissues for pcssbile later evaluation. The following organs
will be weighed: heart, liver, spleen, brain, kidneys (individually),
gonads (individually), adrenals and thyroid/parathyroid.
C. Clinical Observations
1. Animals will be observed twice daily (once in the morning ard
once in afternoon) seven days per week for ircribundity/mDrtality,
Moribund animals unliScely to survive until the next observation
will be sacrificed and necrcpsied immediately.
2. Each animal will be examined daily for clinical signs of
toxicity.
3. Signs of toxicity noted at other times will be recorded en
room schedules and transferred to the observation sheet if they
persist.
4. Animal Weights - Individual anvnal weights fcr test and cor.trol
groups will be recorded at initiation (day 1) and weekly
thereafter.
-------
Experiment Number 5221.07
5. individual feed consuaiptions will be derived by calculating
the difference in weight of each feed jar plus contents at
the begirjning and. end of the feeding interval and dividing by
the number of days involved.
D. C^thaljtiosccpy
Fundusccpic (indirect c|7thaliocsccpy) and biomicrcsccpic (slitlaito)
examinaticns will be performed pretreatment and at termination en
all animals designated to be terminated at 13-weete.
E. Clinical Pathology
1. The following hematology (all animals fasted overnight) will
be performed on the 20 animals designated for baseline values
(day 1) , on 10 males and 10 females/group designated to be
sacrificed at 45 days and on 10 males and 10 fenales/graup
designated to be sacrificed at termination of the study;
Hemoglobin
Hsnatccrit
Erythrccyte count
Total and differential leukocyte count
Flatlet count
Seticulccyte count
2. The following' clinical chemistry will be determined on serum
samples per the hematolcgy schedule:
Sediura
Chloride
Potassium
Calcium
Fncsphcros
Bleed creatinine
C02
SCOT
Glucose
BUN
Direct and total bilirubin
SAP
Total cholesterol
Albumin
Globulin
Total protein.
p^ /\
o 0
-------
Exoeriment Number 5221,07
3. Urinalysis will be determined on day 45 and at termination as
outlined for heuatology. The following parameters will be
ineasured:
Sr>ecific gravity
pH
Protein • -
Glucose
Kstones • •
Bilirubin
Urobilincgen
Microscopic examination
?. Necropsy and Histcpathlcgy:
1. A complete, detailed necropsy will be performed on all animals.
2. Animals that die or are sacrificed prior to the scheduled
••j£' sacrifice will be necropsied as soon as possible after death.
"'•••• Animals that can not 'be necropsied iinmfidiately will be stored
in a. refrigerator until necropsy but no longer than 24 hours.
3, From all am'ma is en study, except those designate:1, for baseline
clinical chemistry the following tissues will be collected
and preserved in buffered formalin.
All gross lesions Corpus and cervix uteri
Brain (3 levels) Spleen
Eye Bone (with raarrcw)
Pituitary • Skeletal muscle
Salivary gland ' Lynch node
Heart Spinal cord
Thymes ' Mammary gland
Thyroid (with parathyroid) Aorta
Lungs (with mainsten bronchi) Sciatic nerve
Trachea
Esophagus
Stercach
Small and large intestine
Adrenals
Pancreas
Liver
Kidneys
Urinary bladder
"", Testes
Prostate
Ovaries r- 1
i> 1
-------
Exceriment Number 5221,07
Histcpathological evaluation will be performed on all abnormal
tissues and lesions of all animals on study. All listed
tissues will be saved from all rats at the 45-day sacrifice
for possible future evaluation. All the above listed tissues
will be evaluated on all animals sacrificed because of a irarifaurd
condition, thcsa that die • on test, and all control and high-
dose ap-i.Tr.aTs sacrificed at the 13 week termination.
Histqpathology in the • mid and lew cose groups will only be
required for gross lesions and apparent target organs. Target
organs will be determined from previous studies, clinical
data, and the histcpatholcgy in the high-dose level group.
All lesions will be rated according to their severity.
5. At t-PT-pjjai sacrifice, in addition to terminal body weight,
the heart, liver, spleen, brain, kidneys (irdividually) ,
gonads (individually) , adrenals and thyroid/parathyroid will_
be weighed to three significant figures. Organ weight to
body weight ratios will be computad.
G. Statistical Procedures:
In general, the data will be ex?jnined using analysis of variance
techniques followed by a multiple conparison procedure for detecting
differences between pairs of means. Scraa anatomical and clinical
pathology data may require ncncarametric techniques to aid in
interpretation .
H. Data Collections and Reporting:
Abnormal observations, body weights, feed consumptions, dose
formulation documentation, and general study conrsents will be
recorded in laboratory notebooks. Clinical laboratory data
will be recorded in notebooks or will be direct instrument or
ccraputsr output. Pathology data, including organ weights, will
be recorded en individual loose-leaf pathology sheets (one per
* animal) . At the completion of the study, all data and specimens
will be transferred to the Quality Assurance Unit for storage in
the test laboratory archives.
The following data will be collected and included in the final report:
o Sections en introduction, materials and methods, conclusions and
discussion
o Results of all chemical analyses
o Abnormal appearance or behavior
o Individual and mean body weights initially and weekly through
13 weeks
p Results of the cphthalioolcgical examination _ r_
-------
Experiment Number 5221.07
o Individual and mean hematology, bleed chemistry and urinalysis
as outlined.
o Individual and mean organ weights (heart, liver, spleen, brain,
kidneys, gonads, adrenals, and thyroid/para.thyroid) from all
animals at termination
o Individual necropsy observations of all animals
o Individual histcpathology of tissues as outlined.
XI. PEOORDS TO EE MAINTAINED
All raw data pertaining to the conduct of this study including the
final report will be retained as the regulations require in the archives
at Microbiological Associates Inc., 5221 River Read, Eethesda, MD
20816. If at sane time in the future any of these data are to be
discarded, the sponsor will be first notified to obtain perimissicn.
XII. STANDARD OPERATION PROCEDURES AND P5CrrCOOL ALTERATION
All procedures not specified in this protocol will be performed in
accordance with the Microbiological Associates Inc. Standard Operating
Procedures' Manual and in compliance with the FDA's 'Gccd Laboratory
Practice Regulations.
Alterations of the study may be made after the study has been
initiated. In the event that the sponsor verbally authorizes a
change in protocol, such change will be honored by Microbiological
Associates Inc. However, it is then the responsibility of the
sponsor to produce written verification of the verbal authorization,
which will result in the issuance of an official protcccl amendment.
XIII. R£KJN5I3ILJ.'i'LhS
1. L.T, Mulligan, Ph.D: Principal Investigator/Study Director
2f Earry S. Dsvine, D.Sc., D.A.B.T.: lexicologist
3. Locas H. Brennecke, V.M.D., Fh..D.: Veterinary Pathologist
4. John Miller, DVM, AdAM: laboratory Animal Veterinarian
5. Harold J. Paulin, M.S., Qiemist
6. Jean L. Causer, B.S.: Operations Supervisor
7. Nona S. Karten, M.A.: Quality Assurance
-------
Experiment Nui±er 5221.07
XIV.
1. Contract with Research Triangle Institute.
L.T. Mulligan] Ph.D. /
Principal Investigator
Sponsor
'•:
Date'
Date
-------
ORIGINAL
PROTOCOL AMENDMENT
Data: September 24, 1985
Study No.: 5221.07
Title: Subchronic Toxicity of Meta-Cresol in Sprague Dawley Rats
Amendment:
1. Page 1, Part HI, Section A: Scheduled Initiation Date: 3 October 1985.
Section B: Scheduled Termination Date: 2 January 198^
Reason: Insufficient number of animals available from original shipment.
2. Page 3, Part IV, Section C, No. 2c: Change "Micoklene" to "Mikroklene.11
Reason; Misspelled in protocol.
3. Page 5, Part IX, Section A: Randomization: 130 and not 120 armnals will
be randomized.
Reason: Incorrect in protocol.
4. Page 7, Part X, Section C, No. 2: Clinical Observations: Change "examined
daily" to "examined weekly."
Reason; Incorrect in protocol.
Date
Sponsor . Date
fj P-'
5 5
-------
Experiment Number 5221.07
Received by RA/QA
SUBCHRQNIC TOXICTTY OF META-CRE50L IN
gPRAGUE DAWIEY RATS
I. PURPOSE
The purpose of this study is to determine the toxic effects of
m-cresol when administered by gavage for 13 weeks to Sprague Dawley
rats.
II. SPONSOR AND TESTING FACILITY
A. Sponsor Name: Research Triangle Institute (RTI)
B. Sponsor Authorization Date: (See last page)
C. Protocol Approval Date: (See last page)
D. Testing Facility: Microbiological Associates Inc.,
5221 River Road
Bethesda, Maryland 20816
E. Principal Investigator (Study Director); Louis T. Mulligan, Ph.D.
F, Toxicologist: Barry S. Levine, D.Sc., D.A.B.T.
III. TEST SCHEDULE
A. Scheduled Initiation Date; 3 October 1985
B. Proposed Termination Datet 2 January 1985
THIS PAGE REVISED-
Study No. gll/. j")
•=ZL __ 9/3 L-/
-------
Experiment Number 5221.07
2. Spills and Leakage
Persons not wearing the appropriate protective
equipment and clothing should be restricted from
areas of spills or leaks until cleanup has been
coopleted.
If m-cresol or solutions of it are spilled the following
steps should be taken:
a. Ventilate area of spill. Eliminate all heat
and ignition sources.
b. Use vermiculite, sodium bicarbonate, sand, or
paper towels to absorb the oil.
c. Wash area with detergent and water or Mikroklene and
water. Mnse well with water.
d. Dispose of all material in the cleanup as
hazardous waste.
3. Waste and_ Disposal Procedures
Securely package and label, in double bags, all
solid waste material and dispose of by
incineration or by burial at a secured landfill.
Dispose of liquid waste in liquid hazardous waste
drums.
4. Preparation of Doses
Doses will be prepared in the Carcinogen Handling-
Room, 3rd floor, 5221 River Road, Bethesda, MD. 20816.
THIS PAGE REVISED
Sfucfy No.
Signature
-------
Experiment Number 5221.07
F. Cage Change Schedule: Cages will be changed every other week.
G. Feeder Change Schedule: Once weekly.
H. Rack Changes: Every other week.
I. Air Change: At least 12-15 per hour.
J. Bedding Changes: Twice weekly.
K. It is not expected that there are contaminants in the feed or
water which would have any influence on the study.
VIII. QUARANTINE
A. Animals will be maintained in quarantine for 12-16 days. The
cleaning, feeding and watering procedures will be the same as
described above for the test period. Animals will be group
housed during the quarantine period, but individually housed at
test animal selection.
B. Animals will be observed twice daily for signs of illness or
death and all unusual observations will be reported to the Principal
Investigator or Director of Veterinary Medicine.
C. Animals will be examined during quarantine and approved for use
by the Director of Veterinary Medicine prior to being placed on
test. Health Status Evaluation form RA/QA 11 will be completed
by the Study Director and Director of Veterinary Medicine.
IX. RANDOMIZATION. ANIMAL NUMBERING, STATISTICAL ANALYSIS
A. Randomization: Daring the quarantine period, the animals will be
randomized as follows: Starting with one sex of the species to be
randomized, each animal will be weighed, placed into individually
numbered cages and separated into one of a number of weight range
groups which are based on successive intervals of 5 grams. The
weight of each is recorded on paper. After all animals have been
placed into their appropriate weight range groups, 130 of the animals
with weights closest to the median weight will be randomized.
Outliers will be used for health check evaluation and baseline
evaluations or killed.
After the appropriate number of animals per sex have been selected,
a random number table will be computer generated for each sex
and used to allocate animals to a treatment group.
THIS PAGE REVISED
.Study No.
Signature • Dal*
-------
• ic. -,
""••'.*•'
Experiment Number 5221.07
B. Treatment Groups
Animals will be randomly assigned to groups with the following
design:
Number of Animals
Dose Level
Treatanent (mcr/kg/day) Male Female
1
2
3
4
Negative control
m-cresol
m—cresol
m-cresol
Baseline clinical
pathology
50
150
450
30
30
30
30
30
30
30
30
10
10
The ten male and ten female animals in group #5 will be sacrificed
at study initiation for collection of baseline data on hematology
and serum chemistry.
Ten male and ten female animals (selected prior to initation of
the study) from each remaining group will be sacrificed at 45-days
post-treatment initiation for clinical pathology and collection
of tissues for possbile later evaluation. The following organs
will be weighed: heart, liver, spleen, brain, kidneys (individually),
gonads (individually), adrenals and thyroid/parathyroid.
C. Clinical Observations
1. Animals will be observed twice daily (once in the morning and
once in afternoon) seven days per week for moribundity/mortality.
Moribund animals unlikely to survive until the next observation
will be sacrificed and necropsied immediately.
2. Each animal will be examined weekly for clinical signs of
toxicity.
3. Signs of toxicity noted at other times will be recorded on
room schedules and transferred to the observation sheet if they
persist.
4. Animal Weights - Individual animal weights for test and control
groups will be recorded at initiation (day 1) and weekly
thereafter.
THIS PAGE REVISED
-------
ORIGINAL
PROTOCOL AMENDMENT
Date: October 16, 1985
Study No.: 5221.07
Title: Subchronic Toxicity of Meta-Cresol in Sprague Dawley Rats
Amerdment:
5. Page 7, Part X, Section B: Treatment Groups: Delete the following sentence.
"The following organs will be weighed: heart, liver, spleen, brain,
kidneys (individually), gonads (individually), adrenals and thyroid/
parathyroid.
Reason: Per discussion with the Sponsor, organ weights are not necessary
at the 45-day interim kill.
6. Page 8, Part X, Section E, No. 1: Add prothrcmbin time (PT) and activated
partial thrornboplastin time (APTT), and delete platelet count.
Reason: PT and APTT are better estimates of clotting potential than
platelet count.
^—^
(^^-Z^lx^^L^ e^
Study Directo^ 7 Date
Sponsor Date
GO
-------
Experiment Number 5221.07
B. Treatment Groups
Animals will be randomly assigned to groups with the following
design:
Number of Animals
Dose Level
Group Treatment fmg/kg/dayl Male Female
1 Negative control
2 m-cresol 50
3 m-cresol 150
30
30
30
30
30
30
m-cresol
Baseline clinical
pathology
450
30
10
30
10
The ten male and ten female animals in group #5 will be sacrificed
at study initiation for collection of baseline data on hematology
and serum chemistry.
Ten male and ten female animals (selected prior to irritation of
the study) from each remaining group will be sacrificed at 4 5-days
post-treatment initiation for clinical pathology and collection
of tissues for possbile later evaluation.
C. Clinical Observations
1. Animals will be observed twice daily (once in the morning and
once in afternoon) seven days per week for moribundity/mortality.
Moribund animals unlikely to survive until the next observation
will be sacrificed and necropsied immediately.
2. Each animal will be examined weekly for clinical signs of
toxicity.
3. Signs of toxicity noted at other times will be recorded on
room schedules and transferred to the observation sheet if they
persist.
4. Animal Weights - Individual animal, weights for test and control
groups will be recorded at initiation (day 1) and weekly
thereafter.
61
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4HIS PAGE REVISED
Signature Dale
Experiment Number 5221.07
5. Individual feed consumptions will be derived by calculating
the difference in weight of each feed jar plus contents at
the beginning and end of the feeding interval and dividing by
the number of days involved.
D. OphthalJnoscopy
Funduscopic (indirect opthalmoscopy) and biomicroscopic (slitlamp)
examinations will be performed pretreatment and at termination on
all animals designated to be terminated at 13 -weeks.
E. Clinical Pathology
1. The following hematology (all animals fasted overnight) will
be performed on the 20 animals designated for baseline values
(day 1) , on 10 males and 10 females/group designated to be
sacrificed at 45 days and on 10 males and 10 females/group
designated to be sacrificed at termination of the study:
Hemoglobin
Hematccrit
Erythrocyte count
Total and differential leukocyte count
Prothrombin time (FT)
Activated partial thromboplastin time (APIT)
Reticulocyte count •
2. The following clinical chemistry will be determined on serum
samples per the hematology schedule:
Sodium
Chloride
Potassium
Calcium
Phosphorus
Blood creatinine
SGPT
SCOT
Glucose
BUN
Direct and total bilirubin
SAP
Total cholesterol
Albumin
Globulin
Total protein
3
-------
ORIGINAL
PROTOCOL TENEMENT
Date: November 26, 1985
Study No.: 5221.07
Title: Subchronic Toxicity of Meta-Cresol in Sprague Dawley Rats
Amendment:
4
7. Page ^, Part VII, Section E, Feed: Substitute "Purina standard lab chow"
with "Purina Rodent Chow No. 5001."
Reason: Omitted in protocol.
8. Page 5, Part VII: Add the following: Section L. Room Number: Room #369
Reason: Not included in protocol.
9. Page 5, Part VIII, Quarantine, Section B: Unusual observations
during the quarantine period can also be reported to the Study Toxicologist."
Reason: Omitted in protocol.
10. Page 9, Part X, Section F, No.2: If necessary, animals which die on
test are stored in a refrigerator until necropsy but no longer than 16 hours.
Reason: Incorrectly stated as 24 hours in protocol.
Study Director * Date ^ [ r
Sponsor Date
63
-------
THIS PAGE REVISED
Study No. 5*331.0*1
Signature
Dale
Experiment Number 5221.07
V.
VII.
5. Analysis of Solutions
The stability of the test solution will be determined
after storage for the same period and under the same
condition to be used in the study.
The -accuracy of formulation will be checked by analysis
of samples taken from solutions prepared for
administration during weeks 1, 2, 4, 8 and 13 of
treatment.
TEST SYSTEMS
A. Animals
1. Strain/Species: Sprague Dawley Eats
2. Number/Sex: 130 males/130 females
Age: 5-6 weeks old at start of dosing
3.
4.
Supplier: Charles River Breeding Laboratories
Lakeview, NY
Justification of Test Animal: The test animal (Sprague
Dawley Rats) was specified by the sponsor and is a routine
laboratory animal utilized in ^maii rodent subchronic
toxicology studies.
VI. HOUSING
The animals will be individually housed in polycarbonate shoe boxes
marked with a test article code and held on stainless steel racks
equipped with an automatic watering system. Heat treated hardwood
chips will be used for cage bedding. Racks will be periodically
repositioned within the room to minimize any effect of variation in
light intensity , temperature, etc.
ANTMAL
A. Temperature: 72° ± 3°F
B. Humidity: 50 ± 15%
C. Light Cycle: 12 hour cycle
D. Water: Washington Suburban Sanitary Commission Potomac
Plant; untreated; ad libitum.
64
MICROBIOLOGICAL
-------
THIS PAGE R£Vli:D
• £:ijvfy No,
Experiment Number 5221.07
E. Feed: Purina Bodent Chow No. 5001.
F. Cage Change Schedule: Cages will be changed every other week.
G. Feeder Change Schedule: Once weekly.
H. Pack changes: Every other week.
I. Air Change: -At least 12-15 per hour.
J. Bedding Changes: Twice weekly.
K. It is not expected that there are contaminants in the feed or
water which would have any influence on the study.
L. Boom Number: Boom $369.
VIII. QUARANTINE
A. Animals will be maintained in quarantine for 12-16 days. The
cleaning, feeding and watering prccedures will be the same as
described above for the test period. Animals will be group
housed during the quarantine period, but individually housed at
test animal selection.
B. Animals will be observed twice daily for signs of illness or
death and all -unusual observations will, be reported to the Principal
Investigator, Study Toxicologist or Director of Veterinary Medicine.
C. Animals will be examined during quarantine and approved for use
by the Director of Veterinary Medicine prior to being placed on
test. Health Status Evaluation form EA/QA 11 will be completed
by the Study Director and Director of Veterinary Medicine.
IX. I&NDCMI2ATION, ANIMAL NUMBERING, STATISTICAL ANALYSIS
A. Randomization: During the quarantine period, the animals will be
randomized as follows: Starting with one sex of the species to be
randomized, each anional will be weighed, placed into individually
numbered cages and separated into one of a number of weight range
groups which are based en successive intervals of 5 grams. The
weight of each is recorded on paper. After all animals have been
placed into their appropriate weight range groups, 130 of the animals
with weights closest to the median weight will be randomized.
Outliers will be used for health check evaluation and baseline
evaluations or killed.
-------
Experiment timber 5221.07
3. Urinalysis will be determined on day 45 and at termination as
outlined for hematology. The following parameters will be
measured:
Specific gravity
pH
Protein
Glucose
Ketones
Bilirubin
Urobilinogen
Microscopic examination
F. Necropsy and Histcpathlcgy:
1. A complete, detailed necropsy will be performed on all animals.
2. Animals that die or are sacrificed prior to the scheduled
sacrifice will be necropsied as soon as possible after death.
Aninals that can not be necropsied immediately will be stored
in a refrigerator until necropsy but no longer than 16 hours.
3. From all animals on study, except those designated for baseline
clinical chemistry the following tissues will be collected
and preserved in buffered formalin.
All gross lesions . Corpus and cervix uteri
Brain (3 levels) Spleen
Eye Bone (with marrow)
Pituitary Skeletal muscle
Salivary gland Lymph node
Heart Spinal cord
Thymus Mammary gland
Thyroid (with parathyroid) Aorta
lungs (with mainstem bronchi) Sciatic nerve
Trachea
Esophagus
Stomach
Small and large intestine
Adrenals
Pancreas
Liver
Kidneys
Urinary bladder
Testes
Prostate
Ovaries
-------
PROTOCOL AMENEMENT
Date: August 21, 1986
Study No.: 5221.07
Title: Subchronic Toxicity of Meta-Cresol in Sprague Dawley Rats
Amendment:
11. The interim sacrifice was conducted ever a two-day period (test days 46
and 47), and the terminal sacrifice was conducted over a three-day
period (test days 92, 93 and 94).
Reason; The large number of aninals in the study did not allow
necropsies and clinical pathology evaluations to be conducted in one day
at either the interim or terminal sacrifice.
12. Page 6, Part X, Section A, No. 3:
"for a total period of 13 weeks" should read "for a period of thirteen
weeks or until sacrifice.
Reason; Required due to staggered sacrifice schedule.
13. Page 8, Part X, Section D:
Delete "and biomicroscopic (slitlamp)11.
Reason: Incorrect in protocol; it was never intended to be done by the
ophthalmologist.
study Diiector/ / Date
Sponsor Approval Date 6 7
2& MICROBIOLOGICAL
-------
PROIOODL AMENCMENT
Data: August 27, 1986
Study No.: 5221.07
Title: Subchronic Toxicity of Meta-Cresol in Sprague Dawley Rats
Amendment:
14. Page 4, Part VII, Section E, Feed: Delete entire section.
Reason: Section E was listed twice, on bottom of page 4 and at the top
of page 5. The listing on page 5 included a better description of the
feed.
Study (Director / /Date
Sponsor Approval N-~—/ Date
'/
68
MICROBIOLOGICAL
-------
PROTOCOL AMENEMENT
Date: September 5, 1986
Study No.: 5221.07
Title: Subchronic Toxicity of Meta-Cresol in Sprague Dawley Rats
Amendment:
15. Alterations in the measurements of the following clinical pathology
parameters occurred as follows.
Calcium was not measured at
pretest or at the interim
sacrifice.
Urinary hemoglobin was
evaluated.
Reason
Technical error,
The "dipsticks" use for
urinalyses contained hemoglobin.
The results were included in the
final report.
Study(Director
Sponsor Approval
^5
"
Date
69
MICROBIOLOGICAL
-------
QUALITY ASSURANCE STATEMENT
Study Title: SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE
DAWLEY RATS
Study Number: 5221.07
Study Director: L. Thomas Mulligan, Ph.D.
Initiation Date: October 3, 1985
Review Completed Date: September 23, 1986
This study has been divided into a series of phases. Using a
random sampling approach, Quality Assurance monitors each of
these phases over a series of studies. Procedures, documenta-
tion, equipment, etc., are examined in order to assure that the
study is performed in accordance with the U.S. FDA Good
Laboratory Practice regulations (21CFR58), the U.S. EPA GLPs
(40CFR792 and 40CFR160), and the OECD guidelines and to assure
that the study is conducted according to the protocol.
The following are the inspection dates, phases inspected, and
report dates of QA inspections of this study.
-------
DATES/PHASES
IPECT ON 85/09/20 - 85/09/20,TO STUDY DIR 85/09/20,TO MGMT 85/09/20
PHASES: PROTOCOL REVIEW
INSPECT ON 85/12/26 - 85/12/26,TO STUDY DIR 85/12/26,TO MGMT 85/12/30
PHASES: DOSE PREPARATION
INSPECT ON 86/04/10 - 86/04/14,TO STUDY DIR 86/04/14,TO MGMT 86/09/23
PHASES: DATA REVIEW
INSPECT ON 86/05/13 - 86/05/13,TO STUDY DIR 86/05/13,TO MGMT 86/05/13
PHASES: PATHOLOGY NARRATIVE REVIEW
INSPECT ON 86/08/28 - 86/09/02,TO STUDY DIR 86/09/02,TO MGMT 86/09/23
PHASES: FINAL REPORT
This report describes the- methods and procedures used in the
study and the reported results accurately reflect the raw data
of the study.
7 I *• 3 1 9 fc
Qu/lity Assurance/ Date
RA/QA Department
71
-------
Final Report
Study No. 5221.07
APPENDIX A
1WO-WEEK K^CT-FINDING/EXPLDRATORY STUDY OF MEIA-CSESOL
IN SERAGUE OAKLEY RATS
7
A-l
-------
Study No. 5221.07
-vl
CO
Test
Day
DAY 1
DAY fl
DAY 15
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF META-CRESOL IN SPRAGUE OAWLEY RATS
HALE BODY WEIGHT DATA (g)
0 mg/kg/day S mg/kg/day 10 ng/kg/day 25 mg/kg/doy 50 mg/kg/day
153.0 t 8.2( 10) 157.4 t 10.4( 10) 161.7 i 11.2< 10) 154.1 t 13.3( 10) 157.1 ± 12.1( 10)
207.2 t 10.0( 10) 213.4 t 11.2( 10) 222.7 t 16.3( 10) 210.7 t 20.9( 10) 216.7 t 17.0( 10}
255.0 t 15.4{ 10) 258.9 * 15.5C 10) 272.0 ± 28.6{ 10) 255.8 t 23.3( 10) 266.1 t 21.3( 10)
100 mg/kg/day
158.7 ± 13.6( 10)
211.3 i 23.Q( 10)
256.7 t 23.9( 10)
Results presented as mean ± standard deviation C K
-------
Study Ho. 5221.07
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF HETA-CRESOL IN SPRAGUE DAVILEY RATS
FEHALE BODY WEIGHT DATA
-------
Study Ha. 5221,07
TWO UEEK RAMGE-FINOING/EXPtORATORY STUDY OF META-CRESOL !H SPRAGUE DAWIEV RATS
HALE FOOD CONSUMPTION DATA (g/diy)
Test
Ueek Q rog/kg/day 5 mg/kg/day 10 mg/kg/day 25 mg/kg/day 50 mg/kg/day 100 mg/kg/day
UEEK 1 19.9 l 1.0{ 10) 20.7 t 1.K 10) 20.1 ± 4.7{ 10) 21.5 t 3.1( 10) 21.0 ± 1.7( 10) 19.1 ± 3.0( 10)
UE« 2 25.3 t 6.9( 10) 25.3 ± 2.9C 10) 23.0 t 8.7( 10) 22.9 t 2.7< 10) 23.7 ± 1.7( 10) 23.4 t 2.8( 10)
Results presented as mean i standard deviation ( H )
-------
Study No. 5221.07
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF HETA-CRESOL !H SPRAGUE DAWLEY RATS
FEMALE FOOD COMSUHPT10H DATA (g/day)
Test
Week 0 mg/kg/day 5 rag/kg/day 10 mg/kg/day 25 mg/kg/day 50 mg/kg/day 100 mg/kg/doy
UEEK 1 15.1* 4.9(10) 17,01 5,1(10) 18,1 + 1.0(9)16-7± 3.6(10) 19.8 f 4.5(10) 18.2 t 1.7(10)
WEEK 2 18.2 * 1.1( 10) 19.9 t 4.5( 10) 17.5 t 3.0( 10) 12.0 t fl.3( 10)* 15.1 t 5.1C 10) 13.5 t 5.8( 10)
Statistically significant difference from control group
using ANOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean ± standard deviation ( H )
-------
Study Mo. 5221.07
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF META-CRESOL IN SPRAGUE OAWLEY RATS
HALE BODY WEIGHT DATA (9)
ANiMAL NUMBER DAY 1 DAY 8 DAY 15
DOSE LEVEL
0 mg/kg/cfay
mg/kg/day
10 mg/kg/day
25 mg/kg/day
2281
2282
2283
2234
2285
2286
2287
2238
2239
2290
2291
2292
2293
2294
2295
2296
2297
• 2298
2299
2300
2301
2302
2303
2304
2305
2306
2307
2308
2309
2310
2311
2312
2313
2314
2315
2316
2317
2318
2319
2320
152.4
163.6
160.8
152.3
156.9
142.3
149.6
154.5
137.5
159.9
166.8
172.6
157.0
155.6
152.6
157.6
153.5
156.2
134.7
167.3
145.5
150.9
171.8 .
165.2
144.3
177.1
162.7
162.4
167.7
169.9
152.7
135.9
162.0
166.7
142.9
162.7
176.0
135.5
152.3
154.2
210.7
217.9
214.5
207.3
215.8
194.0
208.1
203.4
186.6
213.4
225.0
229.3
211.6
209.9
207.5
224.4
207.1
211.7
190.6
216.7
200,2
210.8
235.7
221.6
194.6
233.6
231.9
219.2
239.3
235.5
205.5
183.3
221.1
229.9
188.4
221.8
243.9
182.0
221.9
209.6
267.1
269.8
274.6
256.8
266.5
253.2
236.9
242.7
227.4
254.6
277.4
276.3
260.6
252.9
236.8
280.8
253. 3
258.9
237.5
254.2
254.1
226.9
288.8
264.2
226.3
299.6
293.4
271.5
296.4
299.2
248.0
230.0
259.8
279.8
239.8
266.5
299.3
221.3
263.5
249.9
A-6
-------
Study Ms. 5221.07
TWO WEEK RANGE-FIND INC/EXPLORATORY STUDY Of META-CRESCL IN SPRACUE OAWLEY RATS
MALI BODY WEIGHT DATA (g)
ANIHAl NUMSES DAY 1 DAY 8 DAY 15
DOSE LEVEL
50 mg/kg/day
100 mg/kg/day
2321
2322
2323
2324
2325
2326
2327
2328
2329
2330^
2331
2332
2333
2334
2335
2336
233?
2338
2339
2343
158.4
146.3
164.4
145.0
166.6
136.6
159.8
159.0
17S.9
155.9
158.4
161.4
160.3
154.9
158.2
179.9
146.4
135.6
180.0
152.0
215.9
203.0
224.4
198.1
230.2
195.5
219.3
2Z0.2
252.4
208.1
211.0
209,5
208.0
193.8
205.6
248.9
205.9
194.7
254.0
181.8
272.9
253.6
280.4
236.4
269.7
248.9
285.5
261.5
306.9
245.6
261.3
265.3
238.4
246.3
246.4
303.5
247.1
244.3
289.3
225.3
78
A-7
-------
Study No. 5221.07
TWO UESK SANGE-FIN01NG/EXPLORATORT STUDY OF HETA-CRESQl IN SPRAGUE DAULEY RATS
FEMALE 800Y WEIGHT DATA (g)
ANIHAL NUMBER DAY 1 DAY 8 DAY 15
0 mg/kg/day 2341
2342
2343
2344
2345
2346
2347
2348
2349
2350
5 mi/kg/day 2551
2352
2353
2354
2355
2356
2357
2358
2359
2360
10 tni/kg/day 2361
2362
2363
2364
2365
2366
2367
2368
2369
237Q
25 mg/icg/day 2371
2372
2373
2374
2375
2376
2377
2378
2379
23EO
144.3
118.0
116.8
129.2
113.5
130.9
130.4
111.6
122.6
119.0
127.8
120.7
133.1
124.8
119.5
118.8
122.1
136.5
122.1
13S.4
113.8
117.0
115.8
128. 4
124.1
119.0
131.1
118.0
123.8
117.4
112.4
121.2
115.4
125.0
124.5
120.3
121.7
115.0
125.4
118.8
166.3
161.4
123.4
181.3
102.8*
175.5
171.0
159.5
164.1
125.0
175.2
158. S
185.8
170.1
91.7*
172,4
155.6
18S.5
164.5
114.6*
154.0
159.2
166.1
169.2
159.8
165.7
169.8
154.0
164.7
106 .2*
166.9
155.7
151.5
160.1
100.8*
173.8
164.6
156.0
165.4
172.0
202.0
189.9
143.8
199.2
152.8
185.2
201.6
189.6
187.1
158.4
203.7
187.5
213.2
2QE.2
106.3
189.2
177.6
215.0
183.6
166.0
186.6
175.6
190.3
193.2
142.3
195.3
180.4
172.5
184.8
116.6
198,5
171.9
173.9
190.7
104.9
184.0
191.4
174.6
192.3
192.5
* Signs of dehydration noted.
A-8
-------
Study No. 5221.07
TWO WEEK RANGE-F1N01NG/IXPLQRATORY STUDY OF META-CRESOL !H SP8AGUE DAULEY RATS
FEMALE BODY UEIGHT DATA (g)
AH IHAL NUMBER DAY 1 DAY 8 CAY 15
DOSE LEVEL
50 mg/kg/day
100 mg/kg/day
2381
2382
2383
2384
2385
2386
2387
2188
2389
2390
2391
2392
2393
2394
2395
2396
2397
2398
2399
2400
129.2
121.2
116.5
129.9
116.2
113.1
137.7
136.5
125.9
119.6
118.8
134.6
137.7
131.0
122.5
131.6
130.5
135.3
141.0
11'.. 2-
177.2
167.3
164.3
170.0
146.4
161.0
172.6
176.6
182.7
180.3
151.7
172.7
171.3
162.7
172.0
135.4
161.5
175.6
179.0
147.8
201.5
191.8
177.5
197.2
159.0
171.0
196.3
207.8
198.7
207.3
175,9
195.8
193.8
193.4
207.0
209.9
185.0
199.7
197,3
165.2
80
A-9
-------
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY Cf MEU-C8ESOL
HALE FOOD CCHSUMPTICH DATA
-------
Study No. 5221,07
TWO WEEK RANCE-FIKDING/EXPLORATORr STUOlf OF HETA-CRESQL IN SPRAGUE DAWLEY RATS
KALE FOOD CONSUMPTION DATA (9)
[Feeder Weights]
ANIMAL NUMBER new feeder 1 old feeder 1 new feeder 2 old feeder 2
DOSE LEVEL
50 mg/lcg/day
100 nsg/kg/day
2321
2322
2323
2324
2325
2326
2327
2323
2329
2330
2331
2332
2333
2334
2335
2336
2337
2338
2339
2340
635.4
630.8
548.1
632.8
665.1
604.4
687.9
621.8
645.3
610. 4
561.5
626.6
554.4
559.6
656.3
656.9
551.2
633.7
702,6
704.7
490.6
491.4
399.1
506.5
504.1
467.4
538.1
469.4
479.6
463.3
427.3
506.8
420.6
440.1
528.1
496.0
412.6
503.6
529.3
604.7
535.4
546.0
545.6
533.4
539.9
531.1
538.1
- 533.1
519.3
532.7
531.5
533.9
529.1
530.7
528.1
530.1
533.2
532.4
529.3
604.7
369,9 '
380.0
378.3
391.0
383.0
372.9
349.0
365.8
345.0
362.0
371. S
367.9
384.4
359.6
386.3
344.9
365.8
374.9
326.3
462.4
82
A-11
-------
Study No. 5221.07
TUO WEEK 8ANGE-F1NDING/EXPLOSATQRY STUDY OF MSTA-CRESOl IN SPRAGUE DAHLEY RATS
HALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NUMBER WEEK 1 WEEK 2
DOSE LEVEL
0 mg/kg/day
5 rog/kg/day
10 mg/kg/day
25 mg/kg/day
2281
2282
2283
2284
2285
2286
2287
2288
2289
2290
2291
2292
2293
2294
2295
2296
2297
2298
2299
2300
2301
2302
2303
2304
2305
2306
2307
2308
2309
2310
2311
2312
2313
2314
2315
2316
2317
2318
2319
2320
20.3
19.0
20.4
19.1
21.1
18.2
20.5
21.0
18.8
20.6
19.7
21.1
21.1
21.6
21.1
23.0
19.4
19.9
19.3
20.7
20,3
20. 2
22.7
7.1
19.8
22.1
23.5
21,5
21,3
22.9
21.8
17.1
20.4
23.1
18.7
21.1
22.5
1S.B
23.7
28.2
23.2
21.9
24.3
20.9
25.3
39.7
19.1
23.6
19.3
35.8
26.7
26.9
28. a
23.3
25.1
30.4
25.0
23.5
21.0
22.5
24.3
24,3
21.5
26.2
27.6
15.5
16.2
22.8
9.3
41.7
23.7
19.1
22.1
25.5
22.0
28.3
20.6
22.2
23.2
21.9
83
A-12
-------
Study Mo. 5221.07
TUG WEEK RANGE-FINDING/EXPLORATORY STUD? OF META-CRESQL IN SPRACUE DAWLEY RATS
MALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NUMiER WEEK 1 WEEK 2
DOSE UEVEt
50 rag/kg/day
100 mg/kg/day
2321
2322
2323
2324
2325
2326
2327
2328
2329
2330
2331
2332
2333
2334
2335
2336
2337
2338
2339
2340
20.3
19.9
21.3
18.0
23.0
19.6
21.4
21.8
23.7
21.0
19.1
17.1
19.1
17.1
18.4
23.0
19.8
18.6
24. S
U.3
23.6
23.7
23.9
20.3
22.4
22.6
27.0
23.9
24.9
24.4
22.8
23.7
Z0.7
24.4
20.3
26.5
23.9
22.5
29.0
20.3
84
A-13
-------
Study No. 5221,07
TWO WEEK RANGE-FIN01NG/EXP10RATQRY STUDY OF META-CRESCl SN SPRAGUE DAWIEY RATS
FEHALS FOOD CONSUMPTION DATA (g>
[Feeder Weights]
ANIMAL NUMBER new feeder 1 old feeder 1 new feeder 2 old feeder 2
DOSE liVEL
0 ing/kg/day
5 mg/kg/day
10 mg/Scg/day
25 mg/kf/day
2341
2342
2343
2344
2345
2346
2347
2348
2349
2350
2351
2352
2353
2354
2355
2356
2357
2358
2359
2360
2361
2362
2363
2364
2365
2366
2367
2368
2369
2370
2371
2372
2373
2374
2375
2376
2377
2378
2379
2380
589.3
618.5
591.3
644.4
616.3
530.5
642.9
606.0
638.9
555.7
543.9
586.9
554.8
594.5
593.4
604.8
567.3
507.7
661.0
r 601.0
628.1
628.9
602.3
605.2
600.4
594.5
630.2
624.6
673.9
485.3
566.9
600.4
539.9
682.2
646.6
657.2
692.0
639.5
656.7
5S4.9
449.7
501,1
527.7
505.9
571.8
403.0
516.9
486.8
522.4
490.6
401.4
462.0
410.3
461.3
548.2
466.0
440.5
357.7
53S.8
540.9
492.7
508.2
472.7
479.9
477.1
453.6
503.6
506.4
553.0
535.9
433.3
490.9
418.0
566.6
594.9
520.7
577.8
522.3
528.7
444.3
548.7
566.0
527.6
505.9
571.8
533.3
516,9
562.2
563.4
537.0
558.8
546.7
558.9
541.6
548.2
550.5
540.0
544.5
538.8
540.9
535.4
559.4
541.3
532.2
513.6
513.2
503.6
506.4
553.0
535.9
520.3
583.7
557. 1
566.6
594.9
520.7
571.3
522.3
528.7
538.4
410.1
442.3
397.8
. 377.4
447.2
419.1
386.4
425.8
449.0
411.3
413.9
421.6
417.4
325.0
453.9
413.4
413.4
391.1
406.0
422.7
402.9
453.7
407.1
395,5
396.2
421.2
377.6
383.4
391.9
440.6
513.9
482.5
438.1
437.5 '
509.4
516.6
451.9
411.8
365.8
533.5
A-14
-------
Study No. 5221.07
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY Of META-CRESOL IN SPRAGUE DAULSY RATS
FEMALE FOOD CONSUMPTION DATA
[Feeder Ueights]
ANIMAL NUMBER new feeder 1 old feeder 1 new feeder 2 old feeder 2
DOSE LEVEL
50 rag/ki/day
100 mg/kg/day
2381
2382
2383
2384
2385
2386
2387
2388
2389
2390
2391
2392
2393
2394
2395
2396
2397
2398
2399
2400
668.1
591.4
592.6
622.0
661.6
661.7
653.2
603.4
690.7
653.8
654.0
654.9
669.0
686.8
645.5
674.3
594.4
619.0
608.8
650.5
538.9
435.1
467.8
496.3
540.3
542.9
522.6
465.9
468.1
533.2
550.5
512.5
549,4
561.4
506.8
536.6
477.4
485.3
481.6
523.7
538.9 -
533.7
526.8
547.2
540.3-
442.9
522.6
518.6
526.3
533.2 -
550.5-
512.5-
549.4-
561.4-
506.8-
536.6-
502.8
520.4
529.1
523.7-
442.0
410. S
409.3
420.1
497.9
403.5
392.3
393.4
410.0
393,4
450.3
398.3
437.8
449.9
455.7
408.6
485.3
386.7
479.9
396,1
A-1S
86
-------
Study Ho. 5221.07
TWO WEEK RAHGE-FINDING/EXPLQRATCRY STUDY OF META-CRESQL 1H SPRAGUE DAU'LEY RATS
FEMALE FOOD CONSUMPTION DATA Cg/day)
ANIMAL NUMBER UEEK 1 WEEK 2
DOSE LEVEL
0 mg/kg/day
5 mg/kf/day
10 mg/ kg/day
25 nig/ kg/day
2341
2342
2343
2344
2245
2346
2347
2343
2349
2350
2351
2352
2353
2354
2355
2356
. 2357
2358
2359
2360
2361
2362
2363
2364
Z365
2366
2367
2363
2369
2370
2371
2372
2373
2374
2375
2376
2377
2378
2379
23BO
19.9
16.8
9.1
19. S
6.4
18.2
18.0
17.0
16.6
9.3
20.4
17.8
20.6
19.0
6.5
19.8
18.1
21.4
17.5
8.6
19.3
17.2
IB. 5
17.9'
17,6
20.1
ia.1
16.9
17.3
*
19.1
15.6
17.4
16.5
7.4
19.5
16.3
16.7
18.3
20.1
19.8
17.7
18.5
18.4
17.8
17,0
13.6
19.5
16.3
18.0
20.7
17.9
20.2
30.9
13.5
19.6
18.1
21.9
19.0
16.9
18.9
15.1
19.2
19.5
16,8
13.1
18. Q
17.6
23.0
13.6
0.9
14.5
17.0
13.4
12.2
0.6
17.1
is. a
23.3
0.7
* Invalid weight; excluded from mean
A-16
-------
Study No. 5221.07
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF HE7A-CRESOL IN SPRAGUS DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NUMBER WEEK 1 WEEK 2
OOSf LEVEL
50 mg/kg/day 2381 18.5 13.8
2382 22.3 17.6
2383 17.8 16.8
2384 13.0 18.2
2385 17.3 6.1
2386 17.0 5.6
2337 18.7 18.6
2388 19.6 17.9
2389 31.8 16.6
2390 17,2 20.0
100 ms/kg/day 2391 14.3 14.3
2392 20.3 16.3
2393 17.1 15.9
2394 17.9 15.9
2395 19.8 7.3
2396 19.7 13.3
2397 16.7 2.4
2398 19.1 19.1
2399 18.2 7.0
2400 18.1 18.2
Q Q
o o
A-17
-------
Final Report
Study No. 5221.07
APPENDIX B
MKLXTICKL CHEMISTRY MECHODOIDGY
89
B-l
-------
AMERICAN BIOGENICS CORPORATION
ANALYTICAL REPORT
PROJECT NO.: C/^/) - 3 &
SUBJECT:
i r/ftA/5
S/PL
PAGE
DATE
2S1000G
/ OF /
DEPARTMENT NO. 440
TEST ARTICLE NO.: —
v^£x/
TECHNICIAN
REVIEWED BY
*
DATS \ 2 S
DATE
B-2
Q 0
1 1 \j
-------
ER
^_^
O/1
ENSECO
June 2, 1936
Dr. Dennis D. Diets
Research Triangle Institute
P.O. Box 12194
Research Triangle Park, MC 27709
Dear Dennis:
Zaclosed please find a description of the method ire use for
analysis of compounds by direct aqueous injection as it pertains
;o Tori performed under SPA WA-35.
As you can see, the analysis procedure i3 generally the
same for all compounds differing only in the case of the cresols
which use an alternate coluan and temperature program.
If you have any questions regarding the method or other
specifics, please do not hesitate to contact me.
Sincerely,
'.Y. Henry Camp
Analytical Chemist
VOA Laboratory
:.YHC :a>
2nd.
cc: Dr. Barry Levins (Microbiological Associates)
Dr. Dale Mayhew (American 3iogenics Corp.]
Dr. Crosby Thompkins (Toxicity Research. Laboratories)
B-3 '91
J,- ..••ij.'irii i» oLnC:"U. -J. ' '.i'oiirrfl.n.-. rrjUfi'ji' r-.L- ~uu
-------
This'method covers the determination, of compounds by direct
aqueous injection. The following compounds can be detected
using column A and temperature program A: acetone, methyl
isobutyl ketone (MIBK), isobutyl alcohol, methyl alcohol, ethyl
acetate, n-butyl alcohol and crotonaldehyde. The following
compounds can be detected using system B and temperature
program B: p-, m-, and o-cresol.
2. Summary.
A portion of a, sample is injected directly onto a gas
chromatograph capillary column. The gas chromatograph is
temperature programmed to separate the constituents which are
then detected by a flame ionization detector.
3.
Instrumentation and Apparatus.
3.1. Gas chromatograph -- Hewlett-Packard 5880'with auto-
sampler and integrator. Oven temperature profile A
programmed as hold 8 rain at 50*C,' then to 220°C at
8*C/min and hold 5 min. Program B: hold 5 min at
50*C then to 250'C at 10*C/rain and hold 15 rain.
3.2. Column A — 60 m x 0.32 mm ID, 0.25 vm film SUPEL-
COWAX 10 fused silica capillary column. Set linear
velocity to 25 cm/sec, He, at lOO'C (flow rate = 1.2
ml/min) .
Column B -- 30 m x 0.318 mm ID, 0.25 um film SE - 54
fused silica capillary column. Set linear velocity
B-A
92
-------
to 25 cm/sec, He, at 100*C (flow rate = 1.2
ml/min).
3.3. Injector -- configure for sample splitting and ad-
Just ratio to 100:1. Set heater temperature to
200'C.
3.4. Detector -- Hewlett-Packard flame ionization de-
tector. Hydrogen flow set at 40 ml/min. Air flow
set at 400 ml/rain. Set sensitivity at 2*2 and ad-
Just if necessary. Set heater temperature to
25Q*G.
3.5. Syringes -- 1 ml, 100 pi, and 10 pi gas-tight glass
for diluting and for sample transfer.
4. Reagents.
4.1, Reagent Water -- prepare with. Corning Mega-Pure dis-
tillation system and filter through activated
charcoal prior to use.
4.2. Methylene Chloride -- J. T. Baker "Resi-analysed" or
equivalent.
4.3. Standard Solution -- prepare by adding pure material
to water. Pure material should be assayed reference
liquid such as Chem Serve reagents. If not immedi-
ately available, supplied compound may be used.
4.3.1. Place about 9 nil of solvent into a stoppered 10 ml
flask. Weigh the flask. Add one or two drops of
aure material to the flask and reweigh. Dilute to
B-5
-------
voluae, six well, and store in a teflon-sealed
screw-can vial at 4*C.
5. Calibration.
5.1. External Standard Calibration -- Prepare working
standards to bracket the concentration range, of the
samples'of interest. Working standards are prepared
by diluting the standard solution with water or
aethylene chloride if the samples are corn oil
based.. Analyze according to procedure section then
calculate response factors using this equation,:
concentration of standard
RF -
area of standard
If the response factors are constant over the
working range (105 Relative Percent Difference), an
average response factor may be used for calcu-
lations .
6 . Quality Control.
6.1. Interference -- a water blank must be run with each
test to check for system contamination. A blank
should also be run between sanples of high concen-
tration .
6.2 Purity -- reagents used in the procedure should also
be analyzed with each test to determine their
purity,
4
B-fa
-------
6.3 Spikes -- sample matrixes should be spiked with the
compounds of interest and a percent recovery calcu-
lated to aceess'-matrix effects and method accuracy.
6.4. Duplicates -- Some samples should be analysed in
duplicate and a relative percent difference calcu-
lated to access aethod precision.
7 . Procedure.
7.1. Calibration as in section 5.
7.2. Sample Preparation -- allow samples to come to room
temperature before handling. Dilute if necessary to
"bring concentrations within system working range "by
adding portion of sample to water or to methylene
chloride if corn oil "based.
7.3. Analysis -- introduce sample by direct injection of
1 - 2 yl into the GC injection pert and begin the
temperature program.
' 7.4 Identification -- as the compounds are analysed
individually, there should be no coelution inter-
ferences. Retention time should still "be checked
against the standard.
3 . Calculation.
8.1. Concentration -- calculate using peak area and RF
determined in section 5.1.
B-?
-------
S.2. Dilution -- "ake into account any dilution perfo-rned
on the sample or the standard.
8.3 Report results in mg/ml without correction, for
recovery percentage.
B-8
-------
Final Report
Study No, 5221.07
APPENDIX C
CLINICAL CHEMISTRY MEHHODODDGY
97
C-l
-------
Cyanmethexnoglobin method
Baker Cell Counter
Hexnatology Series 7000
Hematccrit
Indirect method; calculated value based on erythrocyte-
count and mean corpuscular volume
Baker Cell Counter
Heraatolcgy Series 7000
ErytJirocyte Count
Electronic Counting Procedure
Baker Cell Counter
Hematolcgy Series 7000
Mean Corpuscular Volume fMCV)
Electronic Sizing Procedure
Baker Cell Counter
Hetnatology Series 7000
Mean, Corpuscular Hemoglobin .._(MCH1
Indirect method; calculated value based on erythrocyte
count and hemoglobin
Baker Cell Counter
Hematology Series 7000
Meanj5gro^cular Hemoglobin Concentratign_fMCHC)
Indirect method; calculated value based on hematocrit
and hezrjoglcbin
Baker Cell Counter
Heiaatolcgy Series 7000
Leukocyte Count
Electronic Counting Procedure
Baker Cell Counter
Hematology series 7000
CFM.MC c-2
-------
Leukocyte Differential Count
Neutrophils - Immature (bands)
Neutrophils - Mature (sags)
Mbnocytes
Basophils
Lymphocytes
Eosinophils
Wright stain procedure
Schalm, O.W., Jain, N.C. and Carroll, E.J.
Veterinary Hematology, Color Plates Chapter,
3rd Edition, lee and Febiger, 1975.
Reticulocyte Count
New methylene blue staining procedure
Brecher, G. Am. J. Clin. Path. 19,
895, 1949.
Prothrcrtibin Time (FT)
Rate of change in absorbance due to clot formation
Coag-A-Mate
Activated_Partial Throirfcoplasttn Time (APTT)
Rate of change in absorbance due to clot formation
Coag-A-Mate
ajNICAL CHEMISTRY
Creatinine
Jaffa's alkaline picrate reaction
Centrifichem Centrifugal Analyzer System
Fabiny, D.L. and Ertingshausen, G.
Clin. Chem., 17, 696, 1971.
Inorganic Riosphorus
Hiosphcmolyfadate reaction
Centrif ichem Centrifugal Analyzer System
Daly, J.A., and Ertinghausen, G.
Clin. Chem., 13, 263, 1972.
CTM.MC
q Q
•j o
C-3
-------
Glucose
Hejeokinase method
Centrifichem Centrifugal Analyzer System'
Bandar, J.L. and Mead, D.C.
din. Chem. 20, 586, 1974.
Urea Nitrogen (BUN)
Mbdif ied urease technique
Centrifichem Centrifugal Analyzer System
Talke, H. and Schubert, G.E.
Klin. Wchnschr. 43, 174, 1965.
Total Protein
Biuret technique
Centrifichem Centrifugal Analyzer System
Kingsley, G.R., J. Biol. Chem. 131, 197, 1939.
Albumin
Bromccresol Green method
Centrifichem Centrifugal Analyzer System
Doumas, B.T. and Biggs, H.G.
Standard Methods of Clinical Chemistry, 7, 175, 1972.
Globulin
Total Protein - Albumin = Globulin (Calculated value).
Calcium
Modified alizarin procedure
Centrifichein Centrifugal Analyzer System
Frings, C.S., et. al.f Clin, Chen., 16, 816, 1970.
Aspartate, Amino Transferase (AST/SGOT)
Modified Karnen procedure
Centrifichem Centrifugal Analyzer System
Bergmeyer, H.V., Schelbe, P., and Wahlefeld, A.W.
Clin. Chera., 24, 58, 1978.
Alanine Amino Transferase (ALT/SGPT)
Modified Henley & Pollard procedure
Centrifichem Centrifugal Analyzer System
Bergmeyer, H.V., Scheibe, P., and Wahlefeld, A.W.
Clin. Chem., 24, 58, 1978.
CTM.OC
C-4
io
-------
Alkaline Phosphatase
Modified Bowers-McCorb procedure
Centrifichem Centrifugal Analyzer System
Bowers, Jr., G.N., McComb, R.B.
Clin. Chem., 12, 70, 1966.
Cholestsrol
Allain enzymatic procedure
Centrifichem Centrifugal Analyzer System
Allain, C.C., et. al., Clin. Chem. 20, 470, 1974.
Total Bilirubin
Diazo colorimetric procedure
Centrifichem Centrifugal Analyzer System
Ertinghausen, G., Fabiny-Byrd, D.L., Tiffany, T.O.,
and Carey, S.J., Clin. Chem. 19, 1366, 1973.
Direct Bilirubin
Diazo colorimetric procedure
Centrifichem Centrifugal Analyzer System
Ertinghausen, G., Fabiny-Byrd, D.L., Tiffany, T.O.,
and Carey, S.J., Clin. Chem. 19, 13G6, 1973.
Electrolytes (Na+, K+, Cl~, C02)
Ion specific electrodes (Metpath, Inc.)
UKENALYSE5
Qualitative Measurements
pH Ketones Urobilinogen
Protein Bilirubin
Glucose Blood
Chemstrip 7L - Chemistry Reagent Strips
Bio-Dynamics/bmc
Indianapolis, Indiana
C5
C3M.MC C"5
-------
Specific Gravity
Optical tenperature compensated refractorneter
Microscopic Evaluation
Urinary sediment stained with Sedi-stain and evaluated using the Ames
Atlas of Urine Sediment, Ames Co., Division Miles Laboratories, Elkhart,
Indiana.
^ 0 9
dM.MC C-6 '* ^
-------
Final Report
Study No. 5221.07
APPENDIX D
INDIVIDUAL ANIMAL DAIA
D-l
-------
Study Ho. 5221.07
O
I
M
0)
DISPOSITION OF ANIMALS i« 13-UEEK HETA-CRESOL STUDY 1« SPRAGUE OAMLEY RATS
Dose Level
Cmg/ki/day)
0
50
150
450
0
50
150
450
*
Baseline Clinical
Sex Pathology Animals8
10/2/85
M
M
H
H
M 3521 -3530
F
F . -
F
F
F 3651 -3660
45-Day Sacrifice
11/1B-11/19/85
3401-3410
3431-3440
3461-3470
3491-3500
-
3531-3540
3561-3570
3591-3600
3621-3630
-
90-Day Sacrifice
1/2-1/4/86
3411-3430
3441-3460
3471 -3490
3501-3520b
-
3541-3560
3571-3590
3601-1620
3631-3650
-
* Animals selected for baseline clinical pathology were discarded without necropsy after the collection of blood
sanples.
b Early death, animal runtoer 3504 on 10/7/85.
O
-------
Study No. 5221.07
SUBCHRDNIC TOXICm OF MEI&-CRESOL
IN SERAGUE DftWLEY SMS
MEEEVIMTON CDDES
Body Weights and Food Consumption
ISAC - interim sacrifice
na - no data available
dead - unscheduled death
Organ Weights
e - raw data entry error
na - no data available
dead - unscheduled death.
term. wgt. - terminal bcdy weight
Urinalysis
c - clear
cl - cloudy
hz - hazy
y - yellow
py - pale yellow
ly - light yellow
a - amber
dy - dark yellow
s - straw color
tp - triple phosphate
co - calcium oxalate
ap - amorphous phosphate
n - none
tr - trace
m - many
f - few
ng - negative
nr - normal
mod - moderate
nura — numerous
Hematology & ....Clinical Chemistry
QNS - quantity not sufficient
dead -..unscheduled death
z - no clot was formed
sc - specimen clotted
thy ./para. - thyroid/parathyroid
rt - right
1ft - left
occ
>
dead
app
vol
uro
bili
ery
RBC/HEF
WBC/HPF
Casts/LPF -
EPI/HPF
occasional
greater than
unscheduled death
appearance
volume
urcbilinogen
.bilirubin
erythrocytes
number of red blood cells
under high pcwer field
number of white blood cells
under high power field
number of casts under low
pcwer field
number of epithelial cells
cells under high power
field
D-2
JLUO
-------
Study No. 5221.07
SUBCHRQMIC TOX1CITY OF HETA-CRESOU IN SPRAGUE DAWIEY RATS
MALE SODY WEIGHT DATA Cg)
ANIMAL NO. WEEK 1 WEEK Z WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3424
3427
3428
3429
3430
3431
3432
3433
3434
3435
3436
3437
343B
3439
3440
3441
3442
3443
3444
3445
3446
233
207
228
216
211
212
220
209
210
234
236
240
221
229
217
195
217
205
227
202
249
221
219
21S
225
213
226
211
218
225
233
228
215
216
205
213
234
212
233
196
204
225
186
229
205
223
297
271
291
277
280
270
274
271
269
305
311
313
286
287
278
253
297
264
296
246
317
303
285
282
2S4
264
283
274
273
284
295
292
283
280
262
278
302
272
298
238
267
293
262
301
263
273
343
320
346
318
331
314
313
312
322
363
373
374
337
333
330
292
361
311
345
276
372
377
335
327
341
308
335
333
320
329
340
359
329
321
306
322
355
322
342
290
308
346
304
354
306
324
394
361
392
360
376
356
352
350
360
415
403
432
375
370
381
324
397
355
400
314
423
437
384
372
373
353
372
364
353
358
383
412
372
367
332
355
393
356
381
322
334
389
338
390
345
363
431
391
432
391
400
3B9
387
386
394
460
452
465
413
412
419
360
444
383
435
346
453
439
396
410
413
395
408
391
392
396
419
455
415
410
365
394
420
390
403
356
363
434
374
413
381
394
465
424
456
417
431
414
409
404
418
482
484
491
444
449
447
3S8
471
415
470
364
493
530
430
446
447
413
437
426
419
418
448
492
441
431
392
426
454
420
437
381
376
467
397
441
416
419
491
454'
493
439
460
432
435
432
443
510
508
522
478
473
487
415
499
446
492
383
511
572
465
474
472
433
459
452
446
441
472
520
474
447
415
456
479
448
460
402
401
489
430
475
448
440
D-3
•* f\ P
L U t)
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE DAWLEY RATS
HALE BODY WEIGHT DATA (g)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 UEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
50 mgAg/day 3447
(continued) 3445
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
150 mg/kg/day 3461
3462
3463
3464
3465
3466.
346?
3468
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3431
3482
3433
34S4
3435
3486
3437
3488
3489
3490
180
216
224
221
226
224
217
231
227
220
213
231
198
231
219
215
230
208
224
224
226
221
203
210
223
207
226
225
222
202
235
224
225
231
225
229
234
211
206
208
235
225
222
213
235
278
292
288
288
290
276
301
302
283
236
311
269
303
279
263
299
262
293
297
282
233
254
272
273
276
288
283
296
252
300
234
291
291
257
313
301
270
270
270
301
291
233
272
272
323
348
333
341
345
335
354
347
330
334
370
324
, 358
332
316
344
297
340
341
318
342
291
320
309
330
337
333
313
291
344
325
335
333
327
365
358
314
317
285
338
345
334
321
297
369
393
370
375
394
368
403
386
373
366
412
360
404
377
355
388
332
381
378
354
389
322
358
341
383
378
374
356
317
388
367
380
370
370
407
404
357
354
328
371
388
364
351
332
394
426
402
412
432
404
419
419
413
401
449
393
431
342
334
423
353
416
403
393
360
355
395
361
417
409
407
391
342
420
407
417
394
400
440
442
382
389
363
394
415
403
354
365
420
460
432
443
466
423
451
443
443
423
493
423
463
382
408
445
374
441
421
417
405
367
410
376
432
420
428
402
352
433
434
441
406
433
466
450
410
403
383
405
433
413
397
396
441
496
454
458
498
442
436
471
475
446
529
453
495
434
431
466
386
477
446
445
460
387
434
393
456
446
460
421
372
462
463
461
427
465
498
486
433
422
417
426
449
411
436
D-4
->- f^
.L ()
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF HETA-CRESOL IM SPRAGUE DAULEY RATS
HALE BODY WEIGHT DATA Cg)
ANIMAL NO. WEEK 1 VfcEK 2 WEEK 3 WEEK 4 WEEK 5 UEEK & WEEK 7
DOSE LEVEL
450 tng/kg/day 3491
3492
3493
3494
3495
3496
3497
349S
3499
3500
3501
3502
3503
3504
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3513
3519
3520
205
223
217
222
231
197
217
202
209
241
229
199
227
213
237
211
239
. 219
222
226
229
2H
217
207
200
193
212
192
204
182
254
272
264
280
293
237
280
271
259
298
285
245
285
dead
290
254
302
272
283
293
296
266
273
245
251
223
261
242
254
227
289
310
312
325
342
267
319
305
341
345
331
287
326
-
338
301
353
315
323
341
343
301
311
239
293
253
297
235
300
261
314
343
348
366
376
304
353
329
381
372
360
310
364
-
381
395
396
370
384
385
3S7
347
332
331
359
289
328
324 "
324
293
335
373
370
396
413
309
389
357
414
406
380
334
382 '
-
398
357
434
287*
406
416
400
346
309
357
361
306
354
270*
344
307
358
401
394
425
437
344
420
395
453
442
416
355
416
-
430
394
471
364
439
447
438
376
369
390
384
331
390
343
• 375
333
331
424
424
456
469
370
453
418
470
462
441
372
447
-
444
414
503
409
445
471
477
403
386
422
409
357
413
373
401
357
* Signs of dehydration noted.
D-5
OS
-------
Study No. 5221.07
SUSCHRONIC TQX1C1TY OF META-CRESQL !M SPRAGUE OAULEt RATS
MALE BOOT WEIGHT DATA (g)
ANIMAL HO. WEEK a WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK U
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3401
3402
3403
3404
3405
3406
3407
34C8
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
3431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
1SAC
ISAC
1SAC
ISAC
I SAC
ISAC
ISAC
ISAC
ISAC
ISAC
532
553
501
499
510
442
527
466
522
397
542
618
491
501
494
451
486
479
469
461
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
417
508
460
506
464
466
na
na
na
na
na
na
na
na
na
na
533
579
503
524
509
457
549
481
545
410
566
640
513
522
509
459
496
499
483
484
na
na
na
na
na
na
na
na
na
na
431
528
488
514
479
479
na
na
na
na
na
na
na
na
na
na
567
596
535
540
534
479
575
496
558
426
583
660
529
547
534
469
, 516
525
501
511
na
na
na
na
na
na
na
na
na
na
452
554
513
537
502
507
na
na
na
na
na
na
na
na
na
na
589
608
546
556
556
489
581
516
586
434
603
679
550
567
547
492
527
531
516
484
na
na
na
na
na
na
na
na
na
na
473
581
530
560
534
523
na
na
na
na
na
na
na
na
na
na
616
631
542
571
573
509
615
531
601
445
632
707
563
578
569
498
557
551
535
506
na
na
na
na
na
na
na
na
na
na
483
593
524
569
544
531
na
na
na
na
na
na
na
na
na
na
630
631
546
585
586
513
628
543
607
450
633
711
580
588
583
515
559
556
544
523
na
na
na
na
na
na
nai
na
na
na
485
608
530
575
540
537
na
na
na
na
na
na
na
na
na
na
633
640
565
583
600
516
633
560
576
447
591
729
591
595
589
525
570
572
553
524
na
na
na
na
na
na
na
na
na
na
494
607
545
590
562
546
D-6
IOS
-------
Study No. 5221.07
SUBCHRONIC TOXIC!TY OF META-CRESOL IN SPRAGUE DAWLEY RATS
MALE BODY WEIGHT DATA, (g)
ANIKAl NO, WEEK 3 WEEK 9 WEES 10 WEEK 11 WEEK 13 WEEK 13 WEEK 14
DOSE LEVEL
50 mg/kg/day
(continued)
ISO mg/kg/day
3447
3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3481
3482
3483
3484
3485
3486
3487
3488
3489
3490
421
461
519
475
433
527
459
513
491
502
475
549
478
516
I SAC
I SAC
JSAC
I SAC
ISAC
I SAC
tSAC
ISAC
I SAC
SSAC
415
47S
473
476
397
389
486
489
483
397
486
521
513
449
401
431
403
474
445
409
451
471
542
498
502
546
469
539
313
524
496
576
491
551
na
na
na
na
na
na
na
na
na
na
433
499
485
499
427
409
503
510
504
419
508
546
535
469
435
452
339
502
469
456
472
494
569
521
523
560
SCO
545
528
550
521
594
505
543
na
na
na
na
na
na
na
na
na
na
448
532
517
523
415
428
534
537
481
469
536
567
561
499
469
468
406
533
501
434
506
510
589
S46
548
592
519
588
551
574
538
614
532
563
na
na
na
na
na
na
na
na
na
na
466
537
526
533
472
439
550
552
526
488
552
582
574
512
481
451
462
544
506
491
525
537
608
564
569
609
539
593
563
587
553
630
544
581
na
na
na
na
na
Ihl
na
na
r.:
na
488
553
536
566
504
450
549
574
548
509
563
602
539
526
502
440
486
564
518
506
536
537
619
577
569
610
544
598
572
588
554
634
555
595
na
na
na
na
na
na
na
na
• na
na
505
564
550
572
524
456
568
578
568
512
574
600
600
536
510
483
509
s&a
545
515'
554
545
627
594
578
625
536
612
579
596
561
637
567
597
na
na
na
na
na
na
na
na
na
na
502
566
551
544
505
428
563
575
547
484
550
606
604
542
487
455
506
560
514
493
D-7
110
-------
Study No. 5221.07
SU8CHRCH1C TQXICITT 0? HETA-CRESQL IN SPRAGUE DAULiT RATS
MALE BODY WEIGHT DAtA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 UEEK 11 WEEK 12 WEEK 13 WEEK 14
DOSE LEVEL
450 mg/kg/day
3491
3492
3493
3494
3495
3496
3497
3493
3499
3500
3501
3502
3503
3504
3505
3506
3507
3503
3509
3510
3511
3512
3513
3514
3515
3516
351?
3518
3519
3520
I SAC
ESAC
JSAC
ISAC
I SAC
ISAC
ISAC
ISAC
ISAC
ISAC
454
338
466
dead
399
432
523
437
476
445
505
409
398
437
369
372
429
398
414
361
na
na
na
na
na
r,a
na
na
na
na
464
401
479
-
453
440
539
455
4E1
362
526
421
417
442
389
380
436
4C5
424
369
na
na
na
na
na
na
na
na
na
na
491
427
474
_
477 .
• 453
563
437
504
385
551
437
444
463
429
406
458
430
438
389
na
na
na
na
na
na
na
na
na
na
498
431
491
_
500
462
579
488
522
481
. 560
450
459
483
452
416
456
445
452
409
na
na
na
na
na
na
na
na
na
na
515
447
512
_
515
473
602
511
545
520 ,
555
443
437
485
508
467
486
473
467
411
na
na
na
na
na
na
na
na
na
na
519
456
522
_
510
478
592
524
551
549
559
459
455
504
482
441
482
468
477
423
na
na
na
na
na
na
na
na
na
na
514
470
528
_
531
471
606
540
569
565
555
',39
465
512
4~5
445
484
47a
485
401
D-8
i
-------
Study No. 5221.07
SU8CHRDM1C TOXIC1TT Q? KETA-CRESOL IN SPRAGUE DAULEY RATS
MALE BOOT WEIGHT GA!M DATA (g)
ANIMAL NO. WEEK 1 UEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
0 mg/kg/day '
50 ing/kg/day
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
. 3421
3422
3423
3424
3425
3426
3427
3423
3429
3430
3431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
64
64
63
61
69
S3
54
62
59
71
75
73
65
58
61
58
80
59
69
44
68
62
66
£4
59
51
57
63
55
59
62
64
63
64
57
65
68
60
65
42
63
68
76
72
58
55
115
113
118
102
120
102
93
103
112
129
137
134
116
104
113
97
144
106
118
74
123
156
116
109
116
95
109
122
102
104
107
131
114
105
101
109
121
110
109
94
104
121
118
125
101
101
161
154
164
144
165
144
132
141
150
181
167
192
154
141
164
129
180
150
173
112
174
216
165
154
153
140
146
153
140
133
150
1S4
157
151
127
142
159
144
US
126
130
164
152
161
140
140
193
184
204
175
139
177
167
17?
184
226
216
22S
192
183
202
165
227
133
208
144
209
263
177
192
193
182
182
180
174
171
186
227
200
194
160
181
136
178
175
160
161
209
183
189
176
171
232
217
223
201
220
202
189
195
208
248
248
251
223
220
230
193
254
210
243
162
244
309
211
228
222
200
211
215
201
193
215
264
226
215
1S7
213
220
208
204
185
172
242
211
212
211
196
258
247
270
223
249
220
215
223
233
276
272
282
257
244
270
220
232
241
265
181
262
351
246
256
247
225
233
241
228
216
239
292
259
231
210
243
245
236
227
206
197
264
244
246
243
217
na
na
na
na
na
na
na
na
na
na
296
313
280
270
293
247
310
261
295
195
293
397
272
283
269
238
260
268
251
236
na
na
na
na
na
na
na
na
na
na
213
283
274
277
259
243
D-9
-------
Study No. 5221.07
SUBCHROHIC TOXtCm OF META-CRESOL IN SPRAGUE DAULEY RATS
MALE SCOT WEIGHT GAIN DATA (g>
ANIMAL NO. UEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 UEEK 7
DOSE LEVEL
50 mg/kg/day 3447
(continued) 3443
3449
3450
3451
3452
3453
3454
3455
3456
3457
345S
3459
3460
150 mg/kg/day 3461
3462
3463
3464
3465
3466
3467
3463
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3431
3482
3483
3434
3435
3486
3487
3488
3489
3490
55
62
63
67
62
66
59
70
75
63
63
80
71
72
60
53
69
54
69
73
56
67
51
62 •
55
69
62
63
74
SO
65
60
66
60
32
84
67
59
64
62
66
66
66
59
92
107
124
112
115
121
118
123
120
110
116
139
126
127
113
101
114
89
116
117
92
121
88
110
86
123
111
. 108
91
89
1D9
101
110
102
102
136
124
103
111
77
103
120
112
108
117
153
169
149
149
170
151
172
159
153
143
181
162
173
153
140
153
124
157
154
128
163
119
143
118
176
152
149
134
115
153
143
155
139
145
178
170
146
148
120
136
163
142
133
152
178
202
181
186
208
187
188
192
193
183
218
200
200
123
169
193
145
192
179
167
139
152
185
138
210
183
182
169
140
185
183
192
163
175
211
208
171
183
155
159
190
181
141
185
204
236
211
217
242
206
220
216
223
205
262
225
232
163
193
215
166
217
197
191
134
164
200
153
225
194
203
180
150
203
210
216
175
208
237
216
199
197
ITS
170
213
191
184
216
225
272
233
232
274
225
255
244
255
223
298
255
264
215
216
236
178
253
222
219
239
134
224
170
249
220
235
199
170
227
239
236
196
240
269
252
222
216
209
191
224
189
223
241
245
295
254
257
303
242
232
264
282
257
318
230
285
na
na
na
na
na
na
na
na
na
na
192
271
247
251
175
187
251
265
258
166
261
292
279
233
195
223
163
249
223
196
D-10 -f, -t 9
113
-------
Study No. 5221.07
SU8CHRQNIC TOX1CITY OF HETA-CRESOL IN SPRAGUE DAWLEY RATS
HALE BODY WEIGHT GAIN DATA (g)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
450 mg/kg/day
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
3501
3502
3503
3504
3505
3506
3507
3503
3509
3510
3511
3512
3513
3514
3515
3516
3517
3513
3519
3520
49
49
47
58
62
40
63
69
90
57
56
46
13
dead
53
43
63
53
61
67
67
52
56
33
51
25
49
50
50
45
84
87
95
103
111
70
102
103
132
104
102
S3
99
-
101
90
114
96
101
115
114
87
94
82
93
60
85
93
96
79
109
120
131
144
145
107
136
127
172
131
131
111
137
-
144
184
157
151
162
159
153
133
115
124
159
91
116
132
120
111
130
150
153
174
182
112
172
155
205
165
151
135
155
-
161
146
195
63
134
190
171
132
92
150
161
108
142
73
140
125
153
173
177
203
206
147
203
193
244
201
137
156
139
-
193
133
232
145
217
221
209
162
152
183
184
133
173
151
171
151
176
201
207
234
233
173
236
216
261
221
212
173
220
-
207
203
264
190
223
245
248
189
165
215
209
159
206
181
197
175
na
na
na
na
na
na
na
na
na
na
225
189
239
.-
162
221
289
213
254
219
276
195
131
230
169
174
217
206
210
179
D-ll
-------
Scudy No. 5221.07
SLIBCHROHIC TOXICITY OF META-CRESOL IN SPRAGUE DAULEt RATS
MALE BODY WEIGHT CAIN DATA (g>
ANIMAL NO. 'WEEK 3 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13
DOSE LEVEL
50 mg/kg/day
34Q1
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
3431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
na
na
na
na
na
na
na
na
na
na
317
339
282
295
292
262
332
276
318
208
317
419
294
304
284
246
270
288
265
259
na
na
na
na
na
na
na
na
na
na
227
303
302
285
274
256
na
na
na
na
na
na
na
na
na
na
331
356
314
311
317
234
358
291
331
224
334
439
310
329
309
256
290
314
233
236
na
na
na
na
na
na
na
na
na
na
248
329
327
308
297
284
na
na
na
na
na
na
na
na
na
na
353
368
325
327
339
294
364
311
359
232
354
458
331
349
322
279
301
320
298
259
na
na
na
na
na
na
na
na
na
na
269
356
344
331
329
300
na
na
na
na
na
na
na
na
na
na
380
391
321
342
356
314
398
326
374
243
3B3
486
344
360
344
285
331
340
317
281
na
na
na
na
na
na
na
na
na
na
279
368
338
340
339
303
na
na
na
na
na
na
na
na
na
na
394
391
325
356
369
318
411
338
380
248
384
490
361
370
358
302
333
345
326
298
na
na
na
na
na
na
na
na
na
na
281
383
344
346
. 335
314
na
na
na
na
na
na
na
na
na
na
397
400
344
354
383
321
416
355
349
245
342
503
372
377
364
312
344
361
335
299
na
na
na
na
na
na
na
na
na
na
290
382
359
361
357
323
D-12
115
-------
Study No, 5221.07
SUBCHROMIC TOXICITY OF META-CRESCL (M SPRAGUE DAULEY RATS
MALI BODY WEIGHT GAIN DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13
DOSE LEVEL
50 mg/kg/day 3447
(continued) 3443
3449
3450
3451
3452
3453
3454
3455
3456
3457
3453
3459
3460
150 mg/kg/day 3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3481
3482
3433
3484
3485
3486
3487
34SB
3489
3490
271
255
31S
277
276
322
252
308
286
304
278
345
293
320
na
na
na
na
na
na
na
na
na
na
210
292
259
274
205
207
268
2S6
279
188
283
317
301
258
229
244
104
277
247
243
292
278
345
300
297
336
283
314
301
330
303
363
307
312
na
na
na
na
na
na
ni
na
na
na
225
325
291
298
193
226
299
313
256
238
311
338
327
288
263
260
171
308
279
271
326
294
365
325
322
368
30Z
357
324
354
320
3S3
334
332
na
na
na
na
na
na
na
na
na
na
243
330
300
313
250
237
315
328
301
257
327
353
340
301
275
243
227
319
284
273
345
321
384
343
343
385
322
362
336
367
335
399
346
35Q
na
na
na
na
na
na
na
na
na
na
265
346
310
341
282
248
314
350
323
278
338
373
355
315
296
232
251
339
296
293
356
321
395
356
343
386
327
367
345
368
336
403
357
364
na
na
na
na
na
na
na
na
na
na
282
357
324
347
302
254
333
354
343
281
349
371
366
325
304
275
274
343
323
302
374
329
403
373
352
401
319
381
352
376
343
406
369
366
na
na
na
na
na
na
na
na
na
na
279
359
325
319
283
226
323
351
322
253
325
377
370
331
281
247
271
335
292
280
D-13
116
-------
Study No. 5221.07
SUBCHRONTC TOXICITY OF META-CRESOL IN SPRACUE DAULET RATS
HALE SOOT WEIGHT GAIN DATA (g)
ANIMAL NO. WEEK & UEEK 9 UEEK 10 UEEK 11 WEEK 12 WEEK 13
DOSE LEVEL
450 mg/kg/day
3491
3492
3493
3494
3495
3496
3497
3493
3499
3500
3501
3502
3503
3504
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
na
na
na
na
na
na
na
na
na
na
235
202
252
na
216
229
300
236
259
136
297
207
200
235
1B9
182
224
213
220
T87
na
na
na
na
na
na
na
na
na
na
262
223
247
na
240
247
324
268
282
159
322
223
227
256
229
203
246
233
234
207
na
na
na
na
na
na
na
na
na
na
269
232
264
na
263
251
340
269
300
255
331
236
242
276
252
218
244
253
248
227
na
na
na
na
na
na
na
na
na
na
286
243
285
na
273
262
363
292
323
294
326
229
220
278
308
269
274
281
263
229
na
na
na
na
na
na
na
na
na
na
290
257
295
na
273
267
353
305
329
323
330
245
238
297
282
243
270
276
273
241
na
na
na
na
na
na
na
na
na
na
2S5
271
301
na
294
260
367
321
347
339
326
255
248
305
245
247
272
2S6
281
219
D-14
-------
Study No. 5221.07
SUBCHiONIC TOXICITY OF HETA-CRESCU IN SPRAGU6 DAULEY RATS
FEMALE BODY WEIGHT DATA (g)
ANIMAL MO. WEEK 1 WEEK 2 UEEK 3 WEEK 4 WEEK 5 UEEK 6 WEEK 7
DOSE LEVEL
0 rag/kg/day
50 mg/kg/day
3531
3532
3533
3534
3535
3536
3537
3538
3539
3540
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3571
3572
3573
3574
357S
3576
162
137
148
156
156
139
132
136
152
133
150
162
127
134
142
144
137
139
139
150
130
160
150
146
145
153
168
160
157
142
128
155
154
149
137
150
162
144
152
145
155
154
161
140
148
152
187
169
181
186
186
166
159
167
189
160
176
1S7
154
170
179
168
172
169
169
181
163
193
188
169
164
183
190 "
190
182
174
165
175
179
181
180
179
197
172
172
169
186
183
192
166
178
190
216
189
202
208
205
182 .
178
188
213
173
196
209
175
191
201
188
195
191
196
208
182
216
214
188
177
200
216
209
198
192
189
195
201
199
201
197
221
186
188
192
208
207
209
184
198
210
232
202
220
232
225
192
194
213
238
202
214
229
191
211
217
205
229
210
211
218
199
215
241
209
189
226
240
226
218
211
201
213
219
207
220
220
241
205
210
202
227
227
230
202
213
228
247
215
225
241
246
2CS
201
222
258
222
233
240
200
222
226
224
238
230
228
237
223
240
264
224
209
243
248
238
226
226
224
232
232
227
232
230
255
218
225
214
246
237
247
223
228
246
255
229
234
259
253
215
211
239
267
233
251
249
213
232
232
218
252
250
217
252
233
251
241
239
• 218
248
262
248
234
233
233
240
239
239
213
243
272
223
240
225
253
251
266
223
237
255
268
233
245
276
262
230
225
247
283
247
258
261
224
246
249
248
- 259
263
244
264
246
256
273
250
227
251
276
256
239
236
239
247
251
256
223
255
282
243
250
234
261
265
269
238
242
267
D-15
•* 4 O
L L 6
-------
Study No. 5221.07
SUBCKRCMIC TOXJCiTY QF MSTA-CRESOL IN SPRAGUE OAULEY RATS
FEMALE BODY WEIGHT DATA (g)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
50 mg/ks/day 3577
(continued) 3578
3579
3580
3581
3582"
3583
3534
3585
3586
3587
3588
3589
3590
150 rag/kg/day 3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3601
3602
3603
3604
36Q5
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
157
145
158
143
149
161
153
158
160
139
137
172
168
138
152
159
156
163
141
158
153
146
119
149
159
142
152
141
151
151
142
145
134
146
162
162
14t
143
151
141
151
148
157
151
132
172
193
133
174
190
163
183
180
163
185
198
194
163
182
180
186
199
162
189
181 .
180
153
178
187
170
174
170
184
176
162
176
157
181
192
187
172
169
166
173
174
166
178
171
209
193
212 -
206
182
201
179
214
196
178
205
215
226
176
206
198
210
229
184
210
193
195
169
197 .
213
198
197
182
211
192
183
203
181
196
213
202
194
189
184
195
191
187
204
197
228
210
221
221
196
212
196
233
206
194
222
233
228
187
218
211
' 226
253
196
234
212
212
184
217
230
225
212
204
229
216
207
218
200
216
238
226
206
203
201
220
211
209
217
212
226
221
244
233
213
224
214
258
220
203
238
247
243
200
241
225
243
269
206
249
228
230
202
241
242
241
213
218
242
231
216
235
222
220
250
241
225
224
210
232
228
214
228
226
231
237
244
246
222
243
224
276
223
221
253
264
255
211
252
234
237
288
218
252
241
239
205
244
258
248
227
219
262
240
231
245
229
241
256
256
, 228
227
215
241
239
223
237
231
248
253
258
255
222
245
230
291
241
226
262
269
270
215
262
241
257
293
232
263
246
251
223
255
274
262
224
231
266
247
243
257
247
243
266
258
238
237
231
254
253
232
252
241
D-16
119
-------
Study No. 5221.07
SUBCHRONIC TOXICtTY OF META-CRESQL IN SPRAGUE DAULET RATS
FEMALE BODY WEIGHT DATA (9)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
450 mgAg/day
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
5644
3645
3646
3647
3648
3649
3650
160
136
143
144
145
163
159
156
147
136
145
150
123
136
132
147
154
134
147
154
134
159
136
132
151
150
140
154
164
148
185
157
171
172
172
173
181
182
171
160
152
180
152
161
162
177
175
161
167
173
153
194
173
143
136
161
130
137
194
176
206
179
196
192
190
195
202
266
192
176
170
198
173
186
183
199
191
176
181
188
171
219
197
158
203
133
204
212
221
193
230
201
202
217
207
210
221
222
211
196
177
216
180
203
202
230
217
198
195
215
190
247
220
177
218
210
219
230
241
220
247
210
227
233
224
222
234
233
222
209
186
227
185
222
214
240
226
215
203
220
200
270
224
179
228
218
227
237
243
226
267
224
240
253
235
237
247
244
240
223
192
235
196
237
228
256
230
230
201
224
206
277
241
192
243
235
242
261
261
227
275
232
259
247
241
244
258
250
251
231
203
249
199
255
234
272
239
243
218
241
217
296
256
196
255
250
254
275
275
236
D-17
120
-------
Study No. 5221.07
SUBCHRONIC TOXIC1TY OF META-CRESOL 1M SPSAGUE DAULEY RATS
FEMALE BODY WEIGHT DATA (g)
ANIMAL NO. UEEiC 8 UEEK 9 yEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK 14
DOSE LEVEL
0 nig/kg/day
50 mg/lcg/day
3531
3532
3533
3534
3535
3536
3537
3533
3539
3540
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3571
3572
3573
3574
3575
3576
1SAC
I SAC
1SAC
I SAC
I SAC
I SAC
ISAC
ISAC
ISAC
ISAC
263
268
232
245
251
265
263
272
256
271
253
266
283
259
232
264
283
266
243
248
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
279
268
2S5
252
255
274
na
na
na
na
na
na
na
na
na
na
274
266
233
250
261
264
279
235
256
279
254
263
265
261
235
272
283
278
241
247
na
na
na
na
na
na
na
na
na
na
283
273
290
253
256
280
na
na
na
na
na
na
na
na
na
na
281
269
242
260
267
264
273
296
266
281
263
276
300
274
249
275
300
286
245
253
na
na
na
na
na
na
na
na
na
na
284
274
292
261
265
284
D-18
na
na
na
na
na
na
na
na
na
na
291
283
256
259
275
280
289
303
278
2SS
280
290
315
286
252
288
306
288
253
258
na
na
na
na
na
na
na
na
na
na
301
287
295
280
273
296
na
na
na
na
na
na
na
na
na
na
291
274
257
272
271
226
287
306
275
293
291
287
305
293
251
292
302
289
248
266
na
na
na
na
na
na
na
na
na
na
305
284
312
284
283
305
na
na
na
na
na
na
na
na
na
na
300
266
250
270
273
284
288
316
273
291
295
302
299
288
255
304
303
293
264
269
na
na
na
na
na
na
na
na
na
na
308
286
310
289
284
310
j(
i
na
na
na
na
na
na
na
na
na
na
300
266
263
284
287
296
301
322
231
297
299
292
320
296
263
305
310
302
261
269
na
na
na
na
na
na
na
na
na
na
303
290
312
2sa
286
301
21
-------
Study No. 5221.07
SUBCHRCNIC TOX1CFTY OF META-CRESOL IN SPRAGUE DAULEY RATS
FEMALE BODY WEIGHT DATA (g>
ANIMAL HO. UEEK 8 WEEK 9 WEEK 10 WEEK 11 UEEK 12 UEEK 13 WEEK 14
DOSE LEVEL
50 mg/kg/day 3577
(continued) 3578
3579
3580
3581
3532
3583
3584
3585
3586
3587
3583
3589
3590
150 mg/kg/day 3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3601
36C2
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
269
261
256
258
233
251
222
292
247
236
266
275
278
222
I SAC
I SAC
I SAC
1SAC
I SAC
I SAC
I SAC
I SAC
I SAC
1SAC
230
273
225
236
271
262
252
274
251
253
277
270
241
241
235
255
266
241
223
244
253
267
250
260
227
257
241
302
253
235
271
276
281
231
na
na
na
na
na
na
na
na
na
na
286
285
241
241
278
260
256
282
260
257
283
2BO
243
239
237
239
280
239
243
250
256
271
264
269
229
256
245
312
252
242
237
280
280
241
na
na
na
na
na
na
na
na
na
na
289
286
250
252
244
272
265
298
268
230
290
295
253
255
245
268
293
246
273
227
274
288
262
282
244
263
256
330
266
257
295
298
287
243
na
na
na
na
na
na
na
na
na
na
305
303
257
251
255
281
268
299
271
241
300
292
262
256
251
275
302
261
283
235
273
288
275
285
249
263
256
319
273
253
288
292
297
246
na
na
na
na
na
na
na
na
na
na
309
306
262
262
291
274
305
273
309
265
306
263
285
319
259
279
232
265
251
265
263
294
' 275
284
260
268
257
326
266
260
292
297
304
246
na
na
na
na
na
na
na
na
na
na
296
309
253
264
280
269
274
315
277
264
295
303
263
257
250
272
331
258
263
267
277
307
287
286
260
273
262
337
274
260
300
298
302
245
na
na
na
na
na
na
na
na
na
na
307
317
237
275
292
261
326
288
314
316
276
272
288
271
257
288
341
267
279
263
D-19
•i 9 9
'
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF HETA-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE BODY WEIGHT DATA
-------
Study No. 5221.07
SUBCHROHIC TOXICITY OF META-CRESQi !H SPRAGUi DAWLEY SATS
FEMALE SQOr WEIGHT GAIN DATA (gj
ANIMAL NO WEEP: 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6. USES r
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3531
3532
3533
3534
3535
3536
3537
3538
3539
3540
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3571
3572
3573
3574
3575
3576
25
32
33
30
30
27
27
31-
37
27
26
25
27
36
37
24
35
30
30
31
33
33
38
23
19
30
22
30
25
32
37
23
25
32
43
29
35
28
20
24
31
29
31
26
30
33
54
52
54
52
49
43
46
52
61
40
46
47
48
57
59
44
53
52
57
58
52
56
64
42
32
47
43
49
41
50
61
40
47
50
64
47
59
42
36
47
53
53
48
44
50
58
70
65
72
76
69
53
62
77
86
69
64
67
64
77
75
61
92
71
72
63
69
55
91
63
44
73
'72
66
61
69
73
58
65
58
83
70
79
61
58
57
72
73
69
62
65
76
85
78
77
85
90
69
69
86
106
89
83
78
73
88
84
80
101
91
89
• a?
93
30
114
78
64
50
80
78
69
84
96
77
78
78
95
80
93
74
73
69
91
83
86
83
80
94
93
92
86
103
97
76
79
103
115
100
101
87
86
93
90
74
115
111
78
102
1D3
91
91
93
73
95
94
88
77
91
105
85
85
90
81
93
110
79
88
80
103
97
105
88
89
103
106
96
97
120
106
91
93
111
131
114
108
99
97
112
107
104
122
124
105
114
116
96
123
104
82
98
108
96
82
94
111
92
97
107
86
105
120
99
98
89
106
111
108
98
94
115
na
na
na
na
na
na=
na
na
na
na
113
106
105
111
109
121
126
133
117
121
123
106
133
113
87
111
115
106
86
106
na
na
na
na
na
na
na
na
na
na
124
114
124
112
107
122
1 9 4.
D-21 - ~ -
-------
Study No. 5221.07
SUBCHROMJC TOXICITY OF META-CRESOl IM SPRAGUE OAWLEY RATS
FEMALE BODY WEIGHT GAIN DATA (g)
AHIMAL NO WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
50 mg/kg/day 3577
{continued} 3578
3579
3530
35B1
3582
3583
3584
3585
3586
3537
35Sfl
3589
3590
150 mg/kg/day 3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
361B
3619
1 3620
25
27
35
40
25
29
10
25
20
24
48
26
26
25
30
21
30
36 ,
21
31
28
34
34
29
28
28
22
29
33
25
20
31
23
35
30
25
31
26
15
32
23
18
21
20
52
48
54
63
33
40
26
56
36
39
63
43
53
38
54
39
54
66
43
52
40
49
50
43
54
56
45
41
60
41
41
SB'
47
50
51
40
53
46
33
54
40
39
1,7
46
• 71
65
63
78
47
51
43
80
46
55
85
61
60
49
66
52
70
90
55
76
59
66
65
68
71
83
60
63
78
65
65
73
66
70
76
64
65
65
50
79
60
61
60
61
69
76
86
90
64
63
61
100
60
64
101
75
75
62
89
66
87
106
65
91
75
84
83
92
83
99
61
77
91
80
74
90
88
74
SS
79
84
81
59
91
77
66
71
75
74
92
S6
103
73
82
71
113
68
32
116
92
87
73
100
75
81
125
77
94
88
93
86
95
99
106
75
78
111
89
89
100
95
95
94
94
87
34
64
100
88
75
ao
80
91
108
100
112
73
84
77
133
81
87
125
97
102
77
110
32
101
130
91
105
93
105
104
106
115
120
72
90.
115
96
101
112
113
97
104
96
97
94
80
113
102
84
95
90
92
116
98
115
84
90
69
134
87
97
129
103
110
84
na
na
na
na
na
na
na
na
na
na
121
131
73
95
120
111
110
129
117
107
115
108
100
98
84
114
115
93
66
93
D-22
125
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CftESOL IN SPSAGUE DAULEY RATS
FEMALE BODY UE1GHT GAIN DATA (9)
ANIMAL NO WEEK 1 WEEK 2 WEEK 1 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
450 mfl/kg/day
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
364&
3641
3642 '
3643
3644
3645
3646
3647
3648
3649
3650
25
21
23
28
27
10
22
26
24
24
7
30
24
25
30
30
21
27
20
19
19
' 35
37
16
35
11
40
33
30
28
46
43
43
43
45
32
43
110
45
40
25
43
45
50
51
52
37
42
34
34
37
60
61
26
5-2
33
64
58
57
45
7Q
65
54
73
62
47
62
66
64
60
32
66
52
67
70
83
63
64
48
61
56
88
84
45
67
60
79
76
77
72
87
74
79
89
79
59
75
77
75
73
41
77
57
86
82
93
72
81
56
66
66
111
88
47
77
68
67
83
84
78
107
88
92
109
90
74
83
83
93
87
47
85
68
101
96
109
76
96
54
70
72
118
105 "
60
92
85
102
107
97
79
115
96
111
103
96
81
99
94
104
95
58
99
• 71
119
102
125
85
109
71
87
83
137
120
64
104
100
114
121
111
88
na
na
na
na
na
na
na
na
na
na
62
104
68
119
95
116
87
119
74
eo
85
150
115
71
104
100
104
124
115
86
D-23
•* a f*
1 ,i I)
-------
Study No, 5221.07
SUBCHRON1C TOXIC1TY OF META-CRESCL IN SPRAGUE OAULEY RATS
FEMALE 80DV WEIGHT GA1H DATA
-------
Study No. 5221.07
SUBCHRQHIC TCXtCITY OF HETA-C8ESQL IN SPRAGUE DAULEY RATS
FEMALE 100* WEIGHT GAIN DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 UEilC 11 yEEK 12 WEEK 13
OOSE iEVEL
50 mg/kg/day 3577
(continued) 3578
3579
3580
3581
3582
3583
3584
3585
3586
3587
3588
3589
3590
150 mg/kg/day 3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
96
122
92
117
78
96
88
144
98
96
134
104
113
93
na
na
na
na
na
na
na
na
na
na
127
143
89
100
127
109
114
137
126
111
121
118
102
96
86
118
129
91
91
99
99
126
106
126
ao
95
92
154
92
103
150
108
112
103
na
na
na
na
na
na
na
na
na
na
130
144
98
111
93
121
123
153
134
84
128
133
117
112
94
127
147
98
116
76
117
143
104
139
95
102
103
172
106
113
158
126
119
105
na
na
na
na
na
na
na
na
na
na
146
161
105
110
104
130
126
154
137
95
132
130
121
113
100
134
151
113
126
84
116
143
117
142
100
102
103
161
113
114
151
120
129
108
na
na
na
na
na
- ia
na
na
' a
na
150
164
110
121
140
123
163
128
175
119
144
101
144
176
108
138
131
117
94
114
111
149
117
141
111
107
104
168
106
121
155
125
136
108
na
na
na
na
na
na
na
na
na
na
137
167
101
123
129
118
132
170
143
118
133
141
122
114
99
131
180
110
111
116
120
162
129
143
111
112
109
179
114
121
163
126
134
107
na
na
na
na
na
na
na
na
na
na
148
175
85
134
141
110
184
143
180
170
114
110
147
128
106
147
190
119
122
112
D-25
-------
Study No. 5221.07
SUBCHRONIC TOX1CITY OF META-CRESOl IN SPRAGUE DAWIEY RATS
FEMALE BODY WEIGHT GAIN DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WtEK 12 WEEK 13
DOSE LEVEL
450 ng/kg/day
3621
3622
3623
3624
3625
3626
3627
3623
3629
3630
3631
3632
3633
3634
3635
3636
3637
363S
3639
3640
3641
3642
3643
3644
3645
3646
3647
3648
3649
3650
na
na
na
na
na
na
na
na
na
na
62
103
74
131
102
122
96
113
68
84
89
151
122
70
104
107
118
132
125
90
na
na
na
na
na
na
na
na
na
na
70
113
81
142
102
130
101
125
71
83
95
159
125
77
115
69
137
144
141
67
na
na
na
na
na
na
na
na
na
na
82
119
79
142
111
135
100
132
73
87
104
163
125
78
126
109
142
150
142
100
na
na
na
na
na
na
na
na
na
na
73
124
90
146
125
145
113
134
77
94
93
165
128
82
136
120
150
159
151
113
na
na
na
na
na
na
na
na
na
na
80
127
98
143
130
151
110
141
SA
109
94
164
124
90
133
79
162
169
159
118
na
na
na
na
na
na
na
na
na
na
97
134
73
157
120
162
109
131
84
98
109
204
120
84
141
121
150
176
151
113
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-C8ESOI IN SPRAGUE DAULEY RATS
KALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 1 old 1 new 2 old 2 new 3 old 3
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
3431
3432
3433
3434
3435
3436
3437
3433
3439
3440
3441
3442
3443
3444
3445
3446
604.1
590.3
615.0
618.4
536.9
564.5
651.7
597.2
596.4
585.1
656.7
640.4
611.1
618.6
600.0
646.0
610.4
605.9
570.0
613.8
615.5
590.5
527.9
626.2
556.2
603.3
666.7
648.4
638.0
590.8
630.0
647.3
594.8
599.6
629.1
657.2
622.9
636.6
648.5
632.3
637.3
624.6
667.8
639.3
668.8
475.6
386.1
409.4
424.7
435.3
361.8
381.7
480.2
415.6
411.8
381.8
444,6
440.4
423.5
439.0
4C9.5
471.7
399.9
439.0
376.2
443.4
388.9
372.3
340.1
431.3
372.8
430.5
482.7
462.7
409.6
378.8
430.1
463.0
414.7
423.8
458.2
467,3
423.0
463.0
467.6
469.7
467.4
442.0
493.1
427.3
569.2
475.1
474.3
507.8
551.4
549.4
508.8
500.3
586.0
504.4
523.5
499.2
544.1
528.8
505.0
498.3
546.1
530.0
494.1
546.7
485.6
520.1
509.8
464.2
475.8
558.3
493.0
566.6
577.4
511.1
527.6
535.0
490.0
509.9
496.9
518.7
527.2
480.1
489.7
502.5
499.3
504.9
511.3
504.4
501.0
508.5
550.4
588.6
250.8
335.1
344.3
371.5
319.4
322.2
414.8
310.8
332.8
283.5
324.4
302.3
307.5
315.5
345.8
409.6
270.7
363.3
286.2
356.1
280.5
232.2
282.9
359.1
263.4
393.4
371.8
315.7
320.9
309.3
294.0
299.9
310.8
350.6
359.6
300.7
291.0
311.0
327.2
336.6
348.6
313.3
317.9
358.5
400.7
413.9
472.1
492.9
483.9
519.1
479.4
473.6
540.5
445.7
487.9
491.0
467.3
482.6
488.0
470.9
477.9
474.5
445.8
494.5
459.8
507.3
478.8
437.0
454.2
501.1
438.0
489.8
483,7
442.7
476.2
462.8
435.5
439.2
451.0
499.5
468.7
422.9
420.5
466.0
460.2
485.9
486.1
463.4
452.5
461.0
436.6
480.7
250.3
317.2
283.0
326.1
275.6
305.6
337.1
254.5
302.2
272.0
273.1
259.0
296.7
280.4
273.0
304.2
249,2
315.3
254.2
337.0
271.3
211.4
260.2
309.8
253.0
308.7
295.1
263,6
231.7
263.1
265.9
217.7
251.0
317.1
232.7
251.4
251.6
250.9
310.2
250.9
332.7
220.9
261.8
274.2
241.8
Z98.8
D-27
130
-------
Study No. 5221.07
SUBCHRCNIC TOXICm OF MiTA-CRESOL IN SPRAGUH DAULEY RATS
MALE FOOD CQNSUHPTiOK DATA (g)
[Feeder Ueightsl
ANIMAL NO. new 1 old 1 new 2 old 2 new 3 old 3
50 mg/fcg/day 3447
(continued! 1443
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
150 log/kg/day 3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3481
3482
3483
3484
3485
3486
3487
3488
3489
3490
* Invalid weight.
652.
642.
648.
522.
674.
575.
6SO.
423.
664.
477.
•6flO.
671.
625.
640.
6S4.
552.
518.
623.
617.
597.
668.
489.
502.
569,
577.
512.
576.
594.
499.
498.
591.
565.
576.
470.
473.
478.
8
T
9
4
9
6
3
1
2
2
5
8
4
2
5
7
8
5
8
0
2
2
2
5
7
9
5
1
6
6
7
6
2
6
1
4
464.3
536.
492.
450.
517.
431.
473.
490.
2
0
4
,2
9
4
3
502
479
337
.2
.0
.5
483.7
469
465
501
475
429
458
517
469
445
451
504
381
338
459
419
403
469
300
335
373
407
329
400
425
298
354
379
380
33S
275
315.
276
274
372
328
280
331
241
272
309
.8
.5
.3
.1*
.1
.2
.5
.7
.4
.3
.6
.7
.4
.1
,8
.1
.7
.0
.4
.3
.0
,8
.3
.4
.2
.3
.2
.1
.4
.1
.8
.6
.5
.9
.3
.5
.6
.2
.9
.2
i
624
615
445
620
503
.8
.0
.9
.2
.1
496.7
507
541
531
541
534
541
515
515
516
481
471
514
496
483
496
449
431
496
483
438
481
486
430
467
458
480
4S4
484
487
490
494
499
472
474
457
459
432
470
r»_9i
.1
.1
.0
.5
.7
.8
.0
.7
.0
.0
.8
.9
.7
.5
.0
.4
.9
.4
.4
.5
.7
.6
.3
.1
.4
.0
.8
.2
.3
.3
.6
.7
.3
.7
.5
.7
.0
.1
R
492.9
445.4
252.5
436.5
317.2
301.4
318.0
340.6
348.3
362.9
364.1
332.5
339.1
326.1
308.6
279.9
273.0
335.6
250.8
286.3
288.4
251.4
252.4
286.0
331.7
223.9
300.5
311.2
220.6
31S.6
254.6
293.9
281.3
291.6
286.9
283.0
291.4
324.2
291.2
352.2
276.3
257.9
236.2
276.2
492
47T
.9
.1
422.7
455
427
439
454
439
448
436
480
.2
.1
.5
.2
.7
.0
.6
.4
466.7
459
.3
479.8
450
411
441
483
495
434
448
432
457
448
437
422
447
457
418
436
439
445
442
440
440
427
441
483
433
445
422
.1
.7
.4
.0
.2
.0
.4
.8
.1
.8
.7
.9
.0
.?
.6
.7
.7
.7
.3
.4
.3
.8
.2
.0
.5
.2
.8
404.7
413
446
.9
.4
253
309
230
279
251
251
273
265
267
256
323
276
293
275
251
249
271
327
306
251
250
236
281
319
333
264
293
265
261
307
375
256
252
152
264
252
252
252
256
266
251
210
269
247
.8
.6
.8
.9
.9
.4
.7
.8
.2
.2
.4
.1
.4
.8
.2
.3
,3
.8
.1
.6
* "*
.0
.0
.a
.5
.1
.3
.0
.8
.5
.0
.9
.2
.6
.9
.1
.6
.7
.8
.6
.4
.0
.3
.9
1 O'-J
-i. O JL
-------
Study No. 5221.07
SUBCHRONIC TOXICITY 0? HETA-CRESOL IN SPRAGUE DAULEY RATS
HALE FOOD CONSUMPTION DATA (g)
CFeeder Weights]
ANIMAL NO. new 1 old 1 new 2 old 2 new 3 old 3
DOSE LEVEL
450 mg/lcg/day
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
3501
3502
3503
3504
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
• 3515
3516
3517
3513
3519
3520
362.0
524.9
546.8
393.1
450.0
533.9
S27.7
498.9
480.4
475.8
570.0
453.6
447.4
381.9
511.3
392.7
476.0
530.7
467.8
422.7
461.6
331.5
407.1
370.4
519.2
537.6
457.5
403.fi
385.2
439.3
216.6
355.0
373.3
214.3
262.9
383.9
355.4
339.3
281.8
301.5
397.9
310.5
289.3
dead
326.6
252.6
290.8
341.5
292.5
256.4
286.7
218.7
257. Q
234.3
362.5
412.4
302.3
245.7
241.3
350.6
434.7
482.7
491.7
476.1
540.0
733.4
415.9
478.7
465.9
433.1
413.9
435.4
502.5
-
467.6
505.0
503.4
474.4
530.2
497.3
521.1
444.4
503.4
495.7
550.6
594.2
529.6
505.2
572.7
461.4
271.7
294.5
287.0
263.2
324.2
578.8
224.9
293.0
262.4
238.9
224.4
261.7
308.5
-
247.2
350.9
307.9
296.2
344.3
309. B
333.1
287.2
339.6
340.9
381.3
454.8
371.3
334.0
405.9
326.3
445.3
453.8
452.4
425.9
463.5
448.3
464.5
433.0
412.8
433.9
438.7
417.8
455.7
_
389.4
443.1
447.4
456.3
438.2
461.8
421.8
445.5
445.4
444.9
491.1
493.7
459.3
42S.1
432.1
455.9
279.3
296. a
299.7
256.3
235.7
308. 3
299.4
290.7
229.0
291.1
228.2
231.1
304.5
_
216,9
283.3
239.6
277. 4
233.8
266.9
236.8
299.1
307.1
306.3
323.6
344.5
233.3
254.9
277.3
315.9
D-29
100
1
-------
Study No, 5221.07
SUBCKRCNIC TOXIC ITY OF META-CRESOL IH SPMGUE DAWLET RATS
MALE FOOT CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 4 old 4 ne« 5 old 5 new 6 old A
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3414
3417
3418
3419
3420
3421
3422
"423
3424
3425
3426
3427
3428
3429
3430
3431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
550.4
562.2
538.6
590.9
541.5
494.6
545.8
.575.8
531.8
541.3
555.8
556.7
586.4
577.0
564.2
553.4
593.5
583.7
546.0
590.0
575.9
486.8
483.1
585.0
554.7
569.8
618.9
580.2
581.7
582.1
601.1
493.2
500.4
580.1
540.9
596.8
546.5
611.7
568.2
599.4
560.9
570.5
554.0
563.3
487,1
548.7
329.9
388.7
338.4
407.6
370.4
322.9
356.5
391.5
351.1
326.2
333.6
350.2
393.7
374.1
360,9
373.5
" 381.3
40H.9
342.2
416.6
331.1
229.9
331.3
333.3
343.9
370.8
426.2
404.4
367.3
354.6
358.9
362.5
336.4
376.1
325.8
422.4
364.0
399.7
423.2
426.1
378.1
304.8 •
330.4
384.3
340.6
359.9
'474.9
493.3
491.1
463.9
497.6
478.8
482.2
466.6
469.0
511.8
508.6
505,7
512,7
506.7
509.7
489.9
511.2
513.5
505.5
536.0
574.0
523.9
483.0
507,7
521.8
505.9
497.9
510.3
491.5
488.1
516,0
490.2
490.2
493.3
469.0
481.9
513.0
497.9
529.9
530.3
495.2
508.0
481.2
505.6
485.5
502.9
260.3
325.6
299.9
284.3
328.7
322.3
304.0
297.4
294.2
319.2
298.1
307.0
319.2
311.7
311.8
310.7
319.1
331.0
326.1
396.9
377.4
304.4
321.9
319.6
254.0
340.2
321-0
338.8
274.6
285.9
325.0
304.9
340.3
405.2
410.1
335.9
351.9
375.8
377,3
385.9
354.9
344.2
349.3
392.3
311.6
369.4
486.7
483.8
498.7
482.0
476.0
483.3
471.4
477.5
466.9
478.2
474.0
469.8
487.2
482.4
482.3
471.5
489.8
489.2
493.6
497.8
499.8
471.7
487.2
49Q.9
476.2
473.8
486.1
475.8
484.4
470.8
475.1
483.3
447.1
483.8
469.4
464.5
480.4
478.8
489.2
491.4
476.7
454.2
480.4
474.2
476.7
476.9
286.0
305.0
319.8
324.2
309.3
324.9
302.9
308.7
298.2
288.3
276.8
282.0
308.1
288.7
289.1
294.6
289.0
313.0
318.4
327.3
273.4
214.8
294.6
319.6
274.1
316.5
318.6
328.8
2S9.9
268.6
281.6
275.1
294.9
277.2
326.5
297.4
277.2
300.3
312.5
316.0
340.0
314.0
306.4
292.0
304.0
286.4
D-30 133
-------
Study No. 5221.07
SU8CHRON1C TOXtClTY OF HETA-CS6SOL IH SPRAGUE OAUIEY RATS
KALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIKAL NO. new 4 oEd 4 new 5 old 5 new 6 old 6
DOSE LEVEL
SO mg/ks/day 344?
(continued) 3448
3449
3450
3451
3452
3453
34S4
3455
3456
3457
3458
3459
3460
150 mg/kg/day 3461
3462
3463
3464
3465
3466
3467
3463
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3481
3482
3483
3484
3485
3486
3487
3488
3489
3490
550.
532.
489.
601.
569.
564.
550.
556.
538.
569.
588.
585.
562.
552.
531.
599,
586.
576.
514.
601.
574.
590.
598.
598.
542.
574.
569.
575.
519.
544.
550.
527.
552.
587.
567.
577.
566.
546.
578.
512.
526.
536.
559.
480.
2
0
4
2
9
8
6
9
8
0
6
1
9
3
2
7
5
5
a
7
6
0
6
6
9
7
7
8
6
4
1
5
5
5
5
1
3
3
3
6
6
9
3
8
410
362
290
419
379
353
374
367
357
382
413
352
' 389
365
527
315
298
409
351
432
354
539
405
414
406
382
368
382
300
401
357
348
360
399
404
381
366
369
391
352
362
329
367
360
.3
.4
.3
.1
.7
.9
.0
.1
.1
.5
.4
.7
.8
.2
.0
.0
.6
.8
.9
1
.4
.2
,9
.3
.1
.2
.3
.5
.4
.7
.2
.6
.2
.7
.5
.9
.7
.6
.8
.6
.3
.8
.8
.7
530
559
528
.5
.5
.1
518.5
546
575
536
542
502
516
535
523
519
497
467
494
495
547
567
595
582
539
557
534
575
492
539
594
432
476
546
539
555
514
545
534
558
516
528
497
516
492
527
447
.7
.7
.6
.1
.2
.6
.7
.5
.5
.3
.6
.7
.7
,6
.1
.1
.2
.2
.3
,6
,4
.9
,3
.0
.7
.7
.9
.4
.0
.7
.4
.1
.8
.9
.0
.8
.1
.4
.2
.9
315
323
280
312
325
300
320
321
326
363
364
360
269
311
307
367
298
281
279
304
301
310
387
370
338
310
335
295
318
300
322
300
386
309
336
283
303
360
295
3C9
287
294
307
341
.2
.3
,0
.5
,1
.5
.1
.5
.1
.9
.8
.9
.1
.2
.5
.0
.9
.6
.6
.9
.9
.5
.0
.1
.9
.2
.7
.8
.3
.7
.0
.3
.7
.0
.9
.6
.4
.6
.5
.5
.8
.5
.6
.8
492.
478.
478.
477.
438.
479.
467.
480.
474.
475.
470.
481.
459.
477.
426.
447.
414.
418.
411.
417.
413.
414.
448.
469.
410.
422.
411.
411.
421.
417.
416.
421.
461.
417.
7
3
a
2
3
8
3
6
1
2
9
9
7
6
4
3
9
3
9
4
9
9
1
7
3
6
7
9
7
3
8
3
4
3
423.7
444.
427.
426.
423.
441.
449.
443.
439.
440.
9
5
8
0
1
1
7
5
9
337,9
305.2
273.0
306.4
317.8
289.1
340.4
347.2
291.3
304.0
330.7
300.1
324.5
306.4
297.3
256.8
264.0
318.4
251.0
276.4
271.3
312.7
322.5
262.0
327.2
266.1
297.8
280.3
311.4
334.1
304.7
306.0
302.4
316,2
311.0
251.4
283.9
276.7
288.5
284.3
299.8
295.4
316.7
279.8
D-31
-------
Scudy No. 5221.07
SUBCHRQHIC TOXICITY OF META-CRESQL IN SPRAGUg DAWLE? RATS
HALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 4 old 4 new 5 old 5 new 6 old 6
DOSE LEVEL
450 mg/Vg/day
3491
3492
3493
3494
3495
3496
3497
3493
3499
3500
3501
3502
3503
3504
3505
3506
3507
3503
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
491.5
516.5
602.1
510.4
609.1
573.9
463.6
480.3
512.6
477.2
436.2
497.3
507.9
dead
492.6
495.9
522.9
531.7
494.1
467.9
515.2
477.5
426.1
457.0
571.1
561.1
507.7
485.6
476.8
456.4
348.1
347.0
437.9
310.7
409.9
437.7
249.9
306.7
310.3
285.8
332.5
343. 3
345.7
_'
310. S
346.3
325.7
457.8
299.1
262.8
360.7
332.1
422.0
292.4
393.5
435.4
338.4
439.5
343.8
320.6
502.6
478.7
484.6
435.8
4S1.0
469.2
449. S
438.9
4S4.9
439.1
471.3
450.5
486.2
_
450.5
479.3
459.2
457.1
474.9
454.0
455.5
440.7
457.6
452.9
542.9
517.3
466.7
438.4
456.8
455.4
261.4
281.9
323.7
239.0
235.2
316.6
252.3
261.4
293.5
256.5
310.4
301.7
301.7
_
257.7
329.4
260.7
267.8
299.1
272.5
273.7
283.0
276.1
275.6
367.4
373.7-
265.2
234.0
323.8
316.1
471.8
506.8
474.0
461.4
466. 4
482.5
460.3
462.1
471.8
459.0
469.7
476.4
465.1
_
467.8
453.0
464.4
497.1
494.9
439.9
475.5
447.3
477.8
431.4
526.3
506.4
484.5
484.2
450.4
446.0
399.5
440.3
307.4
271.7
298.9
332.3
271.8
293.2
281.9
276.9
303.9
334.3
292.6
_
289.4
300.3
265.7
275.9
337.9
276.0
291.0
285.6
337.1
319.4
373.5
374.7
308.5
324.4
316.7
312.6
D-32
O C;
-------
Study No, 5221.07
SU8CHRON1C TQXtCm OF META-C2ESQL IN SPRftGUE DAUL.EY RATS
KALE FOOT CONSUMPTION DATA (3)
[Feeder Weights]
ANIMAL NO. new 7 old 7 new S old S new 9 old 9
DOSE LEVEL
0 mg/kg/day 3401
3402
3403
3404
3405
3406
3407
3403
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
342S
3429
3430
50 mg/kg/day 3431
3432
3433
3434
3435
3436
3437
3433 •
3439
3440
3441
3442
3443
3444
3445
3446
a Food offered for a
b Food offered for a
477.3
484.2
449,4
492.8
495.9
479.9
529.5
518-8
453.9
452.0
528.9
446.6
458.8
472.4
495.8
459.5
450.4
547.2
47S.4
453.8
499.1
555.2
470.8
596.7
465.6
495.9
484.4
516.6
473.2
480.7
497.1
462.6
529.3
527.8
483.4
435.4
479.0
458.4
493.8
528.0
549.0
496.8
517.8
562.4
537.0
516.7
3-day
4-day
364. 8 b ISAC
,414.3E ISAC
396. 8 a ISAC
395.0^ ISAC
D
393.7 ISAC
418. 8a ISAC
450,83 tSAC
427. 5 b ISAC
364. 9b ISAC
369, OS ISAC
341,0 444.7
2S6.7 448.5
282.0 433.1
288.9 436.7
312.8 434.4
297.8 435.9
257.7 438.7
382.2 434.3
308,2 435.5
317.1 437.7
2S3.2 433.4
315.2 437.5
307.5 433.7
425.0 437.6
305.7 430.1
346.9 438.3
313.9 433.9
354.7 437.7
307.6 435.5
307.7 433.3
417.33 ISAC
381. 8 a ISAC
418. 7fa ISAC
433. 1b ISAC
487. 5b ISAC
414. 13 ISAC
396. 5 a ISAC
356.9» JSAC
421. 9 a ISAC
431, 6 b ISAC
414.1 438.5
332.2 430.8
342.2 440.6
383.3 434.8
375.4 436.5
357.0 438.9
na
na
na
na
na
na
na
na
na
na
289.0
275.8
277.0
263.8
301.5
282.7
261.3
295.9
275.4
313,8
242.4
251.8
274.2
279.8
280.2
306.0
290.2
291.5
287.8
269.2
na
na
na
na
na
na
na
" na
na
na
321.3
268.9
283.2
231.2
296.1
300.3
na
na
na
na
na
na
na
na
na
na
514.9
459.4
458.6
455.8
458.6
445.3
451.4
528.9
445.0
462.3
445.6
508.0
447.3
524.7
463.5
492.4
458.7
445.1
4S9.9
450.7
na
na
na
na
na
na
na
na
na
na
476.9
461.5
468.0
462.6
460.6
463.6
na
na
na
na
na
na
na
na
na
na
293.9
223.6
232.2
242.3
239.4
240.3
217.6
329.3
227.8
295.4
205.3
251.8
243.1
309.4
266.0
335.5
256.2
248.3
290.0
212.0
na
na
na
na
na
na
na
na
na
na
297.7
230.4
267.3
249.2
276.4
273.1
period due to interim sacrifice.
period due to interim sacrifice. 136
B-33 ""
-------
Study No. 5221.07
SUBCHROfJIC TOXICITT OF META-CRESOt IH SPRAGUE DAULEY RATS
HALE FOOD CONSUMPTION DATA (g)
[feeder Weights]
ANIMAL NO. new 7 old 7 new 8 old 3 new 9 old 9
DOSg LEVEL
50 mg/kg/day 3447
(continued) 3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
150 mg/ki/day 3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
34SO
3481
3432
3483
3484
3485
34 £6
3487
3488
3489
3490
491
481
489
541
524
502
484
437
496
482
459
468
494
541
454
474
531
467
550
459
509
493
483
' 526
580
500
503
.0
.2
.0
.2
.0
.1
.1
.6
.1
.5
.1
.9
.7
.2
.1
.7
.7
.7
.6
.7
.9
.9
.6
.2
.1
.9
.2
477.5
485.3
454.3
474.5
457.2
474.2
490.9
458,
491,
.5
.7
516.2
572.4
525.0
504.7
512.1
495.4
502.5
461.2
349
323
299
379
370
306
331
.8
.1
.3
.4
.1
.9
.7
245.2
342
309
308
259
350
368
372
399
437
339
454
389
423
370
426
458
439
340
317
370
.1
.6
.7
.9
.8
.5
aa
.9a
3
.4
.4^
.3a
.2*
-8b
.3a
.3a
.7
.4
.3
.a
327.3
301
.8
2S9.9
284.4
306.7
371.7
290.4
313.0
349.8
404.9
409.9
366.9
398.8
332.3
351,
,4
334.5
435.4
440.3
429.6
451.4
443.9
426.2
425.2
^430. 4
'435.7
438.5
438.1
431.7
433.0
436.8
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
433.6
435.3
439.7
444.3
444.0
437.0
439.9
439.9
437.1
438.2
438.9
437.5
437.3
458.8
439.3
443.4
441.1
439.9
436.2
433.9
307.1
303.8
261 .<$
307.3
299.5
266.8
300.3
255.3
298.6
285.6
299.0
252.9
307.0
277.4
na
na
na
na
na
na
' na
na
na
na
308.4
283.9
2B8.9
297.2
350.5
329.9
279.8
293.9
284.5
352.5
284. 3
269.6
284. S
307.2
321.4
295.8
427.2
267.8
295.7
294.6
457.5
469.7
459.7
464.9
480.2
460.4
476.7
456.1
466.5
470.2
459.1
448.2
461.2
454.0
na
na
na
na
na
na
na
na
r.a
na
474.3
467.7
456.9
456.7
467.9
462.9
470.1
468.6
464.8
460.2
451.1
463.6
441.6
471.3
462.4
460.7
474.3
462.0
464.6
473.0
'2S4.4
290.9
241.6
270.5
285.0
250.3
303.5
271.3
280.1
264.7
265.5
215.5
291.1
281.7
na
na
na
na
na
na
na
na
na
na
287.3
257.7
252.6
261.9
307.3
300.4
257.8
268.2
304.3
232.5
234.7
241.8
237.6
282.3
267.1
288.4
276.7
242.6
261.0
274.1
Food offered for a 3-day period due to interim sacrifice.
Food offered for 'a 4-day period due to interim sacrifice.
D-34
-------
Study No. 5221.07
SUBCHRCH1C TOXICITY OF META-CRESOL IN SPRAGUE OAULEY RATS
HALE FOOD CONSUMPTION DATA (gj
[Feeder Weights]
ANIMAL NO. new 7 old 7 new 8 old 3 new 9 old 9
DOSE LEVEL
450 ing/kg/day 3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
3501
3502
3503
3504
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
, Food offered for
492.3
487.9
591.2
480.3
513.4
566.4
575.6
496.3
497.8
567.4
519.8
558.8
499.4
na
465.9
494.3
467.2
495.7
471.0
524.0
524.6
504.6
481.3
563.1
497.8
570.6
517.6
551.3
553.0
449.6
a 3-day
_ i j
430. 2a
397. 6b
521.63
383.6b
421. 9b
481 .9b
487.4°
4D8.2b
403. 7b
493.0
368.8
423.4
339.9
na
360.5
351.8
376.8
445.0
309.3
311.4
386.1
344.8
360.9
343.4
421.9
388.3
432.4
358.4
393.6
335.5
ISAC
ISAC
'.SAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
ISAC
435.0
440.9
437.3
na
433.2
445.5
444.9
445.0
436.0
438.9
456.6
438.3
437.4
438.6
437.4
433.3
437.3
440.4
443.6
439.0
period due
na
na
na
na
na
na
na
na
na
na
306.3
313.5
292.6
na
278.1
326.9
274.5
264.9
301.9
407.8
278.7
312.3
310.4
312.5
338.9
313.3
305.7
302.7
338.6
321.6
na
na
na
na
na
na
na
na
na
na
465.7
470.6
472.2
na
467.9
467.9
471.3
464.0
472.3
559.3
476.5
473.8
473.5
479.9
478.3
4S4.7
469.7
473.3
499.3
485.1
to interim
^ _ J.^_.UJ
na
na
na
na
na
na
na
na
na
na
267,4
296.0
300.2
na
245.0
298.2
242.7
231.8
274.8
425.5
253.2
286.8
281.8
265.5
260.7
' 302.6
265.7
278.5
350.1
311.5
sacrifice.
Food offered for a 3-day period due to interim sacrifice
D-35
6 -\ H
-^ «j o
-------
Study No. 5221.07
SUBCHRQNIC TQXICITY OF HETA-C8ESOL IN SPRAGUE DAULEY RATS
MALE FOOD CONSUMPTION DATA lg)
[Feeder Weights]
ANIMAL NO. new 10 old 10 new 11 old 11 new 12 old 12 new 13 old 13
DOSE LEVEL
0 rng/kg/day
50 mg/kg/day
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421 .
3422
3423
3424
3425
3426
3427
3428
3429
3430
3431
3432
3433
3434
3435 •
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
na
na
na
ni
na
na
na
na
na
na
465.6
452.7
481.0
472.1
477.3
453.4
453.6
502.8
463.8
491.4
462.9
472.8
475.9
471.5
451.1
487.8
477.3
474.4-
481.6
472.3
na
na
na
na
na
na
na
na
na
na
464.9
463.2
472.4
466.7
503.9
487.8
na
na
na
na
na
na
na
na
na
na
268.9
260.5
290.8
288.5
284.6
284.2
266.2
334.8
279.5
356.4
249.1
252.0
294.9
292.4
284.6
323.5
300.8
318.9
304.6
322.6
na
na
na
na
na
na
na
na
na
na
312.1
274.6
300.4
281.4
320.2
316.1
na
na
na
na
na
na
na
na
na
na
480.0
480.2
474.3
487.3
481.4
485.5
476.0
486.6
477.9
485.9
476.0
488.4
473.5
495.9
482.2
492.8
478 '.7
481.6
483.6
485.9
na
na
na
na
na
na
na
na
na
na
487.1
494.9
493.4
480.3
498.6
488.9
na
na
na
na
na
na
na
na
na
na
279.0
284.7
289.0
303.5
279. 6
286.6
272.1
319.4
277.4
337.0
244.9
263.4
296.7
312.4
304.4
334.9
293.3
307.9
304.1
330.2
na
na
na
na
na
na
na
na
na
na
342.1
• 310.9
355.4
318.5
324.3
337.4
na
na
na
na
na
na
na
na
na
na
493.7
487.2
486.0
490.0
496.9
500.1
496.6
487.0
487.4
483.3
499.3
499.5
489.6
496.8
496.7
490,7
496,9
521.1
491.7
481.8
na
na
na
na
na
na
na
na
na
na
486.4
479.3
495.6
486.0
495.0
497.3
na
na
na
na
na
na
na
na
na
na
299.9
303.2
284.7
306.3
292.4
335.1
296.6
319.6
292.2
341.2
295.3
292.6
314.8
318.9
303.6
326.5
315.9
333.5
306.4
286.7
na
na
na
na
na
na
na
na
na
na
346.8
283.5
347.0
314.0
331.0
344.2
na
na
na
na
na
na
na
na
na
na
487.0
477.5
488.1
437.4
487.0
500.4
490.4
488.2
483.8
4aa.a
489.2
490.3
476.8
490.6
502.6
481.2
486.9
480.6
490.5
484.5
na
na
na
na
na
na
na
na
na
na
486.0
484.4
489.9
496.0
439. 1
487.6
139
na
na
na
na
na
na
na
na
na
• na
339.5
321.4
353.0
328.9
334.3
347,3
3oa.9
349.5
358.1
362.8
324.5
325.6
319.1
336.0
342.0
312.7
323.6
322.1
320.2
309.4
na
na
na
na
na
na
na
na
na
na
359.5
317.2
368.8
356.3
362.1
367.3
D-36
-------
Study No. 5221.07
SUBCH8QN1C TQXieiTY OF META-C8ESQL IN SPRAGUE DAULEY RATS
HALE FOOD CONSUMPTION DATA (g5
[Feeder Weights]
ANIHAL NO, new 10 old 10 new 11 old 11 new 12 old 12 new 13 old 13
DCSE LIVEL
50 mg/kg/day 3447
(continued) 3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
150 mg/kg/day 3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
- 3471 '
3472
3473
3474
3475
' 3476
3477
3478
3479
3480
3481
3482
3483
3484
3485
3486
3487
3488
3489
3490
468.0
500.6
459.1
478.2
486.5
434.7
488.2
459.2
463.3
462.5
465.7
472.8
470.4
449.9
na
na
na
na
na
na
na
na
na
na
' '464.9
424.7
427.9
440.4
437.9
435.9
435.2
442.4
435.4
433.7
434.6
436.6
431.5
447.9
433.8
432.9
433.7
439.7
437.6
434.5
309.5
349.8
275.0
295.4
313.7
260.9
331.4
274.6
300.2
284.0
307.8
273.8
320.8
233.7
na
na
na
na
na
na
na
na
na
na
293.3
243.2
256.5
266.5
243.4
290.8
248.5
257.1
283.1
250.9
251.1
239.2
255.4
291.4
243.2
307.3
242.6
238.8
266.4
266.0
490.2
494.4
486.5
485.5
492.9
481.1
482.4
484.8
496.4
485.6
488.6
480.1
485.1
484.2
na
na
na
na
na
na
na
na
na
na
430.2
482.9
489.1
498.7
496.8
488.4
493.1
482.7
501.5
491.6
490.5
484.6
497.2
494.5
495.4
482.0
492.3
485.6
484.7
439.5
332.1
355.9
302.4
286.3
325.8
299.7
322.7
309.0
329.0
309.1
325.0
292.6
351.2
304.0
na
na
na
na
na
na
na
na
na
na
314.6
307.5
310.0
324.4
300.7
349.5
339.3
308.0
321.0
323.5
307.8
231.9
325.7
318.7
322.7
344.7
324.2
300.5
322.0
324.4
491.6
506.3
478.3
487.3
481.8
485.4
482.4
485.1
472.8
491.7
484.2
475.3
499.2
477.1
na
na
na
na
na
na
na
na
na
na
486.9
489.9
491.9
491.2
496.5
484.9
486.1
490.4
484.1
485.5
437.6
479.6
485.5
493.9
489.2
485.2
488.9
479.4
434.9
493.8
336.5
357.4
397.3
305.9
318.1
303.4
320.5
316.2
307.9
323.4
336.3
287.5
343.3
280.9
na
na
na
na
na
na
na
na
na
na
320.6
319.2
321.6
322.4
302.5
347.5
323.3
32S.8
303.4
319.5
306.3
294.1
318.0
317.5
316.1
320.1
318.3
298.9
297.6
334.9
484.7
486.4
484.4
487.3
507.8
488.1
482.5
482.9
488.9
484.1
498.6
491.0
488.3
484.2
na
na
na
na
na
na
na
na
na
na
481.4
492.8
484.2
497.7
490.2
481.5
487.2
480.4
485.7
477.4
486.0
483.3
487.4
484.2
487.3
484.8
4B5.1
485.8
480.0
490.7
361.8
384.2
351.4
324.8
354.1
316.2
362.8
319.9
345.0
336.0
359.8
316.2
342.9
315.8
na
na
na
na
na
na
na
na
na
na
372.4
341.4
337.0
360.5
352. 6
399.7
372.6
338.6
360.1
357.5
377.7
325.3
333.8
333.4
374.5
409.7
336.3
334.2
351.9
360.4
D-37
140
-------
Study No. 5221.07
SltBCHRCNIC TOXICITY OF HETA-CRESQL IN SPRACUE DAWLEY RATS
HALE FOOO CONSUMPTION DATA
-------
Study No. 5221.07
SUICHRONIC TQXICITY OF HETA-C8ESOL IN SPRAGU6 DAULE
-------
Study No. 5221.07
SU8CHRONIC TOXICITY OF META-CRESOL IN SPRAGUS OAUIET SATS
HALE FOOD CONSUMPTION DATA (S/day)
ANIMAL NO.
1 WEIK 2 WEEK 3 UEEK 4 UEIK 5 WEEK 6 U'EEK 7
DOSE LEVEL
&
50 mg/kg/day ' 3447
(continued) 3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
150 mg/kg/day 3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3471
3472-
3473
3474
3475
3476
3477
3478
3479
3480
3481
3482
3483
3484
3485
34S6
3487
3488
3489
3490
21.5
23.4
44.5
5.5
29.3
15.7
21.3
*
33,6"
2.7
23.3
28.9
25.7
27.0
25.7
24.4
25.8
23.5
28.3
27.7
28.4
27.0
23.8
28.0
24.4
26.2
25.2
24.1
28.8
20.6
30.4
26.5
34.0
27.9
22.5
28.8
27.1
23.3
23.4
24.3
26.5
27.2
29.4
25.9
18.3
24.2
27.6
26.2
26.6
27.9
27.0
28.6
26.1
25.5
24.4
29.9
25.1
27.1
29.6
28.7
27.7
25.6
35.1
28.9
29.7
28,3
25.6
30.1
22.4
30.7
25.9
25.1
30.0
21.2
29.1
26.6
29.1
27.5
28.7
29.6
29.0
25.1
25.9
17.5
25.9
28.8
28.0
27.7
34.2
23.9
27.4
25.0
25.0
26.9
25.8
24.8
25.8
25,8
22.4
27.2
23.7
29.1
28.4
23.1
24.3
22.2
27.0
26.1
28.3
21.0
25.2
18.4
22.0
22.7
22.0
27.5
22.4
18.5
9.2
27.0
27.2
26.3
25.1
25.1
26.9
32.9
26.0
25.5
24.5
27.8
20.7
28.4
20.0
24.2
28.4
26.0
27.2
29.4
25.2
27.1
26.0
26.6
25.0
33.2
24.7
26.7
7.7
40.7
41.1
23.8
23.3
24.2
31.5
7.3
27.5
26.3
19.5
27.5
28.8
27.6
31.3
20.4
27.6,
25.6
27,5
26. S
23.3
27.9
23.5
25.2
26,6
22.9
23.5
28.2
27,4
17.2
30,8
33.7
35.4
29.4
31.7
39.3
30.9
31.5
25.2
21.8
24.4
23.2
35.8
26.6
22.9
18.2
28.1
38.0
41.1
41.5
40.0
32.7
24.3
23.5
33.8
26.1
29.1
42.6
23.5
25.1
32.1
34.2
24:0
29.4
29.8
35.8
36.5
22.3
33.2
26.9
32.6
28.3
31.4
15.2
22.1
24.8
29.4
24.4
17.2
27.2
18.1
19.1
26,1
24.5
20.0
26.0
25.0
24.5
18.4
27.3
21.6
14.3
23.0
20.1
20.4
14.6
17.9
29.7
11.9
22.4
16.3
18.8
15.8
11.9
16.0
16.5
22.7
14.4
16.1
27.6
20.5
21.4
19.2
22.4
21.3
21.2
17.5
23.0
20.2
22.6
27.1
23.1
22.0
27,9
21.8
27.5
22.0
24.7
21.5
29.9
20.6
24.7
27,1
24.9
23.6
19.6
24.1
23.5
28.9
30.8
19.1
22.6
20.1
22.9
26.5
15.2
22.6
21.8
26.4
24.7
23.9
17.0
24.0
25.5
23.8
23.9
16.4 '
19.7
16.2
23.3
21.6
18.1
Invalid food consumption value.
0-40
o
-------
Study No. 5221.07
C TOXIClTt Of HSTA-CRESOl. IN SPRAGUi OAWLEY RATS
HALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
450
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
3S01
3502
3503
3504
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
20. 3
24.3
24.3
25.5
26.7
20.7
24.6
22.7
28.4
24.9
24.6
20.4
2Z;6
dead
26.4
20.0
26.5
27.0
25.0
23.8
25.0
23.3
21.4
19.4
22.4
17.9
22.2
22.6
20.6
19.9
23.3
26.9
29.2
30.4
•30. 8
-"22.1
27.3
26.5
29.1
.28.5
27.1
24.8
27.7
-
31.5
22.0
2.7.9
25.5
26.6
•26.9
26.1
22.5
23.4
'•22.1
24,2
19.9
22.6
.24.5
23.8
19.2
23.7
23.3
21.3
24.2
26.1
20.1
23.6
20.3
26.3
20.4
30.1
19.5
21.6
_
24.6
22.8
29.7
25.6
29.2
27.8
26.4
20.9
19.8
19.8
23.9
21.3
32.2
24.7
22.1
20.0
20.5
24.2
23.5
25.5
28.5
19.5
28.4
24.8
23.9
27. J
22,0
21.4
23.2
_
26.0
21.4
28.2
10.6
27.9
29.3
22.1
20. 3
9.2
23.5
25.4
18.0
24.2
6.6
19.0
19.4
34.5
28.1
23.0
23. 1
28.0
21.8
23.2
25. 4
27.3
26.1
23.0
21.3
26.4
_
27.5
21.4
23.4
27.0
25.1
25.9
26.0
22.. '>
25.9
25.^
25.1
23.6
28.8
29.2
18.3
19.9
10.3
9.5
23.8
27.1
26.S
21.4
27.0
24.1
27.1
26,0
23.0
20.3 .
24.6
_
25.5
21.8
28.4
31.6
22.4
30.6
26.4
23.1
20.1
23.1
21,8
13.8
25.1
22.8
19.1
19.1
20.7
22.6
23.2
24.2
24.1
21.1
22.1
22.0
•23.5
24.8
21.6
19.3
22.8
_
15.1
20.4
13.0
7.2
23.1
30.4
19.8
22.8
17.2
32.1
10.3
26.0
12.2
27.6
22.8
16.3
•* A
D-A1 1 4
-------
Study MQ. 5221.07
SUSCHRONIC TOXICITt OF HETA-CRESOL !H SPRAGUE OAULEY RATS
MAIE FOOD CONSUMPTION DATA (g/day)
AN1HAL NO. WEEK 8 WEEK 9 UEEK 10 WEEK 11 UEEK 12 WEEK 13
DOSE LEVEL
50 mg/kg/day
3401
.3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
341S
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
2431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
na
na
na
na
na
na
na
na
na
na
26.0
28.8
26.0
28.8
22.1
25.5
29.6
23.1
26.7
19.8
31.8
31.0
26.6
26.3
25.0
22.1
24.0
24.4
24.6
27.4
na
na
na
na
na
na
na
na
na
na
19.6
27.0
26.2
25.6
23.4
23.1
na
na
na
na
na
na
na
na
na
na
27.6
29.5
28,3
26.7
27.4
25.7
29.2
24.9
27.2
20.9
30.0
32.0
25.5
26.9
24.7
19.6
25.3
24.5
25.0
29.8
na
na
na
na
na
na
na
ni
na
na
22.4
28.9
25.1
26.7
23.0
23;8
na
na
na
na
na
na
na
na
na
na
28.1
27.5
27.2
26.2
27.5
24.2
26.8
24.0
26.3
19.3
30.5
31,5
25.9
25.6
23.8
23.5 .
25.2
22,2
25.3
21.4
na
na
na
na
na
na
na
na
na
na
21.8
26.9
24.6
26.5
26. 2
24.5'
na
na
na
na
na
na
na
na
na
na
28.7
27.9
26,5
26.3
28.3
28.4
29.1
23.9
28.6
21.3
33.0
32.1
25.3
26.2
25.4
22.6
26.5
24.8
25.6
22.2
na
na
na
na
na
na
na
na
na
na
20.7
26.3
19.7
23.1
24,9
21.6
na
na
na
na
na
na
na
na
na
na
27.7
26.3
28.8
26.2
29.2
23,6
28,6
23.9
27.9
20.3
29.1
29.6
25.0
25.4
27.6
23.5
25.9
26.8
26.5
27.9
na
na
na
na
na
na
na
na
na
na
19.9
28.0
21.2
24.6
23.4
21.9
na
na
na
na
na
na
na
na
na
na
21.1
22.3
19.3
22.6
21.7
21,8
25.9
19.8
18.0
18.0
23.5
23.5
22.5
22.1
22.9
24.1
23.3
22.6
24.3
25.0
na
na
na
na
na
na
na
na
na
na
18.1
23.9
17.3
20.0
18.1
17.2
D-42
145
-------
Study No. 5221.07
SUBCHRCN1C TOX1CITT OF HETA-CRESCL !H SPRAGUE DAWLEY RATS
MALE FOOD CONSUMPTION DATA Cg/day)
ANIMAL NO. WEEK 3 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13
OOSi LEVEL
50 mg/kg/day 3447
(continued) 3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
150 mg/kg/day 3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3471
3472
3473 -
3474
3475
3476
3477
3478
3479
3480
3481
3482
3483
3484
3485
3486
3487
3488
3489
3490
21.4
22.8
28.0
24.0
24.1
26,6
20,8
29.1
22.8
25.5
23.2
29,8
21.0
26.6
na
na
na
na
na
na
na
na
na
na
20.9
25.2
25.1
24.5
15.6
17.9
26.7
24.3
25.4
14,3
25.8
28.0
25.4
25.3
19.7
24.6
2.3
28.7
23.4
23.2
21.6
22.4
27.3
24.3
24.4
26.3
21.7
23.1
23.3
25.7
24.2
29.1
21.3
21.5
na
na
na
na
na
na
na
na
na
na
23.4
26.3
25.5
24.4
20.1
20.3
26.5
25.1
20.1
28.5
27.1
27.7
25.5
23.6
24.4
21.5
24.7
27.4
25.5
24.9
22.6
21.5
26.3
26.1
24.7
24.8
22.4
26.4
23.3
25.5
22.6
28.4
21.4
23.7
na
na
na
na
na
na
na
na
na
na
23.8
25.9
24.5
24.8
27.8
20.7
26.7
26.5
21.8
26.1
26.2
28.2
25.2
22.4
26.5
17.9
27.3
28.7
24.5
24.1
22.6
19.8
26.3
28.5
23.9
25.9
22.8
25.1
23.9
25.2
23.4
26.8
19.1
25.7
na
na
na
na
na
na
08
na
na
na
23.7
25.1
25.6
24.9
28.0
19,8
22.0
25.0
25. a
24.0
26.1
29.0
24.5
25.1
24.7
19.6
24.0
26.4
23.2
23.6
22.2
21.3
11.6
25.9
23.4
26.0
23,1
24.1
23,6
24.0
21.1
26.8
22.3
28.0
na
na
na
na
na
na
na
na
na
na
23.8
24.4
24.3
24.1
27.7
19.6
22.5
23.5
25.8
23.7
25.9
26.5
23.9
25,2
24.7
23.6
24.4
25.8
26.8
22.7
17.6
14.6
19.0
23.2
22.0
24.6
17.1
23.3
20.6
21.2
19.8
25.0
20.8
24.1
na
na
na
na
na
na
na
na
na
na
15.6
21.6
21.0
19.6
19.7
11.7
16.4
20.3
17.9
17.1
15.5
22.6
21.9
21.5
16.1
10.7
21.3
21.7
18.3
18.6
D-43
-------
Study No. 5221.07
SUSCHRQNtC TOXtCm OF META-CRESOl 1M SPRAGUE DAUIEY RATS
HALE FOOD CONSUMPTION DATA (g/day)
ANIMAL HO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13
DOSE LEVEL
450 mg/kg/day
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
3501
3502
3503
3504
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
na
na
na
na
na
na
na
na
na
na
21.5
21.2
24.1
na
26.7
19.8
28.4
30.0
22.4
5.2
29.7
21.0
21.2
21.0
16.4
20. S
21.9
23.0
17.5
19.6
na
na
na
na
na
na
na
na
na
na
24.8
21.8
21.5
na
27.9
21.2
23.6
29.0
24.7
16.7
27.9
23.4
24.0
26.8
27.2
22-8
25.1
24.4
18.7
21.7
na
na
na
na
na
na
na
na
na
na
25.3
22.2
22.8
na
27.5
21.7
30.1
28.3
27.7
24.4
27.6
24.2
25.8
23.1
29.0
21.8
21.8
24.9
20.7
21.0
na
na
na
na
na
na
na
na
na
na
20.9
13.8
24.3
na
24.4
19.9
29.1
26.3
26.9
29.4
21.1
21.9
18.9
33.5
26.2
22.3
24.2
23.5
24,2
20.0
na
na
na
na
na
na
na
na
na
na
23.9
22.1
25.1
na
26.2
20.7
27.0
27.5
27.6
29.0
22.3
21.4
20.5
27.2
27.5
22.7
24.9
24.2
21.1
23.5
na
na
na
na
na
na
na
na
na
ni
16.4
17.3
21,7
na
24.5
14.2
25.6
26.1
21.2
30.0
20.8
20.4
19.4
21.2
22.0
18.6
19.8
21.4
19.2
18.1
D-44
-------
Study No. 5221.07
SUBCHRQNIC TOXICITY OF META-CRESQL IN SPRAGUE 0AVLEY RATS
FEMALE FOOD CONSUMPTION DATA Cg}
[Feeder Weights]
ANIMAL MO. new 1 old 1 new 2 old 2 new 3 old 3
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3531
3532
3533
3534
3535
3536
3537
3538
3539
3540
3541
3542
3543
3544
35*5
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3571
3572
3573
3574
3575
3576
665.1
662, 8
619.8
621.1
579.7
616.5
620.7
627,3
608.6
500.4
657.9
643.3
616.8
571.2
534.0
630.8
631.8
586.8
625.2
621.8
587.8
568,8
586.4
556.8
673.0
595.0
576.2
616.8
627.4
619.9
627.8
616.2
653.2
613.9
662.9
668.7
636.7
611.8
653.6
611.3
630. 2
636.2
615.6
614.3
66Q.4
651.1
528.6 •
539.0
499.3
426.5
460.9
503.4
505.7
505.3
470.0
357.9
543.4
518.7
513.0
455.1
445.5
515.5
513.7
474.7
503.6
486.7
482.3
441.7
444.5
440.7
561.9
464.7
445.8
477.7
510.5
491.1
510.0
506.9
542.3
494.1
530,3
548.6
505.1
487.9
540.7
501.9
496.3
513.8
490.0
499.7
544.6
519.0
574.6
569.4
534.4
539.4
515.7
559.4
548.1
538.7
522.8
427.0
595.0
538.8
559.7
506.6
493.4
564.0
542.5
509.6
544.9
556.1
548.4
496.8
. 482.7
488.2
610.0
536.9
527.5
553.0
567.2
562.3
518.4
, 531.9
557.3
530.3
555.1
575.8
563.7
560.5
565.7
536.3
536.4
534.1
558.5
558.7
591.8
538.0
442.8
448.6
414.1
409.3
402.6
445.6
441.7
410.9
382.8
208.5
469.3
409.8
453.9
395.3
373.9
452.1
430.6
401.8
420.5
421-6
443.8
409.6
374.8
354.1
499.0
403.4
399.1
416.9
454.7
447.9
403.5
418.2
442.9
401.9
412.2
465.9
425.5
444.7
459.9
415.5
4C6.3
413.2
419.5
446.7
411,6
479.7
442.8
448.6
472.1
464.5
471.9
445.6
441,7
471.8
476.9
418.0
469.8
509.5
453.9
481.1
443.7
452.1
430.6
479.8
420.5
500.0
443.8
514.4
488.2
459.5
499.0
468.8
466.5
491.6
454.7
484.1
482.9
538.1
442.9
463.3
498.9
465.9
489.2
500.1
459.9
456,0
464.5
434.3
500.5
467.4
497. S
536.9
304.1
321.0
363.9
321.9
357.1
344.6
306.8
349.2
336.7
200.9
353.3
377.1
350.8
376.8
331.3
337.0
312.0
299.3
297.9
384.3
339.6
38S.9
353.9
342.4
393.7
333.9
345.5
363.5
347.9
374.0
337.5
428.1
403.2
347.7
280.6
359.9
375.2
413.2
375.6
387.0
361.4
388.4
411.2
407.3
411.1
367.8
D-45
•t n O
i 4 o
-------
Study No. 5221.07
SU8CHSONIC TOXJCm OF HiTA-CRESOL IN SPRAGUE DAWLIY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
A«IMAL NO. new 1 old 1 ney 2 old 2 new 3 old 3
DOSE LEVEL
50 mg/kg/day 3577
(continued) 3578
3579
3530
3581
3582
3583
3534
3585
3586
3587
35S8
3589
3590
150 mg/kg/day 3591
3592
3593
3594
3595
3596
3597
3598
3599
. 3600 .
3601
2602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
674.
655.
609.
633.
644.
625.
651.
607.
592.
631.
650,
660.
652.
630.
415.
500.
407.
438.
410.
496.
508.
441.
545.
412.
576.
450.
9
1
3
4
2
9
4
8
9
4
6
0
3
5
2
4
5
1
7
6
2
7
4
9
4
1
469.3
509.
415.
400.
592.
499.
485.
479.
432.
460.
406.
430.
419.
393.
45B.
424.
440.
447.
4
5
8
5
5
5
4
9
3
3
2
5
5
6
7
1
6
560.
538.
480.
503.
498.
512.
547.
480.
475.
520.
512.
535.
529.
557.
299.
363.
274.
306.
307.
370.
38?.
332.
449,
300.
457.
330.
357.
405.
295.
277.
483.
397.
380.
339.
309.
337.
288.
318.
306.
272.
344.
316.
328.
323.
6
4
2
0
4
8
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7
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316
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524
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437
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411.3
401.2
353,1
319.9
268.5
363.5
356.6
268.1
356.4
394.8
276.9
393.5
435.2
416.6
324.9
310.9
275.2
308.1
3S3.3
359.4
412.6
377.4
372.1
288.9
409.5
333.1
343,7
422.1
315.7
342.2
459.0
356.4
394.5
269.7
343.8
357.7
310.9
345.8
374.0
352.1
356.8
329.1
324.5
327.9
D-46
148
-------
Study No. 5221.07
SUBCHROHIC TOXICITY OF META-CSESQL 1H SPftAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 1 old \ new 2 old 2 new 3 old 3
DOSE LEVEL
450 mg/kg/day
3621
3622
3623
3624
3625
3626
3627
3623
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3643
3649
3650
454.7
434.9
491.5
498.5
456.9
436.6
422.2
461.4
506.0
454.2
510.0
437.1
432.9
518.7
445.5
473.0
468.9
456.6
430.3
462.9
441.3
439.8
425.0
518.6
464.7
460.2
433.7
438.3
448.3
455.8
328.9
333.6
392.1
386.5
351.5
345.7
309.4
350.6
413.0
354.4
414.4
313.6
391.2
404.9
336.4
361.0
362.7
352.9
366.3
346.7
354.7
307.4
307.0
430.2
339.9
368.4
307.9
323.1
341.7
341.2
564.3
581.2
506.1
500.3
557.6
474.6
542.9
496.4
557.9
567.4
449.6
547.2
463.2
450.4
533.2
490.3
438.2
512.3
464.4
494.5
533.2
536.1
482.9
492.4
450.3
528.9
428.1
432.6
465.4
429.3
443.0
432.8
390.0
383.5
443.2
363.9
426.3
355.2
449.6
466.2
350.4
433.6
371.9
342.2
421.9
370.2
328.7
409.3
229.0
385.7
435.3
406.3
351.6
408.6
326.6
419.6
302.6
303.0
342.7
304.7
443.6
482.3
42B.6
436.3
443.2
427. Z
426.3
437.3
449.6
466.2
445.9
485.3
412.2
438.9
449.3
454.4
428.4
426.2
439.3
443.2
435.3
429.1
431.8
438.9
424.1
419.6
441.9
438.5
437.5
423.2
319.3
396.0
329.7
325.8
328.7
308.3
315.4
323.6
345.6
373.5
223.2
281.1
304.5
259.5
374.9
340.2
337.2
344.8
334.1
324.0
337.9
287.7
299.8
357.2
319.0
319.9
332.6
326.8
328.4
303.5
-------
Study No. 5221.07
SUBCHRONIC TOX1C1TT OF META-CRESOL IM SPRAGUE DftytEY RATS
FEMALE FOOD CONSUMPTION DATA
-------
Study No. 5221.07
SUSCHRQNIC TOXIC1TY OF HETA-CRESOL 1H SPRAGUE DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (3)
[Feeder Weights]
ANIMAL NO. new 4 old 4 new 5 eld 5 new 6 old 6
DOS! LEVEL
50 ms/kg/day 3577
(continued) 3578
3579
3580
3581
3582
3583
3584
3585
3586
3587
3588
3589
3590
150 mg/kg/day 3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
; 3601 ''"
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
426
437
489
411
194
546
474
434
472
462
.Q
.6
.5
.8
.0
.2
.6
.6
.a
.5
492.6
485,
.9
526.2
4S2.2
430.3
449.6
429.1
443.1
464.3
465.
500.
455.
4
3
6
598.7
444.
'548.
490.
449.
482.
500.
516.
520.
423.
432.
407.
474.
491,
427.
500.
570.
457.
449.
430.
434.
477.
3
5
6
7
1
1
0
S
2
8
8
1
0
2
1
8
3
3
1
7
1
319.2
326.6
354.9
297.0
352.5*
442.7
362.5
294.3
351.4
352.8
375.5
356.5
399.3
331.5
291.2
306.9
283.5
293.0
319.7
325.5
370.3
325.9
477.2
301.7
416.8 '
336.0'
322.1
355.7
372.2
378.2
395.6
280.6
279.2
233.1
334.2
356.2
298.9
360,1
425.6
325.6
308.1
316.4
271.7
328.3
428.2
440
455
423
454
442
428,
.0
.8
.7
.1
.7
.2
437.3
460.8
425.5
476.6
446.5
433.7
432.9
442.8
440.
442.
439.
456.
444.
489.
433.
477.
479,
519.
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458.
506.
459.
471.
478.
436.
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439.
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440.
429.
,1
9
4
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3
2
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4
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2
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1
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4
6
9
2
2
1
4
325
326
298
310
332
343
330
294
345
308
.9
.5
.6
.2
.5
.6
.2
.9
.0
.6
351.0
311.9
304.4
315.9
324.6
332.5
367.0
317.
352.
.1
,0
333.2
383.
331,
382,
,5
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2
371.3
408.2
343.0
358.
408.
343.
354.
372.
323.
302.
319.
323.
377.
0
3
2
3
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5
8
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342.0
346.
336.
341.
334.
336.
300.
324.
1
8
0
1
8
2
3
438
446
443
423
429
438
443,
424,
.4
.0
.9
.9
.4
,0
.4
.7
433.7
433.3
439.3
433.8
423.0
421.5
401.5
414.7
426.7
422.7
421.
425.
435.
423.
454.
456.
427.
409.
421.
443.
421.
427.
429.
40S.
408.
414.
404.
412.
403.
402.
413.
402.
442.
404.
414.
413.
.2
0
,1
1
7
1
7
3
3
5
9
9
2
9
0
4
1
5
8
6
8
7
0
0
5
1
327
329
278
319
329
342
.9
.6
.4
.7
.1
.0
349.7
273
.3
326.3
327.3
312.8
304.0
292.8
309.7
277.9
286.
4
315.9
293.3
297.
304.
323.
317.
346.
339.
305.
230.
316.
341.
299.
308.
314.
226.
292.
2S4.
290.
267.
2EO.
289.
302.
299.
286.
306.
240.
294.
6
6
9
1
1
8
9
3
S
6
7
S
9
a
7
4
9
9
4
4
2
7
9
7
6
7
Invalid weight.
D-49
-------
Study NTo. 5221.07
SUSCHRONIC TOXICITY OF HETA-CRESCL IN SPRAGUE DAULEY RATS
FEMALE FOOO CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 4 old 4 new 5 old 5 new 6 old 6
DOSE LEVEL
450 mg/kg/day
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3643
3649
3650
491.5
516.5
467.1
510.4
511.0
473.9
468.6
480.3
512.6
477.2
486.2
497.8
507.9
469.3
525.5
473.6
460.2
473.6
4S7.5
412.1
436.8
435.8
453.1
462.0
471.4
53n.O
443.3
423.2
474.5
434.7
350.3
403.4
343.7
372.0
380.9
354.3
328.7
349.9
265.6
351.0
365.8
395.3
402.6
334.6
352.3
339.4
333.5
336.2
289.0
292.1
330.1
257.6
313.7
362.6
342.6
403.9
302.9
282.8
334.3
. 301.9
438.6
472.9
429.7
422.4
426.3
414.1
425.3
425.2
506.4
485.8
433.3
426.1
424.4
423.5'
431.8
426.3
430.4
422.9
493.7
418.3
430.7
442.4
433.7
453.9
425.5
429.7
415.5
429.2
432.7
453.7
289.2
335.4
332.9
307.5
292.5
328.0
301.9
326.3
426.1
365.0
346.3
291.6
317.8
343.6
320.0
306.1
291.5
274.4
287.1
307.9
292.4
324.9
318.9
236.9
319.1
266.4
322.4
340.9
2S8.6
274.8
487.3
440.5
442.2
449.1
444.0
448.2
440.6
445.5
468.2
449.7
461.2
424.9
461.2
435.7
465.8
455.6
473.6
473.9
476.0
469.7
487.4
455.4
470.4
457.6
443.6
445.5
459.3
451.2
455.7
445.8
285.2
340.1
265.0
294.0
287.8
306.0
279.1
290.3
316.2
349.0
287.0
280.6
337.6
261.2
290.6
305.4
312.0
306.4
346.4
306.0
344.2
303.2
285.6
334.6
309.1
325.6
325.6
279.8
285.7
323.7
D-50
-------
Study No. 5221.07
SUSCHHCNIC TOXIC IT? OF HETA-CRESQl IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA
-------
Study No. 5221.07
S'JBCHRQMIC TOXIC1TT OF META-CRESQL IH SPRA-GUE OAWIEY RATS
FEMALE rOOO COMSUHPTION DATA (g)
[Feeder Weights!
ANIHAL NO. new 7 old 7 new 8 old 8 new 9 old 9
DOSE LEVEL
50 nig/ks/day 3577
(continued) 3578
3579
3580
3581
3582
3583
3584
3585
3586
3587
3588
3589
3590
150 mg/ki/day 3591
3592
3593
3594
3595
3596
3597
' 3598
3599
3600
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3613
3619
3620
3.
Food offered £or a
461.1
484.3
455.3
420.7
427.1
484.5
442.5
432.1
439.7
459.6
465.8
450.4
460.9
457.7
466.7
491.1
454.4
434.8
491.2
453.7
442.7
483.6
508.9
482.3
448.5'
468.6
428.5
413.9
507.1
518.4
455.6
458.9
475.5
460.1
482.1
460.9
460.1
478.1
469.1
441.0
423.6
430.0
446.9
431.0
3-day
363.7
374.1
302.2
325.1
347.1
396.4
349.6
251.5
318.6
" 355.1
349.7
322.9
337.1
350.6
408. 4a
H
417.3°
389. 1a
351. 2b
436. 4a
402. 2a
39t.3f
D
422.5
464. 03
h
415.9
!33Q.6
347.7
326.9
316.1
390.0
398.7
340.3
337.6
367.3
334.7 -
371.7
344.5
356.8
380.5
371.2
' 343.0-
303.4
335.7
265.4
320.5
period
436.6
427.7
429.2
428.1
423.1
427.6
426.0
427.3
425.8
432.1
430.9
426.9
430.9
428.3
I SAC
I SAC
I SAC
1SAC
I SAC
1SAC
1SAC
1SAC
iSAC
1SAC
447.9
424.7
428.4
420.1
429.3
436.5
420.2
421.3
430.6
429.9
429.4
437.6
426.4
434.2
429.3
425.7
425. 8
429.4
427.4
425.3
348.4
327.6
339.5
345.2
344.9
343.6
351.7
282.1
311.2
336.1
334.8
324.5
319.7
328.9
na
na
na
na
na
na
na
na
na
na
344.6
307.3
324.0
325.8
324.1
329.0
326.6
307.7
330.1
310.0
326.6
326.4
332.3
343.2
344.3
327.5
295.7
342,2
327.1
317.3
462.2
466.0
468.7
452.1
449,9
445.0
443.3
439.9
442.0
474.0
463.6
448.9
468.1
457.8
na
na
na
na
na
na
na
na
na
na
466.5
462.4
443.6
455.1
476.5
458.9
459.3
453.2
442.7
455.1
462.6
461.6
471.6
472.2
474.0
446.8
443.0
447.3
457.1
446.6
337.9
335.8
329.8
338.8
340.7
322.3
325.5
268.9
321.7
348.8
320.4
305.1
327.1
324.9
na
na
na
na
na
na
na
na
na
na
336.3
310.1
303.8
327.8
375.3
318.9
330.9 '
316.1
307.4
352.4
326.8
317.7
342.4
345.1
358.3
321.2
276.4
326.2
301.8
337.8
due to interim sacrifice.
D-52
-------
Study No. 5221.07
SUBCHRQN1C TOXIC1TY OF META-CRESOL 1M 5PRAGUE 0AHIEY RATS
FEMALE FOOO CONSUMPTION DATA CsJ
[Feeder Weights]
ANIMAL NO. new 7 old 7 new S old 8 new 9 old 9
DOSE LiVEL
450 ms/kg/day 3621
3622
3623
3624
3625
3626
3627
3623
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3648
3649
3650
S3
, Food offered for
452.1
478.1
462.4
479.2
467. Z
454.9
415,6
485.4
432.0
472.0
503.1
484.0
411.6
460.2
521.0
426.0
476.2
440.1
465.0
472.1
451.0
461.4
463.4
534.8
472.7
492.3
445.9
479.3
458.9
417.9
402. 6 a ISAC
428, 8 f* ISAC
409.3 ISAC
411. 8 b ISAC
423. 2 a ISAC
402. 4 b ISAC
359. 7 b !SAC
436.7 a ISAC
371.1 t> ISAC
440
411
376
335
352
443
336
382
334
353
391
367
.3 a ISAC
.8
.6
.9
.4
.5
.8
.8
.7
.3
.1
.4
330.0
352
i49
365
387
353
372
352
313
.5
.3
.4
.8
.4
.0
.7
.1
428
421
427
.7
.4
.5
426.7
434
420
423
425
424
427
425
.6
.6
.4
.7
.6
.0
.7
428.1
421
428
423
.8
.4
.4
425.3
421
436
.S
.1
423.2
429
a 3-day period
.5
due
3.. ~
na
na
na
na
na
na
na
na
na
na
346.
328.
341.
323.
353.
0
2
8
5
9
330.1
328.
325.
328.
332.
343.
311.
313.
355.
320.
327.
313.
319.
307.
330.
to
t. _
6
9
6
B
6
4
7
7
9
a
5 ,
4
1
5
461
461
455
453
487
457
451
455
453
458
na
Hi
na
na
na
na
na *
na
na
na
.2
.3
.1
.3
.9
.9
.6
.4
.4
.3
452.2
470
457
464
441
451
464
469
461
450
.1
.5
.5
.1
.9
.1
.7
.7
.7
later im
332
332
350
322
372
346
321
303
320
337
341
312
324
360
295
. 348
319
326
310
354
na
na
na
na
na
na
na
na
na
na
.5
.5
•.2
.2
.3
.4
.9
.0
.1
.1
,0
,1
.3
.7
.7
.5,
.8 •
.6
.2
.0
sacrifice.
Food offered for a 4-day period due to interim sacrifice
D-53
156
-------
Study No. 5221.07
SU8CHRQH1C TOXICtTY OF HETA-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (i)
[Feeder Weights]
ANIMAL MO. new 10 old 10 new 11 old 11 new 12 old 12 new 13 old 13
DOSE LEVEL
0 n»i/kf/day
50 mg/kg/day
3531
3532
3533
3534
3535
3536
3537
3538
3539
3540
3541
3542
3543
3544
3545
3546
3547 '
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3561
3562
3563
3564
3565
3566
3567
3563
3569
3570
3571
3572
3573
3574 '
3575
3576
na
na
na
na
na
na
na
na
na
na
422.5
437,9
431.6
439.9
424.5
426.9
429.8
422.2
426.8
424.8
423.5
425.7
425.4
423.3
430.6
422.2
447.2
' 440.8
464.4
457.0
na
na
na
na
na
na
na
na
na
na
460.9
435.4
444.6
426.3
461.6
460.5
na
na
na
na
ni
na
na
na
na
na
301.0
315.1
'322.7
346.2
316.9
319.6
303.6
304.7
304.3
318.7
314.9
308.7
297.1
299.2
330.7
296.0
331.8
328.6
373.1
355.0
na
na
na
na
na
na
na
na
na
na
209.2
320.0
325.8
306.2
348.9
336.3
na
na
na
na
na
na
na
na
na
na
444.4
448.7
443.0
455.3
443.5
449.2
441.4
445.5
454.2
436.9
447.6
442.6
442.3
446.5
451.1
445.9
450.4
442.2
444.6
446.4
na
na
na
na
na
na
na
na
na
na
485.1
442.8
449.0
441.9
448.5
448.2
na
- na
na
na
na
na
na
na
na
na
332.2
338.2
339.0
357.1
338.2
332.7
337.4
329.7
339.6
328.8
334.3
324.1
323.0
328.9
345,3
326.2
340.5
336.3
360.6
338.7
na
na
na
na
na
na
na
na
na
na
326.8
341.0
326.3
328.6
330.0
321.8
na
na
na
na
na
na
na
na
na
na
449.7
460.7
445.2
451.3
441.0
450.0
450.0
445.7
444.4
448.2
447.0
452.3
443.3
465.2
448.8
446.6
446.0
443.2
451.0
443,8
na
na
na
na
na
na
na
na
na
na
444.6
453. B
449.2
454.2
445.8
453.9
na
na
na
na
na
na
na
na
na
na
316.1
345.2
339.8
349.0
347.2
347.3
318.0
325.3
323.5
333.3
329.9
320.7
310.6
348.4
334.1
318.6
334.3
322.6
347.7
329.6
na
na
na
na
na
na
na
na
na
.na
318.3
341.7
309.7
335.5
319.7
321.7
na
na
na
na
na
na
na
na
na
na
447.2
447.1
447.2
449.4
451.9
459.7
446.0
454.2
451.2
456.0
471.0
443.7
443.4
445.8
443.6
457.3
453.6
447.1
465.8
446.9
na
na
na
na
na
na
na
na
na
na
446.4
452.8
451.5
451.5
446.9
444.3
na
na
na
na
na
na
na
na
na
na
355. 7
374.5
361.4
363.6
344.1
364.5
322.9
344.4
352. 1
365.0
371.3
329.6
325.3
343.6
340.8
367.2
349.7
349.6
372,7
346.7
na
na
na
na
na
na
na
na
na
na
344.5
356.6
339.6
365.2
352.9
364.9
D-54
L 0 f
-------
Study No. 5221.07
SUaCHRONIC TOXIC1TY OF HETA-CRESOL IN SPRAGUE OAWLEY RATS
FEMALE FOOD CONSUMPTION DATA
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF HETA-CRESOL IN SPRAGUE DAULEY RATS
FEMALE FOOO CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 10 old 10 new 11 old 11 new 12 old 12 new 13 old 13
DOSE LEVEL
450 mg/kg/day
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3648
3649
3650
na
na
na
na
na
na
na
na
na
na
431.7
450.5
422.8
420.8
467.2
443.3
420.4
420.8
420.6
452.9
418.9
449.2
448.7
464.6
430.7
458.9
425.7
452.9
445.4
432.1
na
na
na
na
na
na
na
na
na
na
339.1
326.5
341.9
311.8
356.9
329.0
314.5
286.9
307.0
336.4
325.8
311.1
325.2
372.8
296.5
336. V
303.1
326.0
318.9
326.4
na
na
na
na
na
na
na
na
na
na
443.9
444.4
448.1
442.2
442.3
447.4
449.3
442.5
444.3
440.5
442.0
442.9
445.4
448.1
443.3
444.6
444.0
459.8
446^5
446.6
na
na
na
na
na
na
na
na
na
na
355.9
326.7
356.4
326.9
334.8
342.0
344.1
325.8
333.0
333.6
362.4
312.9
329.5
356.3
317.4
332.3
318.7
332.2
315.3
308.5
na
na
na
na
na
na
na
na
na
na
473.9
462.8
455.8
451.4
467.7
447.1
444.8
454.0
444.5
449.9
447.5
446.8
452.7
449.4
447.7
446.8
447.5
461.3
451.9
440.2
na
na
na
na
na
na
na
na
na
na
366.3
324.1
351.9
344.9
352.9
315.4
332.2
333.0
317.5
317.1
358.0
312.4
349.1
347.6
319.4
342.8
315.9
337.1
318.0
318.0
na
na
na
na
na
na
na
na
na
na
444.8
452.6
444.1
447.1
457.4
445.8
452.1
443.4
445.7
452.4
463.0
448.9
467.4
45?. 8
444.6
444.5
445.4
469.8
451.4
443.4
na
na
na
na
na
na
na
na
na
na
349.5
353.9
369.7
353.4
377.3
339.4
369.4
360.2
354.8
358.4
380.5
317.6
376.3
391.5
339.6
341.7
356.9
356.3
361.8
339.8
D-56
159
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IM SPRAGUE OAWLiY RATS
FEMALE FOOD CONSUMPTION DATA Cg/day)
ANIMAL NO. WEEK 1 UEEK 2 WEEK 3 UEE1C 4 UEEK 5 UEE1C 6 y£EK 7
DOSE LEVEL
0 mg/ki/day
50 mg/kg/day
3531
3532
3533
3534
3535
3536
3537
353S
3539
3540
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3553
3559
3560
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3571
3572
3573
3574
3575
3576
19.5
17.7
17.2
19.2
17.0
16.2
16.4
17.4
19.8
20.4
16.4
17.8
14.8
16.6
19.8
16.5
16.9
16.0
17.4
19.3
15.1
18.2
20.3
16.6
15.9
18.6
18.6
19.9
16.7
18.4
16.8
15.6
15.8
17.1
18.9
17.2
18.8
17.7
16.1
15.6
19.1
17.5
17.9
16,4
16.5
18.9
18.3
17.3
17.2
18.6
16.2
16.3
15.2
18.3
20.0
31.2
17.9
18.4
15.1
15.9
17,1
16.0
16.0
15.4
17.8
19.2
14.9
12.5
15.4
19.2.
15.9
19.1
18.3
19.4
16.1
16.3
16.4
16.2
16.3
18.4
20.4
15.7
19.7
16.5
15.1
17.3
18.6
17.3
19.9
16.0
25.7
8.3
19.8
18.2
15.5
20.4
16.4
14.4
19.3
17.5
20.0
31.0
16.6
18.9
14.7
14.9
16.1
16.4
16.9
25.7
17.5
16.5
14.9
18.4
19.2
16.7
15.0
19.3
17.3
18.3
15.3
15.7
20.8
15.7
5.7
16,5
31.2
15,1
16.3
12.4
12.0
9.9
14.7
13.7
12.8
8.6
12.3
24. Z
19.1
16.6
14.1
18.3
18.5
14.0
11.4
17.9
17.2
24.0
17.3
13.0
15.9
16.5
16.9
2.7
18.1
17.6
17.2
18.8
16.6
17.4
20.3
16.4
16.1
19.1
17.5
17.5
15.1
17.3
20.3
20.3
17.6
18.7
23.3
19.6
24.4
20.3
21.1
20.6
23.9
24.2
27.4
24.2
25.5
18.6
19.5
16.5
13.8
18.2
14.6
12.5
14.3
18.1
20.7
18.7
19.0
16.3
14.1
20.1
14.9
14.7
17.0
17.4
12,1
16.1
17.6
18.0
15.8
17.2
15.9
16.5
17.6
17.7
13.1
16.6
16.2
17.1
16. S
18.3
15.2
17.1
18.4
15.5
16.3
16.2
25.7
18.2
18.8
15.4
16.9
17.2
20.6
16.6
14.1
18.8
16.6
15.1
14.8
17.1
17.7
21.7
18.5
17.6
15.5
15.6
16.3
18.0
17.2
18.5
18.6
16.4
16,9
16.7
18.0
16.4
15.0
16.6
18.9
18.1
13.9
H.9
16.0
17.1
14.4
17.0
12.7
16.9
17.6
16.0
15.6
14.6
15.8
14.9
16.6
16.0
14.1
17.2
28.0
10.4
21.8
10.0
16,8,
15.3
28.7
2.9
19.5
19.4
16.3
19.1
14.8
13.7
14.5
16.7
16.4
17.1
16.3
15.6
14.1
15.4
18.0
16.3
13.0
15.8
17.3
16.1
11.9
13.9
15.3
16.8
16.5
12.9
20.1
17.5
17.2
16.8
17,0
64.9
17.9
17.3
17.1
14.2
16.4
18.4
D-57
-------
Study No. 5221,07
SU8CHRON1C TOXIC!?! Of META-CRESOL IN SfftAGUE DAULEY RATS
FEMALE FCGO CONSUMPTION DATA Cg/day)
AN1HAL HO. WEEK 1 WEEK 2 USEK 3 WEEK 4 WEEK 5 KEEK 6 UEEK 7
50 mg/kg/clay " 3577
(continued) " 3578
3579
3580
3S81
3582
3583
3534
3585
3586
3587
3588
3S89
3590
150 Big/kg/day 3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
16.3
16.7
18.4
13.6
20.3
16.2
14. 8
18.2
16.8
15.8
19.7
17.8
17.5
10.5
16.6
19.6
19.0
18.8
14.3
18.0
17.6
15.6
13.6
16.1
17.1
17.0
16.0
14.8
17.1
17.6
15.6
14,5
15.0
20.0
17.7
17.5
16. a
16.0
16.1
17.2
16.3
15.5
16.0
17.8
21.2
15.2
18.4
18.0
36.1
14.9
17.9
20.3
13.0
15.0
18.5
17.5
20.5
16.9
16.6
19.1
17.4
19.5
16.8
19.4
16.3
16.4
14.8
17.3
17.5
19.0
18.0
14.3
17.7
16.9
14.4
19.0
16.0
16.8
13.1
17.0
16.6
15. 0
14.3
17.1
16.7
14.9
16.0
18.4
6.9
a. 4
19.3
15,9
32.0
14.4
15.2
22.9
17.2
18.3
31.8
18.6
17.5
15.5
17.3
20.9
13.5
18,4
15.6
18.4
15.0
16,6
14.6
18.3
17.5
18.0
14,3
14.5
17.4
18.5
15.4
15.0
6,1
28.8
17.9
16.9
17.6
15.7
14.6
17.2
16.0
14.2
18.1
16.2
15.3
15.9
19.2
16.4
*
14.8
16.0
20.0
17.3
15.7
16.7
18.5
18.1
17.2
19.9
20.4
20.8
21.4
20.7
20.0
18.6
18.5
17.4
20.4
18.8
22.1
18.2
18.1
18.3
19.7
17.9
20.4
21.9
25.0
20.0
19.3
18.3
20.0
20.7
13.8
20.2
16.2
23.3
21.3
14.6
16.2
22.5
16.2
17.4
14.2
14.0
20.3
16.5
16.7
17.9
19.2
18.5
16.7
16.9
15.4
10.8
17.5
14.9
IS .9
15.2
14.6
13.6
15.4
15.9
16.9
14.3
14.1
16.6
16.7
15.1
' 16.1
15.6 '
17.8
15.1
16.0
13.4
13.9
12.7
14.1
16.6
13,5
20.0
15.0
15.8
16.6
23.6
14.9
14.3
13.7
13.4
21.6
15.3
15.1
18.1
18.5
18.6
16.0
17.7
18.3
15.8
18.5
17.7
17.2
15.9
15.1
15.5
16.6
17.4
18.4
14.9
14.6
17.5
17.0
16.3
17.4
16.5
18.6
16.2
20.7
17.6
16.2
15.9
14.7
22.2
13.9
22.0
16.9
13.9
15.6
21.9
13.7
11.4
12.6
13.3
25.8
17,3
14.9
16.6
18.2
17.7
15.3
19.4
18.5
21.8
20.9
18.3
17.2
17.1
15.3
15.0
16.6
16.8
17.3
14.5
14.0
16.7
17.1
16.5
17.3
15.4
17,9
15.8
16.6
14.3
13.9
14.0
14.0
17.9
13.5
25.9
15.3
* Invalid food consumption value.
.D-58
16
-------
Study No. 5221.07
SUBCHRCMIC TOXICITY OF META-CHESOL IN SPRAGUE DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
450 mgAg/day
3621
3622
3623
3624
3625
3626
3627
362S
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3643
3649
3650
18.0
14.5
14.2
1610
15.1
13.0
16.1
15.8
13.3
14.3
13.7
17.6
13.1
16.3
15.6
. 16.0
15.2
14.8
16.3
16.6
12.4
18.9
16.9
12.6
17.3
13.1
18.7
15.7
15.3
16.4
17.3
14.1
16.6
16.7
16.3
15.1
16.7
20.2
15.5
14.5
14.2
16.2
13.0
15.5
15.9
17.2
15.6
14.8
33.6
15.5
14.0
1B.5
18.8
12.0
17.7
15.6
17.9
18.5
17.5
17.8
17.8
12.4
14.1
15.9
16.4
17.0
15.8
16.3
14.9
13.2
31.1
29.2
15.4
25.6
10.7
16.3
13.0
11.6
15.0
17.0
13.9
20.2
18.9
11.7
15. a
14.2
15.6
16.0
15.6
17.1
20.2
16.2
17.6
19.8
18.6
17.1
20.0
18.6
35.3
18.0
17.2
14.6
15.0
19.2
24.7
19.2
18.1
19.6
28.4
17.1
15.2
25.5
19.2
14.2
18.4
18.0
20,1
20.1
20.0
19.0
21.3
19.6
13.8
16.4
19.1
12.3
17.6
14.1
11.5
17.3
12.4
19.2
15.2
11.4
16.0
17.2
19.8
21.2
29.5
15.8
19.8
16.8
16.4
31.0
15.2
23.3
13.3
12.6
20.6
25.6
28.9
14.3
25.3
22.2
22.3
20.3
23.1
22.2
21.7
14.4
24.9
20.6
17.7
24.9
25.0
21.5
23.1
23.9
18.5
23.4
20.5
21.7
26.4
17.6
19.9
17.1
19.1
24.5
24.3
17.4
16.5
16.4
13.3
16.8
14.7
13.1
14.0
16.2
15.2
10.6
13.0
15.3
10.8
15.4
11.1
12.7
13.3
15.1
16.0
11.6
11.9
18.8
15.8
12.2
15.3
15.0
13.2
15.4
15.2
14.3
D_59
-------
Study No. 5221,07
SUBCHROHIC TOXICITT OF HETA-CRESOL IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA
-------
Study No. 5221.O/
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA Cg/day)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13
DOSE LEVEL
50 mg/kg/day 3577
(continued) 3578
3579
3580
3581
3582
3583
3584
3535
3586
3587
3538
3589
3590
150 mgAg/day 3591
3592
3593
3594
3595
3596
3597
3593
3599
3600
3601
3602
3603
3604
3605
3606
3607
3603
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
14.7
16.7
15.0
13.8
13,0
14.0
12.4
24.2
19.1
16.0
16.0
17.1
18.5
16.6
na
na
na
na
na
na
na
na
na
na
17.2
19.6
17.4
15.7
17.5
17.9
15.6
18.9
16,8
20.0
17.1
18.5
15.7
15.2
14.2
16.4
21.7
U.5
16.7
18.0
15.5
16.3
17.4
14.2
13.7
15.3
14.7
21.4
15.0
15.7
17.9
ia.o
17.6
16.6
na
na
na
na
na
na
na
na
na
na
' 16.3
19.0
16.9
15.9
12.7
17.5
16.1
17.1
16.9
12.3
17.0
18.0
16.2
15.9
14.5
15.7
20.8
15.1
19.4
13.6
18.2
16.9
15.4
13.6
13.3
13.1
13.0
21.2
16.6
15.4
17.5
18.9
16.8
15.2
na
na
na
na
na
na
na
na
na
na
18.2
20.5
16.3
14.6
7.7
17.8
16.4
18.5
15.1
8.4
17.0
17.9
16.1
15.7
15.8
16.0
20.1
15.4
20.2
7.9
14.7
15.7
17.5
13.1
13.9
13.4
13.3
17.8
17.1
16.2
15.4
17.9
18.5
14.7
na
na
na
na
na
na
na
na
na
na
18.2
21.3
18.3
17.2
20.8
19.5
17.0
18.3
16.9
23.2
17.2
13.4
17.2
14.8
17.2
15.7
22.0
15.1
15.7
20.5
14.9
17.3
17.6
13.8
14.9
15.1
14.6
19.7
18.0
17.0
16.3
19.7
19.9
15.6
na
na
na
na
na
na
na
na
na
na
17.8
22.1
15.4
18.0
18.5
17.4
16.0
19.9
18.9
20.2
16.4
18.3
13.3
17.6
15.5
15.5
22.3
14.3
14.9
21.8
11.6
13.7
16.0
11.7
12.0
12.0
12.3
16.4
15.7
12.7
14.0
15.9
16.6
11.2
na
na
na
na
na
na
na
na
na
na
15.2
16.9
11.9
15.4
11.7
14.1
11.9
13.9
15.7
14.1
14.5
16.0
15.0
15.8
12.0
12.5
19.6
12.2
13.5
14.0
D-61
164
-------
Study No. 5221.07
SUBCHRON1C TOXICITY Of META-CRESCl IM SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 UEEK 12 WEEK 13
DOSE LEVEL
450 mg/kg/day
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3648
3649
3650
na
na
na
na
na
na
na
na
na
na
13.3
15.5
14.3
17.2
13.5
15.1
15.8
16.6
16.0
15.7
13.7
19.5
18.0
12.1
17.1
16.3
18.1
19.5
19.3
16.5
na
na
na
na
na
na
na
na
na
na
16.1
16.1
13.1
16.4
14.4
13.9
16.2
19.1
16.7
15.2
13.9
19.3
16.7
13.0
IB. 2
12.9
18.0
17.9
18.9
12.1
na
na
na
na
na
na
na
na
na
na
13.2
17.7
11.6
15.6
15. 3
16.3
15.1
19.1
16.2
16.6
13.3
19.7
17.6
13.1
19.2
17. 4
17.5
18.1
18.1
15.1
na
na
na
na
na
na
na
na
na
na
13.3
16.8
13.1
16.5
15.4
15.1
15.0
16.7
15.9
15.3
11.4
18.6
16.6
13.1
18.0
16.0
17.9
18.2
18.7
19.7
na
na
na
na
-. na
na
na
na
na
na
15.4
19.8
14.8
15.2
16.4
18.8
16.1
17.3
18.1
19.0
12.8
19.2
14.8
14.5
18.3
14.9
18.8
17.7
19.1
17.5
na
na
na
na
na
na
na
na
na
na
13.6
14.1
10.6
13.4
11.4
15.2
11.8
11.9
13.0
13.4
11.8
18.8
13.0
9.6
15.0
14.7
12.6
16.2
12.8
14.8
D-62
•* f* •*•'
.100
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE DAWLEY RATS
MALE HEMATOI.OGT VALUES
[Interim Sacrifice!
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
ANIMAL KG.
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3431
3432
3433
3434
3435
3436
3437
343S
3439
3440
3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
RBC
(x 10*6/17171*3)
7.32
8.33
7.99
7.90
• 7.46
8.15
8.02
8.11
8.68
3.43
7.88
7.35
7.73
7.43
8.58
7.04
8.43
7.38
7.60
7.68
7.74
7.68
7.42
7.48
7.29
3.43
7.29
7.89
7.39
8.21
7.77
7.41
7.64
7.42
7.17
7.65
7.58
7.96
7.42
8.47
HCB
(g/di)
14.7
15.2
15.1
14.9
14.8
15.3
15.6
15.6
15.4
16.1
16.0
15.3
15.7
14.8
15.8
14.3
15.8
14.8
14.3
15.4
14.6
14.9
15.3
14.6
15.0
16.1
14.7
15.4
14.8
16.3
14.5
15.2
15.0
15.0
14.8
14.2
15.0
15.6
15.3
16.1
HCT
39.9
42.5
42.6
42.1
41.9
42.0
41.6
42.6
44.0
44.7
43.4
39.9
43.5
39.2
44.8
38-9
44.7
39-8
39.5
42.2
38.9
40.4
40.2
40.9
41.7
44.2
40.5
43.1
40.9
46.0
41.4
42.3
40.9
40.5
39.9
39.6
40.6
43.1
39.2
44.6
PT
(see.)
13.0
13.6
11.6
12.5
13.3
13.1
13.1
13.1
11.5
11.9
12.2
12.5
12.4
13.4
12.5
12.5
10.7
11.9
11.6
11.5
13.4
12.8
10.4
13.3
12.0
14.8
11.9
10.8
10.7
12.9
11.6
12.8
11.7
10.7
10.5
12.9
11.2
10.7
10.7
11.7
APTT
(sec.)
30.6
36.8
35.1
33.9
31.9
35.6
34.3
32.0
30.8
35.6
34.7
33.0
32.8
34.6
33.4
34.9
10.8
30.8
36.3
31.8
33.9
32.0
32.3
32.9
31.4
37.8
35.8
40.4
30.6
30.9
35.9
33.0
31.1
30.4
35.9
34.1
31.1
29.7
34.0
34.6
RET 1C
(X rbc)
0.1
2.1
1.2
0.4
0.7
0.8
1.3
0.1
0.4
1.1
2.4
1.0
1.1
0.1
0.3
2.1
1.3
1.0
0.3
1.1
1.6
0.8
0.3
0.7
0.7
0.9
1.5
0.8
2.0
1.6
0.6
0.8
0.8
1.8
0.1
0.1
1.0
0.6
0.1
0.6
D-63
L66
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE OAULEY RATS
MALE HEHATOLOGY VALUES
[Interim Sacrifice]
DOSE LEVEL
0 mg/kg/day
AHIHAL NO. WBC SEGS BANDS LYMPHS MONO EOS
(x 10*3/imA3) (X UBC) (.% UBC) <* UBC) (X UBC) (X WBC)
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
3401
3402
3403
3404
3405
3406
3407
3403
3409
3410
3431
3432
3433
3434
3435
3436
3437
3433
3439
3440
3461
3462
3463
3464
3465
3466
3467
3463
3469
3470
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
8.7
12.9
11.0
17.5
11.2
15.1
12.2
13.3
15.6
17.1
11.4
14.9
11.7
17.8
20.3
12.4
10.1
16.6
3.9
16.5
15.9
9.2
12.8
12.6
14.0
9.7
9.8
13.1
8.1
14.1
8.1
11.1
14.9
13.0
13.6
13.8
14.5
18.4
12.2
15.2
27
33
20
25
12
11
5
21
7
8
20
20
18
24
2°
3
25
50
25
32
31
20
13
23
15
9
17
10
12
32
19
28
22
20
5
20
19
26
16
22
1
0
0
0
0
0
0
1
0
0
0
0
0
0
1
2
0
0
0
0
1
1
0
1
0
0
0
0
3
0
0
0
0
0
0
0
0
0
2
0
72
65
79
75
85
89
94
74
93
89
73
75
80
75
76
91
71
49
75
65
66
79
86
75
84
a?
82
88
84
68
79
69
77
78
94
76
81
72
80
75
0
1
1
0
2
0
1
3
0
3
3
2
1
0
2
3
1
0
0
1
0
0
0
1
0
1
1
1
0
0
1
3
1
2
1
3
0
0
1
2
0
1
0
0
0
0
0
1
0
0
4
3
1
1
1
1
3
1
0
2
0
0
1
0
1
1
0
1
1
0
1
0
0
0
0
1
0
2
1
1
D-64
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE OAWLEY RATS
HALE HEHATOLOGY VALUES
[Interim Sacrifice]
ANIMAL NO.
WBC
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
(x
SEGS BANDS LYMPHS
(x 10*3/nro*3) (x 10"3/imT3) (x 10*3/rmT3) (x
MONO
EOS
(x
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3461
3462
3463
3464
3465
3466 '
3467
3468
3469
3470
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
8.7
12.9
11.0
17.5
11.2
15.1
12.2
13.8
15.6
17.1
11.4
14.9
11.7
17.8
20.3
12.4
10.1
16.6
8.9
16.5
15.9
9.2
12.8
12.6
14.0
9.7
9.8
13.1
8.1
14.1
8.1
11.1 '
14.9
13.0
13.6
13.8
14.5
18.4
12.2
15.2
2.3
4.3
2.2
4.4
1.3
1.7
0.6
2.9
1.1
1.4
2.3
3.0
2.1
4.3
4.1
0.4
2.5
8.3
2.2
5.3
4.9
1.8
1.7
2.9
2.1
0.9
1.7
1.3
1.0
4.5
1.5
3.1
3.3
2.6
0.7
2.8
2.8
4.8
2.0
3.3
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.2
0.0
0.0
0.0
0.0
0.2
0.1
0.0
0.1
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
6.3
8.4
8.7
13.1
9.5
13.4
11.5
10.2
14.5
15.2
8.3
11.2
9.4
13.4
15.4
11.3
7.2
8.1
6.7
10.7
10.5
7.3
11.0
9.5
11.8
8.6
8.0
11.5
6.8
9.6
6.4
7.7
11.5
10.1
12.8
10.5
11.7
13.2
9.8
11.4
0.0
0.1
0.1
0.0
0.2
0.0
0.1
0.4
0.0
0.5
0.3
0.3
0.1
0.0
0.4
0.4
0.1
0.0
0.0
0.2
0.0
0.0
0.0
0.1
0.0
0.1
0.1
0.1
0.0
0.0
0.1
0.3
0.1
0.3
0.1
0.4
0.0
0.0
0.1
0.3
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.5
0.4
0.1
0.2
0.2
0.1
0.3
0.2
0.0
0.3
0.0
0.0
0.1
0.0
0.1
Q.1
0.0
0.1
0.1
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.4
0.1
0.2
1.68
D-65
-------
Study HO,
SUBCHROtUC TOX1CITY OF HETA-CRESOL IN SPRAGUE DAULEY RATS
MALE HEKATOLOGY VALUES
[Terminal Sacrifiee!
5221,07
DOSE LEVEL
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
ANIMAL HO.
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3441
3442
3443
3444
3445
3446
3447
3448
3449
3450
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3501
3502
3503
3505
3506
3507
3508
3509
3510
3519
R6C
(x 10*6/irro"3
9.59
8.83
8.71
8.90
8.29
8.74
8.90
9.02
8.97
9.14
8.25
8.71
8.68
9.15
9.02
8.69
8.77
8.83
8.44
8.43
9.29
9.18
8.42
8.71
na
9.72
8.75
8.53
9.60
9.dO
8. SB
8.57
8.60
8.89
8.60
8.89
8.77
9.11
7.88
8.51
HGB
5 (g/dl)
15.6
16.3
15.8
16.0
14.7
15.3
15.8
15.3
16,4
16.0
14.9
14.8
15.6
16.1
15.9
15.1
15.4
15.9
15.3
15.5
16.7
16.9
15.3
15.9
.17.3
17.0
15.8
16.4
16.1
16.4
15.2
15.7
15.4
16.3
15.6
16.4
15.7
15.5
15.0
16.4
HCT
C%>
44.5
44.5
45.0
45.0
41.2
43.4
42.9
43.5
45.0
44.2
41.7
41.2
43.4
44.5
45. S
41.7
43.7
44.4
42.3
41.9
46.1
48.6
45.3
45.2
49.0
46.6
44.2
46.0
43.7
45.4
42.8
43.5
44.8
46.7
43.3
46.6
43.5
43.9
42.8
46.2
PT
(sec.)
7.5
11.5
12.9
10.9
11.3
11.5
12.9
12.7
12.2
9.5
11.4
6.7
12.7
13.6
11.7
12.8
12.4
8.1
13.0
11.3
10.2
11.9
12.0
11.8
12.5
12.2
12.3
12.3
16.6
10.5
13.3
13.3
11.4
11.4
12.4
11.7
13.4
12.9
10.9
9.0
APTT
(sec.)
14.0
33.6
35.6
33.5
32,7
33.9
38.8
35.4
34.3
35.0
34.4
35.5
35.1
35.2
36.2
37.1
30.8
36.1
33.7
33,8
37.4
34.5
39.2
34.6
36.1
27.9
35.5
33.1
39.8
41.5
37.2
23,4
36.6
33.3
34.4
36.9
43.3
38.5
33.9
41.5
RET1C
(% rbc)
0.9
0.8
0.9
0.6
1.1
0.9
0.3
1.1
0.7
0.4
1.1
0.2
0.5
o.a
0.2
0.8
0.3
0.8
0.4
0.7
0.6
0.2
0.5
0.3
1.6
0.3
0.3
0.6
1.4
0.3
0.5
0.2
0.8
1.9
1.3
0.3
0.8
1.4
0.6
0.1
D-66
169
-------
Study No, 5221.07
SUBCHRONIC TCXtCm OF META-CRESOL IN SPRACUE DAWLEY RATS
HALE HEMATOLOGY VALUES
[Terrainal Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mgAg/day
150 mg/kg/day
450 mg/kg/day
ANIMAL HO.
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3441
3442
3443
3444
3445
3446
3447
3448
3449
3450
3471
3472
3473
3474
3475
3476
3477
3473
3479
3480
3501
3502
3503
3505
3506
3507
3508
3509
3510
3519
UBC
(x 10~3/imi*3)
11.4
17.6
13.8
11.4
7.3
13.6
15.7
9.2
13.5
11.1
11.9
10.4
12.8
11.7
13.9
9.6
14.6
11.6
14.6
13:2
11.2
10.3
15.1
11.3
10.9
15.1
11.7
11.2
10.6
10.0
10.8
10.1
9.8
12.1
16.5
17.3
8.5
11.1
10.5
13.8
SEGS
(5 UBC)
11
18
24
16
7
17
13
21
16
40
11
23
10
19
14
14
17
14
28
29
21
15
45
15
9
12
21
16
11
12
19
19
18
17
33
3
14
24
21
12
BANDS
a use)
4
0
0
1
0
0
1
1
3
0
0
1
0
1
1
0
1
0
2
0
0
2
0
0
1
1
0
0
0
1
1
0
0 •
3
1
0
3
0
0
0
LYMPHS
(X UBC)
84
81
75
81
92
79
84
76
78
58
88
75
89
80
• 83
86
79
86
68
66
74
75
53
83
88
84
75
82
89
86
78
80
79
80
61
95
76
75
79
88
MONO
(X WBC)
0
0
1
0
0
3
2
0
0
1
1
0
0
0
1
0
2
0
1
4
1
6
1
2
2
1
2
0
0
1
1
1
1
0
0
1
6
1
0
0
EOS
(2 WBC)
1
1
0
2
0
1
D
2
3
1
0
1
1
0
1
0
1
0
1
1
4
2
1
0
0
2
2
2
0
0
1
0
2
0
0
1
1
0
0
0
D-67
70
-------
Scudy No. 5221.07
SUICHRDNIC TOXICITY OF META-CRESOL IN SPRAGUE DAULEY RATS
KALE HEMATOLOGY VALUES
[Terminal Sacrifice]
ANIMAL NO.
WBC
SEGS
DOSI LEVEL
0 mg/tcg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
(x
(x
BANDS LYHPHS MONO EOS
Cx 10A3/mnA3) (x 10A3/imf3)
-------
Study No. 5221.07
SU8CHRONIC TOX1CITY OF META-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE HEKATOLOGY VALUES
[Interim Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
ANIMAL NO.
3531
3532
3533
3534
3535
3536
3537
3533
3539
3540
3561
3562
3563
3564
3565
3566
3567
3S63
3569
3570
3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
R3C
(x 10*6/mmA3
7.S4
7.71
7.70
8.01
7.02
8.17
7.64
7.63
7.75
7.64
7.19
8.14
7.12
7.94
7.96
7.59
7.67
8,09
7.36
7.54
7.71
8.09
7.21
7.63
8.64
sc
sc
7.81
7.49
7.93
7.27
7.91
6.75
7.29
8.09
7.13
7.26
sc
6.B6
7.71
HGB
i) (g/dl)
16.0
15.6
15.3
15.4
14.1
15.5
15.9
15.4
15.7
15.6
15.0
15.6
15.2
16.6
15.3
15.8
15.1
16.3
1T. ,8
14.4
U.O
17.4
14.3
15.7
16.4
sc
sc
16.3
14.7
16.0
14.9
15.3
14.5
14.8
15.5
16.0
14.9
sc
15.2
14.9
HCT
cx)
42.3
42.5
41.6
39.4
37.3
43.2
42.9
40.8
42.8
42.3
40.7
42.9
40.1
44.3
42.7
43.4
41.0
44.6
42.7
39.3
43.6
45.1
39.9
42.4
45.6
sc
sc
45.2
40.0
44.4
40.3
40.0
40.1
39.7
44.3
43.0
39.9
sc
40.1
41.6
PT
(sec.)
11.2
11.6
12.0
7.0
11.3
11.3
11.4
sc
11.2
11.5
11.3
13.5
11.7
12.6
10.7
12.8
11.7
6.3
11.1
12.3
12.2
10.6
10.8
11.9
11.9
10.7
10.3
12.7
11.1
10.6
12.5
10.1
11.9
12.0
5.8
11.4
12.1
11.4
10.9
11.4
APTT
(sec.)
33.7
31.9
29.4
45.3
29.5
29.2
30.6
sc
31.8
31.0
31.8
62.1
37.6
32.4
38.3
37.0
33.2
42.7
31.0
33.7
32.6
27.8
34.9
32.3
32.2
38.1
38.2
37.9
30.3
34.3
33.8
39.8
31.2
37.3
52.3
30.8
31.1
47.6
33.4
36.4
RETIC
(X rbc)
0.6
0.5
1.0
2.0
0.8
0.6
0.6
0.1
0.5
0.7
0.7
0.7
0.1
1.0
1.4
1.9
1.0
0.7
0.1
2.0
0.9
1.1
0.8
0.1
0.8
sc
sc
0.1
0.9
0.5
2.6
1.3
0.1
0.5
2.2
0.2
0.6
sc
0.6
0.3
D-69
f*j iTJ.
( ^
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF KETA-CRESOL IN SPRAGUE DAULETf RATS
FEMALE HEMATOLOGY VALUES
[Interim Sacrifice]
DOSI LEVEL
0 mg/kg/day
ANIMAL NO. U8C SECS BAUDS LYMPHS HOMO EOS
(x 10A3/rnnA3> tt UBC) (% UBC) (X WBC) (X UBC) IX WBC)
50 mg/kg/day
150 mg/kg/day
450 mg/ks/day
3531
3532
3533
3534
3535
3536
3537
3538
3539
3540
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3621
3622
3623
3624
3625
3626
3627
3623
3629
3630
8.5
12.1
9.6
10.0
10.6
10.5
10.5
10.3
14.7
9.9
12.1
10.9
11.1
10.7
11.1
14.3
13.6
7.9
14.5
9.4
13.3
13.7
8.4
9.6
9.5
sc
sc
13.2
8.8
11.4
13.9
12.9
9.6
9.3
8.2
11.1
11.5
sc
11.4
16.4
12
38
8
27
22
10
26
7
19
14
11
19
14
48-
23
12
14
13
15
10
24
19
14
12
17
sc
sc
8
4
26
5
15
14
38
30
24
6
sc
41
24
a
a
1
0
0
0
1
2
0
0
1
0
0
6
2
o
0
0
0
0
o
0
1
0
1
sc
sc
a
0
1
0
0
1
1
0
0
1
sc
0
0
86
60
86
73
76
90
70
90
79
86
87
81
85
44
70
37
86
81
80
89
76.
80
82
88
83
sc
sc
89
95
72
95
82
84
59
70
75
89
sc
59
71
0
1
5
0
2
0
2
1
0
0
0
0
0
1
4
0
0
0
5
0
0
1
2
0
0
sc
sc
0
1
1
0
3
1
2
0
1
2
sc
0
5
2
1
0
0
0
0
1
0
2
0
1
0
1
0
1
0
0
0
0
0
sc
sc
1
0
0
0
0
0
0
0
0
2
sc
0
0
D-70
-------
Study No. 5221.07
SU8CHRONIC TOXICITY OF META-CRESOt IN SPRAGUE DAULEY RATS
FEMALi HiMATOLQGY VALUES
[Interim Sacrifice]
DOSE LEVEL
50 mg/kg/day
15D rog/kg/day
450 mg/kg/day
ANIMAL NO.
3531
3532
3533
3534
3535
3536
3537
3538
3539
3540
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3591
3592
3593
3594 '
3595
3596 '
3597
3598
3599
3600
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
WSC
Cx 10A3/irar:
8.5
12.1
9.6
10.0
10.6
10.5
10.5
10.3
14.7
9.9
12.1
10.9
11.1
10.7
11.1
14.3
13.6
7.9
14.5
9.4
13.3
13.7
8.4
9.6
9.5
na
na
13,2
8.8
11,4
13.9
12.9
9,6
9.3
. 8.2
11.1
11.5
na
11.4
16.7
SEGS
S) (x 1Q*3/mm*3)
1.0
4.6
0.8
2.7
2.3
1.1
2.7
0,7
2.8
1.4
1.3
2.1
1.6
5.1
2.6
1.7
1.9
1.4
2.2
0.9
3,2
2.6
1.2
1.2
1.6
na
na
1.1
0.4
3,0
0.7
1.9
1.3
3.5
2,5
2.7
0.7
na
4.7
3.9
BANDS
-------
Study Mo. 5221.07
SUSCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE DAULEY RATS
FEMALE HEMATOLOGY VALUES
[Terminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
AHIMAL MO.
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
2601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
RBC
(x 10A6/mm*3
8.51
8.07
8.48
8.47
8.29
8.33
8.31
8.19
7.33
8.36
8.60
8.46
8.43
8.73
9.53
8.37
7.81
8.44
8.01
8.29
8.31
8.21
8.68
8.51
9.07
8.51
8.79
8.33
8.24
8.40
8.15
8.18
7.94
9.00
7.77
8.56
8.22
8.01
9,41
7.74
HC3
) <9/dl)
15.3
15.0
15.3
15.9
15.5
15.6
15.8
16.6
14.4
15.7
15.8
15.6
15.4
16.7
17.3
16.1
15.7
15.3
14.9
16.0
16.0
15.9
16.7
'15.8
16.5
16.0
17.1
15.8
15.8
16.3
15.5
15.0
14.9
17.1
15.3
16.3
15.8
14.3
16.6
15.7
HCT
(X)
43.2
41.3
44.1
46.5
44.4
45.2
44.5
46.6
39.2
44.8
45.9
43.7
44.2
47.3
47.8
45.0
43.3
42.3
41.4
45.4
45.7
44.2
45.2
46.2
47.6
44.8
50.1
43.8
45.2
45.4
44.3
42.0
43.1
49.0
43.5
47.6
43.8
39.8
47.3
44.3
PT
(sec.)
11.6
11.5
13.1
11.4
11,0
11.5
10.8
9.4
11.4
10.6
11-3
11.4
11.1
10.9
13.6
12.5
6.6
11.8
10.8
10.9
11.5
12.5
10.5
11.1
10. S
5.9
10.6
11.7
11.3
13.0
9.3
11.0
11.4
11.1
11.1
11.4
12.6
8.0
11.9
10.8
APTT
(sec.)
16.3
25.3
37.1
37.3
34.1
40.1
38.8
35.2
34.9
40.3
36.4
36.9
43.6
32.0
48.3
39.1
38.2
35.1
31.0
37.5
27.4
37.7
39.1
35.3
33.1
36.1
36.0
35.6
35.7
44.9
33.1
34.9
40.4
35.5
38.3
36.5
39.2
39.1
33.7
34.6
RET1C
1% rbcj
0.2
1.8
0.6
0.9
1.3
0.4
0.2
1.0
0.8
0.1
0.4
0.6
0.1
0.8
1.3
0.4
0.5
0.7
0.2
0.8
0.7
0.2
0.3
1.0
1.5
0.1
0.4
0.6
1.7
1.5
1.0
0.2
0.5
1.3
0.1
0.8
1.0
0.2
1.0
0.4
D-72
175
-------
Study No. 5221.0?
SUiCHRONIC TQXiClTY OF META-CSESOL IN SPRAGUE DAULEY RATS
FEMALE KEMATQLQGY VALUES
fTerminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/dav
450 mg/ki/day
ANIMAL NO.
3541
3542
3543
3544
3545
3546
3547
354S
3549
3550
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
3601
3602
3603
3604
3605
3606
3607
3608
36C9
3610
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
UBC
(x 10A3/um*3>
8.7
8.5
6.5
5.8
8.0
8.5
10.6
10.7
a. 2
11.6
6.7
8.5
10.4
7.2
13.0
13.7
11.0
7.6
9.9
6.2
11.4
7.1
11.0
8.3
10.2
6.4
7.9
13.5
8.0
9.0
9.8
7.0
9.6
11.8
4.7
13.2 '
9.9
6.3
5.6
8,6
SEGS
c% yao
13
12
18
15
18
8
11
13
18
28
14
17
11
11
13
19
40
25
8
11
7
14
9
14
a
48
15
8
19
10
9
16
5
35
10
16
6
26
14
23
BANDS
a UBC}
0
1
0
3
0
1
0
1
0
0
0
0
0
2
3
0
1
0
0
0
1
0
3
0
2
0
1
0
t
0
0
0
3
1
0
0
2
4
0
0
LYMPHS
a '-so
85
as
82
80
75
88
S3
84
78
70
82
82
85
85
82
79
58
75
89
87
91
84
84
84
88
52
83
91
77
89
91
83
90
59
18
82
89
67
84
75
MONO
{% WBC}
1
0
0
0
6
2
4
1
1
0
2
1
0
0
1
2
0
0
2
2
0
1
4
1
0
0
1
0
2
0
0
0
2
2
2
0
0
0
1
0
EOS
(% UB
1
2
0
2
1
1
2
1
3
2
2
0
4
2
1
0
1
0
1
0
1
1
0
1
2
0
0
1
1
1
0
1
0
3
0
2
3
3
1
2
D-73
•*. **i
-i 7
-------
Study No. 5221.07.
SUBCHRONIC TQXICITY OF META-CRESOL IN SPRAGUE DAULEY RATS
FEMALE HEHATOLOGY VALUES
^Terminal Sacrifice!
DOSE LEVEL
0 ing/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
ANIMAL HO.
3541
3542
3543
3544
3545
3546
3547
3543
3549
3550
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
3601
3602 .
3603
3604
3605
3606
3607
3608
3609
3610
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
use
(x 10A3/mnT3) tx
8.7
8.5
6.5
5.3
8.0
8.5
10.6
10.7
8.2
11.6
6.7
8.5
10.4
7.2
13.0
13.7
11.0
7-6
9.9
6.2
11.4
7.1
11.0
8.3
10.2
6.4
7.9
13.5
8.0
9.0
9.8
7.0
9.6
11.8
4.7
13.2
9.9
6.3
5.6
8.6
SEGS
10"3/rmr3
1.1
1.0
1.2
0.9
1.4
0.7
1.2
1.4
1.5
3.2
0.9
1.4
1,1
0.8
1.7
2.6
4.4
1.9
o.a
0.7
0.8
1.0
1.0
1.2
0.8
3.1
1.2
1.1
1.5
0.9
0.9
1.1
0.5
4.1
0.5
2.1
0.6
1.6
o.a
2.0
BANDS
) (x 10*3/mmA3)
0.0
0.1
0.0
0.2
0.0
0.1
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.4
0.0
0.1
0.0
0.0
0.0
0.1
0.0
0.3
o.o
0.2
0.0
0.1
0.0
0.1
0.0
0.0
0.0
0.3
0.1
0.0
0.0
0.2
0.3
0.0
0.0
LTMPHS
-------
Stcdy No. 5221,07
SUSCHROMIC TOXtClTY 0? HETA-CSESOL JN SPRACUE OAWLEY RATS
MALE CLINICAL CHEMISTRY VALUES
{Interim Sacrifice;
DOSE LEVEL
ANIMAL NO. GLU BUN 5G?T SCOT T PSO ALB GLCS AIS/CLOS CHOL
-------
Study No. 5221.07
SUBCHRONIC TOXiCITY OF H6TA-CSESOL IN SFRAGUi DAUlETf RATS
HALE CLINICAL CHEHISTRY VALUES
[Interim Sacrifice]
DOSS LEVEL
ANIMAL NO. D BIL T BIL Na K Cl ALX FHOS CC2 CSEAT P«OS
(mg/dl) (mg/dl) (Meq/l) (Heq/L) (Keq/l) (!u/l> (Heq/tJ
-------
Study No. 5221.07
SUBCHROMIC TOXICtTY OF KETA-CSESOL IN SPRAGUE DAHLEY RATS
MALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
DOSS LEVEL
0 mg/kg/day
ANIMAL NO. GLU BUM SGPT SCOT T PRO ALB
(mg/dl) (fflg/dtj Uu/l> (lu/l)
GL08
ALB/GLOB CHOL
(ratio) (mg/dl)
50 mg/ka/day
150 mg/kg/day
450 mg/ki/day
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3441
3442
3443
3444
3445
3446
3447
3448
3449
34SO
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3501
3502
3503
3505
3506
3507
3508
3509
3510
3519
243.2
268.7
264.9
302.4
205.8
178.1
133.7
185,4
183.6
221.3
185.9
184.6
288.6
233.2
240.4 .
182.3
246.2
189. S
269.6
271.7
230.2
206,3
267.2
147.7
258.1
326.8
230.4
277.1
250.5
217.6
312.9
206.0
222.4
201.7
230,3
213.8
197.2
276.2
206.2
266.7
12,3
14.0
17.0
9.1
14.3
13.2
14.7
10.2
13.2
14.4
13.1
12.5
13.5
13.8
13.9
15.2
18.3
10.6
11.5
13.0
13.6
16.1
19.7
14.4
15,7
11.3
11.1
14.4
11,5
12.0
17.5
10.1
14.3
14.1
13.1
13.8
16.3
13.3
15.3
11.5
30
32
23
26
21
37
QMS
27
29
29
27
27
28
22
29
32
25
26
24
31
34
46
34
40
99
40
25
30
31
23
32
38
32
37
35
23
36
33
19
29
79
86
72
79
69
102
68
63
64
83
77
73
63
61
81
85
76
66
68
78
83
117
90
122
130
93
52
94
96
93
92
69
108
96
70
62
125
72
73
92
7.1
6.2
6.8
7.0
6.7
7.2
6.0
7.0
6.7
6.5
7.4
6.2
5.6
5.7
7.0
7.0
7.5
6.9
7.3
6.6
6.9
7.2
7.1
6.0
7.7
7.5
6.5
7.7
6.8
7.6
5.8
6.6
7.2
7.2
7.6
6.1
7.3
6.6
6.3
4.9
3.9
3.8
3.7
4,1
3.7
4.1
3.8
3.8
3.4
4.1
4.2
3.8
3.6
3.9
3.9
4.0
4.0
3,7
4,0
3.9
3.9
4.2
3.5
4.1
4.2
4.0
3.6
5.4
3.8
4.5
3.9
3.7
4.2
4.0
4.1
3.7
4.4
3.6
4.0
3.6
3.2
2.4
3.1
2.9
3.0
3.1
2.2
3.2
3.3
2.4
3.2
2.4
2.0
1.8
3.1
3.0
3.5
3.2
3.3
2.7
3.0
3.0
3.6
1.9
3.5
3.5
2.9
3.2
3.0
3.1
1.9
2.9
3.0
3.2
3.5
2.4
2.9
3.0
2.8
1.3
1.219
1.583
1.194
1.414
1.233
1.323
1.727
. 1.188
1.030
1.708
1,313
1.583
1.800
2.167
1.258
1.333
1.143
1.156
1.2J2
1.444
1.300
1.400
0.972
2.158
1.200
1.143
1.241
1.688
1.267
1.452
2.053
1.276
1.400
1.250
1.171
1.542
1.517
1.200
1.429
2.769
67.0
53.8
54.4
46.9
83.2
39.7
65,2
55.7
51.2
54.7
53.2
73.7
65.6
68.3
60.8
47.7
64.9
46:5
109.6
56.-
75.1
73.3
56.9
73.0
51.6
55.5
47.4
106.1
49.2'
75.9
52.9
48.7
67.8
50.5
76.9
66.5
75.6
48.4
62.3
48,8
D-77
80
-------
SUBCHRON1C TOXICITY OF META-CRESOL IN SPRACUE DAULEY PATS
HALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
SO nig/kg/day
150 mgAg/day
450 mgAs/day
ANIMAL NO.
3411
3412
3413
3414
3415
3416
3417
3413
3419
3420
3441
3442
3443
3444
3445
3446
3447
.3448
3449
3450
3471
3472
3473
3474
3473
3476
3477
3473
3479
3420
3501
3502
3503
3505
3506
3507
3508
3509
3510
3519
D BIL
3
QNS
6.0
7.2
5.9
QNS
6.0
QNS
6.3
8.1
QNS
QNS
Cl
(Heq/l)
103
QNS
105
103
105
103
QNS
102
101
QNS
10£
QNS
103
104
100
103
102
101
107
QNS
101
102
105
QNS
98
100
10£
QNS
104
QNS
105
105
107
QNS
1M
QNS
102
101
QNS
GNS
ALK PHOS
(lu/l)
S9
70
65
46
51
73
45
100
37
44
105
•72
89
123
99
80
120
36
81
64
60
47
58
126
66
70
40
25
87
84
109
103
61
61
133
58
79
94
51
103
CQ2
23
QNS
24
22
21
31
QNS
ia
27
QNS
26
QNS
20
22
29
22
19
25
18
QNS
21
32
24 •
QNS
23
26
18
QNS
28
QNS
18
20
30.
QNS
20
QNS
33
16
QNS
CMS
GREAT
Cmg/dl)
0.79
QNS
0.79
0.70
0.73
0.67
QNS
0.64
0.70
0.23
0.64
0.66
0.67
0.69
0.97
0.72
0.83
0.75
0.73
0.68
0.76
0.85
0.79
0.66
0.79
0.98
Q.66
0.79
0.80
0.70
0.77
0.63
0.89
0.66
0.83
QNS
1.03
0.67
QNS
0.73
PHOS
(mg/dL)
7.9
QNS
3.7
3.4
3.1
10-0
QNS
3.0
3.2
QNS
8.3
QNS
7.1
7.3
8.4
8.9
9.1
7.0
10.2
QNS
3.3
9.1
3.6
QNS
3.5
7.1
8.7
QNS
7.4
5.4
8.4
a. 5
9.0
8.7
9.4
QNS
8.1
9.3
QNS
9.4
D-78
Si
-------
Study Mo. 5221.07
SUBCHRCNIC TOXIC1TY OF META-CRESOL IN SPRAGUE OAULEY RATS
FEMALE CLINICAL CKEHISTRY VALUES
(Interim Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 flig/kg/day
150 mg/kg/day
450 mg/ks/day
AM I HAL NO.
3531
3532
3533'
3534
3535
3536
3537
3538
3539
3540
'356V
3562
3563
3564
3565
3566
3567
3568
3569
3570
3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
GLU
{rng/dJ )
193.2
113.6
278.3
246.6
196.0
198.2
114.9
163.5
338.4
205.3
159.1
272.9
166.8
138.5
158.6
227.2
318.6
152.4
195.3
330.2
323.3
120.7
242.3
144.6
195.7
150.3
277.2
121.0
192.8
98.6
511.6
208.4
142.0
148.6
266.9
199.3
139.8
106.1
349.9
230.5
BUN
Cmg/dL)
16.0
15.4
20.4
23.2
20.0
18.4
22.0
17.2
21.4
22.5
22.5
21.3
17.2
10.7
14.3
19.0
21.3
22.4
23.8
23.0
26.2
25.8
20.6
17.3
26,8
20.1
19.7
18.7
15.7
24.9
14.9
21,7
16.2
17.3
21.3
17.5
19.0
21.3
19.9
25.2
SGPT
Clu/D
39
25
29
51
26
16
25
19
31
32
17
36
30
22
42
43
41
45
30
35
25
19
43
25
43
41
49
22
35
QMS
40
67
22
25
43
27
22
57
; 20
36
SCOT
nu/u
93
89
70
92
86
81
70
80
59
66
68
69
99
74
80
76
61
85
74
84
72
76
63
88
63
80
74
97
61
QMS
57
111
aa
84
53
115
78
85
83
55
T PRO
(S/dl)
7.2
6.6
8.2
8.6
6.6
6.3
7.2
6.6
8.8
8.1
6.4
8.3
7.6
7.2
8.6
8.3
10.2
8.2
7.2
8.0
8.3
6.2
9.1
6.9
8.9
7.9
8.7
7.2
8.1
6.5
8.4
9.9
6.3
6.5
9.3
6.5
6.8
7.8
7.9
9.0
AL8
(g/dl)
4.2
3.6
4.4
4.2
3.7
4.2
4.1
3.9
5.4
4.3
3.5
5.0
4.4
4.0
4.4
4.8
6.0
4.3
4.2
4.6
4.7
3.6
4.5
3.8
5.0
4.4
4.8
4.0
4.5
3.9
4.7
4.0
3.7
3.6
4.6
3.3
3.9
4.4
4.2
5.6
GLOB
(g/dl>
3.0
3.0
3.8
4.4
2.9
2.6
3.1
2.7
3,4
3.8
2.9
3.3
3.2
3.2
4.2
3.5
4.2
3.9
3.0
3.4
4.1
2.6
4.6
3.1
3.9
3.5
3.9
3.2
3.6
2.6
3.7
5.9
2.6
2.9
4.7
2.7
2.9
3.4
3.7
3,4
ALB/GL03
(ratio)
1.400
1.200
1.158
0.955
1.276
1.615
1.323
1.444
1.588
1.132
1.207
1.515
1.375
1.250
1.048
1.371
1.429
1.103
1.400
1.353
1.146
1.335
0.978,
1.226
1.282
1.257
1.231
1.250
1.250
1.500
1.270
0.678
1.423
1.241
0.979
1.407
1.345
1.294
1.135
1.647
CHOI
(mg/dl)
95.9
75.5
106.7
105.8.
71.2
104.9
83.9
99.8
134.7
113.9
84.6
106.1
115.4
68.5
114.4
84. 7
123.4
118.3
90.0
94.9
120.5
71.8
141.5
77.9
109.0
94.5
119.4
ea.2
102.7
76.5
162.9
146.5
73.4
88.0
161.1
100.2
99.7
92. S
107.0
123.1
D-79
,82
-------
Study No. 5221,07
TOX1C1TY OF HETA-CRESOL IH SPRAGUE DAULEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Interim Sacrifice}
DOSE LEVEL
0 mgAg/day
50 png/kg/day
150
450 mg/kg/day
ANIMAL NO.
3531
3532
3533
3534
3535
3536
3537
3533
3539
3540
3561
3562
3563
3564
3565
3566
3567
356S
3569
3570
3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3621
3622
3623
3624
3625
3626
3627
3623
3629
3630
0 BIL
:mg/dl)
0.02
0.06
0.02
0.02
0.05
0.03
0.01
0.03
0.07
0.00
0.03
0.01
0.03
0.02
0.02
0.06
0.02
0.00
0.08
0.07
D.D1
0.03
0.04
D.03
0.01
0.01
0.01
0.07
0.01
0.03
O.C4
0.01
0.06
0.02
0.00
0.06
0.01
0.02
0.07
0.07
T BIL
-------
Study No. 5221.07
SUSCHRONIC TOXICITr OF META-CRESOL IX SPRAGUE OAWLEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
ANIMAL NO.
3541
3542
3543
3544
3545
3546
3547
3548
3549
355Q
3571
3572
3573
3574
3575
3576
3577
3578
3579
35BO
3601
3602
3603
3604
3605
3606
3607
36C8
3609
3610
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
GLU
(mg/dl)
217.4
215.2
260.6
247.7
223.6
184.7
165.2
156.3
246.7
239.5
202.7
Z07.2
253.8
239.8
174.1
205.1
184.4
202.2
153.7
217.3
169.5
203.1
187.0
255.7
119.0
181.8
134.6
248.7
218.0
274.1
185.4
183.0
215.2
209. 6
170.2
172.8
163.6
309.2
149.0
307.5
SUM
C mg/dl }
25.0
12.0
16.1
16.4
11.7
15.0
12.8
13.7
20.5
17.5
14.0
12.8
11.6
19.7
15.3
"18.7
13.4
16.4
13.1
11,0'
11.9
15.1
17.0
19.9
21.8
13.8
12.5
15.0
11.6
17.9
13.2
14.8
11.7
14.8
14.0
22.4
15.1
11.0
13.9
12.2
SGPT
Uu/U
38
37
23
38
26
33
31
36
24
92
41
52
38
24
42
25.
30
22
39
20
30
30
22
34
26
20
23
27
26
21
21
29
53
31
23
48
24
32
43
29
SCOT
tlu/U
99
96
84
124
89
102
86
84
68
202
95
B4
85
82
89
93
79
80
93
68
95 '
64
85
104
73
58
83
101
m
66
74
77
118
85
66
104
65
68
86
92
T PflO
(g/dl)
8.1
6.3
7.7
7.9
7.7
7.7
6.3
6.7
6.B
7.9
8.0
8.0
6.9
7.2
7.2
8.1
7.3
6.8 -
6.2
8.0
7.7
7.9
7.5
7.6
7.1
7.1
5.9
6.9
7.0
6.9
5.9
7.1
7.2
7.6
7.2
7.8
7.2
8.4
6.3
7.6
ALi
Cg/dl)
4.9
3.4
4.4
4.8
4.8
5.0
4.1
4.4
3.9
5.1
5.0
4.6
4.6
4.4
3.9
4,5
4.0
3.8
3.8
4.9
4.8
4.9
3.9
4.9
4.2 '
4.2
4.3
4.0
4.3
4.6
3.9
4.1
4.7
4.7
4.2
5.0
4.3
4.9
4.7
5.0
GLOB
3.2
2.9
3.3
3.1
2.9
2.7
2.2
2.3
2.9
2.8
3.0
3.4
2.3
2.8
3.3
3.6
3.3
3.0
2.4
3.1
2.9
3.0
3.6
2.7
2.9
2.9
1.6
2.9
2.7
2.3
2.0
3.0
2.5
2.9
3.0
2.8
2.9
3.5
1.6
2.6
ALB/GLOB
(ratio)
1.531
1.172
1.333
1.548
1.655
1.852
1.864
1.913
1.345
1.821
1.667
1.353
2.000
1.571
1.182
1.250
1.212
1.267
1.583
1.5S1
1.655
1.633
1.033
1.815
1.448
1.448
2.687
1.379
1.593
2.000
1.950
1.367
1.880
1.621
1.400
1.786
1.413
1.400
2.938
1.923
CHOL
-------
Study No. 5221.I)/
SUBCHROM1C TOXICITT OF META-CRESOL IN SPRAGUE OAULEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
DOSE LEVEL
0 mgAg/day
50 mg/kg/day
150 mgAg/day
450 mg/lcg/day
ANIKAl NO.
3541
3542
3543
3544
3545
3546
3547
3543
3549
3550
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3631
3632
3633
3634
3635
3636
3637
3633
3639
3640
D B1L
Cmg/dU
0.00
0.02
0.00
0.01
0.03
0.04
0.01
0.01
0.01
0.01
0.07
o.co
0.01
p. 00
0.00
0.04
0.02
O.OQ
0.01
'0.16
0.06
0.02
O.CO
0.01
O.QO
0.01
0.00
0.03
0.00
0.01
0.02
0.01
0.26
0.04
0.11
0.00
0.00
0.00
0.00
0.06
T B1L
Cmg/dl)
0.14
0.11
0.06
0.13
0.16
0.27
0.20
0.19
0.07
0.13
0.15
0.37
0,26
0.07
0.09
0.13
0.15
0.04
0.22
0.04
0.24
0.17
0.15
0.15
0.13
0.10
0.14
0.17
0.16
0.15 '
0.13
0.12
0.16
0.27
0.04
0.20
0.09
0.05
0.11
0,22
Ca
Cmg/dU
14.0
12.6
12.6
14.0
9.9
10.6
6.9
10.4
10. 6
11.0
11.3
11.4
10.2
12.3
11.1
11.0
11.8
,12.4
6.9
9.9
10.3
11.7
10.6
11.5
12.5
9.9
10.1
11.3
a.2
12.4
7.0
12.1
10.8
10.2
10.5
11.7
12.6
13.9
11.6
10.8
Na
(Heq/O
142
143
144
144
QNS
147
QNS
QNS
143
QNS
147
QNS
147
143
142
146
142
142
QNS
150
QNS
146
QNS
147
155
143
143
143 ,
QNS-
141
QNS
146
147
.QNS
144
QNS
144
142
133
QNS
X
(Meq/t)
5.6
7.3
6.4
8.7
QNS
7.8.
QNS
QNS
7.7
QNS
6.2
QNS
6.0
6.6
9.6
6.8
7.5
7.1
QNS
6.4
QNS
5.- 9
QNS
9.3
8.9
6.8
9.4
6.7
QNS
7.0
QNS
7.0
7.2
QNS
7.5
QNS
7.7
5.3
9.g
QNS
Cl
-------
Study No. 5221.07
SUBCHRCHIC TOKICITT OF HETA-CSESDL IN SPRAGUE OAULEY RATS
MALE ORGAN UEIGHT DATA (93
[Terminal Sacrifice]
ANIMAL NO. HEART LIVES SPLEEN K1DNEY-LFT KIDNiY-RT
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
3441
3442
3443
3444
3445
3446
3447
3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
2.038
1.992
1.933
2.023
1.720
1.831
1.601
1.651
1.907
1.612
'2.013
2. 385
1.645
1.747
1.771
1.601
1.635
1.696
1.788
1.625
1.701
2.095
1.686
2.053
1.773
1.951
1.S97
2.042
2.290
2.093
2.001
1.750
1.525
2.127
1.567
1.789
1.630
1.665
1.852
1.666
21.503
19.033
17.491
17.071
15.392
16.403
13.979
20.427
17.690
14.292
21.558
24.654
17.683
18.119
18.281
17.270
20.387
16.166
17.647
18.839
18.370
19.711
17.704
18.965
17.295
16.662
17.440
17.791
e
19.015
18.542
23.033
15.535
19.904
16.612
18.946
16.217
13.363
16.397
18.729
0.874
0.940
0.798
0.840
0.861
0.698
0.920
0.916
0.893
0.579
0.787
1.051
0.824
0.862
0.784
0.760
0.776
0.738
0.678
0.808
0.753
0.770
0.672
0.682
0.651
0.711
0.710
0.761
0.934
0.869
0.809
1.056
0.705
1.091
0.791
0.666
0.653
0.923
0.802
0.795
2.246
2.369
2.057
2.076
1.784
1.639
1.628
2.221
1.982
1.803
2.285
2.379
2.065
1.961
2.218
1.811
2.327
2.191
2.127
1.775
1 .940
2.231
1.456
2.421
1.714
1.988
1.8E8
2.134
2.272
2.167
2.012
2.196
1.730
2.183
1.913
2.032
1.633
2.0C8
1.530
2.108
2.244
2.353
1.945
2.122
1.989
2.060
1.693
2.157
2.1S9
1.960
2.213
2.481
2.106
1.904
2.143
1.878
2.333
2,239
2.024
1.881
1.953
2.236
1.619
2.285
1.796
2.040
1.790
1.948
2.227
2.158
1.925
2.297
1.747
2.252
2.162
2.007
1.730
2,020
1.578
2.282
D-83
.15
-------
Study No. 5221.07
SU3CHRON1C TOX1CITY OF META-CRESOL IN SPRAGUE DAWLEY RATS
HALE ORGAN WEIGHT DATA Cg)
[Terminal Sacrifice!
ANIMAL NO. TESTIS-LFT TESTIS-RT ADRENALS BRAIN THY./PARA. TERM. UGT.
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3423
3429
3430
3441
3442
3443
3444
3445
3446
3447
3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3453
3459
3460
1.730
1.794
1.329
1.855
1.735
1.754
1.722
1.913
1.702
1.578
2.0S9
1.675
1.S22
1.805
2.029
1.607
1.702
3.347
1.944
1.543
1.670
1.701
1.6S9
1.869
1.743
1.969
1.363
1.706
1.875
1.815
1.673
1.6S1
1.344
1.760
1.667
1.795
1.641
1.916
1.625
1.810
1.744
1.676
1.826
1.833
1.734
1.834
1.731
1.728
1.743
1.561
1.999
1.601
1.877
1.846
1.975
1.640
1.610
3.731
1.975
1.556
1.703
1.709
1.705
1.319
1.621
1.B60
1.355
1.329
1.902
1.751
1.786
1.700
1.782
1.623
1.628
1.731
1.774
1.763
1.654
1.773
0.078
0.082
0.078
0.093
0.071
0.067
0.120
0.093
0.064
0.093
0.065
o.oaa
0.059
0.044
0.037
0.070
0.068
0.063
0.068
0.096
0.066
0.063
0.072
0.072
0.057
o.oao
0.074
0.062
0.095
0.091
0.083
0.092
0.061
0.039
0.038
0.074
0.076
0.055
0.071
0.055
2.186
2.356
2.363
2.232
2.232
2.261
2.260
2.184
2.283
2.035
2.182
2.371
2.252
2.237
2.298
2.164
2.427
2.200
2.26r.
2.155
2.424
2.319
2.236
2.164
2.197
2.247
2.168
2.376
2.302
2.251
2.263
2.199
2.134
2.283
2.1S7
2.261
2.145
2.340
2.373
2.291
0.042
0.052
0.056
0.065
0.042
0.025
0.061
0.052
0.039
0.104
0.018
0.031
0.024
0.043
0.032
0.022
0.023
0.043
0.024
0.031
0.032
0.033
0.051
0.039
0.043
0.037
0.041
0.032
0.020
0.061
0.033
0.031
0.027
0.040
0.040
0.024
0.033
0.037
0.034
0.028
609
604
530
569
569
495
599
527
566
429
595
691
553
569
565
495
548
546
526
504
467
583
519
562
531
518
524
515
596
553
555
599
519
586
546
574
539
613
545
570
D-84
187
-------
Study No. 5221.07
SUBCHRONIC TOXtCITY OF HETA-CRESOL IN SPRAGUE DAWLEY RATS
HALE ORGAN UEIGHT DATA
-------
Study No. 5221.07
SUBCHRGNIC TOX1CITY CF NETA-CRESOL IS SPRAGUE OAWLEY RATS
MALE ORGAN WEIGHT DATA Cg)
[Terminal Sacrifice]
ANIMAL NO. TESTIS-LFT TESTIS-RT ADRENALS IRAIN THY./PARA. TERM, UGT.
DOSE LEVEL
150 ma/kg/day
450 mg/kg/day
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3481
3482
. 3483
3484
3485
3486
3487
348S
, 3489
3490
3501
3502
3503
3505
3506
3S07
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
1.680
1.672
1.812
1.852
1.691
1,652
1.740
1.038
1.798
1.796
1.8D1
1.633
1.707
1.868
1.795
1.655
1.824
1.674
1.809
1.845
1.790
1.667
1.832
1.727
1.739
1.756
1.761
1.911
1.631
1.625
1.671
1.693
1.648
1.632
1.778
1.616
1.872
1.698
1.584
1.726
1.621
1.765
1.887
1.683
1.565
1.784
1.867
1.772
1.775
1.833
1.638
1.701
1.883
1.723
1.642
1.362
1.656
1.802
1.840
1.721
1.601
1.834
1.792
1.721
1.704
1.768
2.790
1.717
1.646
1.672
1.616
1.703
1.602
1.106
1.558
1.828
1.653
1.707
0.083
0.068
0.044
0.081
0.063
0.078
0.044
0.080
0.072
0.086
0.075
0.079
0.070
. 0.059
0.057
O.D81
0.050
0,081
0.075
0.072
0.096
0.051
0.071
0.088
0.069
0.077
0.074
0.094
0.070
0.070
0.053
0.044
0.031
0.074
0.075
0.103
0.061
0.099
0.066
2.248
2.305
2.320
2.283
2.347
2.282
2.242
2.417
2.1SO
2.203
2.273
2.310
2.394
2.188
2.307
2.222
2.427
2.129
2.026
2.232
2.298
2.737
2.107
2.367
2.618
2.406
2.187
2,395
2.203
2.256
2.074
2.004
2.277
2.202
2.207
2.214
2.200
2.331
2.078
0.043
0.036
0.019
0.030
0.031
0.050
0.031
0.041
0.033
0.026
0.031
0.028
0.027
0.025
0.025
0.036
0.026
0.028
0.020
0.032
0.049
0.032
0.030
0.038
0.046
0.047
0.033
0.049
0.026
0.038
0.019
0.023
0.035
0.012
0.052
0.021
0.024
0.044
0.042
478
542
525
547
483
422
531
550
537
461
542
585
581
514
464
445
481 '
541
493
485
489
431
511
492
456
575
508
530
534
545
450
450
494
442
429
470
448
458
416
D-86
Q Q
c3 J
-------
Study No. 5221.07
SUBCHRONIC TOXIC1TY OF META-CRESQL IN SPRAGU1 DAULET RATS
RELATIVE HALE ORGAN WEIGHT DATA {% Terminal Body Weight)
(Terminal Sacrifice]
ANIMAL NO. HEART LIVER SPLEEN KIDNEY-LFT K1DN6Y-RT
DOSE LEVEL
0 rag/kg/day
50 mg/ks/tlay
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
3441
3442
3443
3444
3445
3446
3447
3443
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
0,335
0.330
0.366
0.356
0.302
0.370
0.267
0.313
0,337
0.376
0.339
0.345
0.297
0.307
0.313
0.323
0.298
0.311
0.340
0.322
0.364
0.3S6
0.325
0.365
0.334
0.377
0.362
0.397
0.384
0.378
0.361
0.292
0.294
0.363
0.287
0.323
0.284
0.309
0.300
0.306
3.531
3.151
3.3CO
3.000
3.232
3.314
2.334
3.376
3.125
3.331
3.623
3.568
3.198
3.184
3.236
3.439
3.720
2.961
3.355
3.733
3.934
3.352
3.411
3.375
3.257
3.255
3.328
3.455
na
3.439
3.341
3.845
2.993
3.397
3.042
3.470
2.825
3.407
2.653
3.437
0.144
0.156
0.151
0.148
0.151
0.141
0.154
0.174
0.153
0.135
0.132
0.152
0.149
0.151
0.139
0.154
0.142
0.135
0.129
0.160
0.161
0.131
0.129
0.121
0.123
0.137
0.135
0.148
0.157
0.157
0.146
0.176
0.136
0.186
0.145
0.122
0.114
0.171
0.130
0.146
0.369
0.392
0.388
0.365
0.314
0.331
0.272
0.421
0.350
0.420
0.384
0.344
0.373
0.345
0.393
0.366
0.425
0.401
0.404
0.352
0.415
0.379
0.281"
0.431
0,322
0,384
0.349
0.414
0.381
0.392
0.363
0.367
0.333
0.373
0.350
0.372
0.284
0.373
0.248
0.387
0.368
0.390
0.367
0.373
0.350
0.416
0.283
0,409
0.381
0.457
0.372
0.359
0.381
0.335
0.379
0.379
0.426
0.410
0.385
0.373
0.418
0.380
0.312
0.407
0.338
0.394
0.342
0.378
0.374
0.390
0,347
0.383
0.337
0.384
0.396
0.368
0.301
0.375
0.255
0.419
D-87 I 9 0
-------
Study Mo. 5221.07
SUBCHRON1C TOXIC1TY OF META-CRESOL IN SPRAGUE DAULEY RATS
RELATIVE HALE ORGAN WEIGHT DATA
-------
Study Mo. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRACUE DAWLEY RATS
RELATIVE MALE ORGAN WEIGHT DATA (7. Terminal Body Weight)
[Terminal Sacrifice]
ANIMAL NO. HEART LIVER SPLEEN KIDNEY-LFT KIDNEY-RT
DOSE LEVEL
150 mg/kg/day
450 mg/lcg/day
3471
3472
3473
3474
3475
3476
3477
3473
3479
3480
3481
3432
3433
3434
3485
3486
3437
3433
3439
3490
3501
3S02
35 D3
3505
3506
3507
3503
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
0.425
0.311
0.345
0.365
0.324
0.373
0.316
0.344
0.305
0.388
C.346
0.327
0.296
0.328
C.353
0.346
0.360
0.336
0.332
0.3H
C.332
0.440
0.331
0.363
0.314
0.326
0.381
0.360
0.327
C.369
0.307
0.319
0.321
0.329
0.357
0.332
0.353
0.464
0.326
3.427
3.044
2.392
3.120
2.339
3.055
3.203
1.363
3.232
3.093
3.310
3.435
3.296
3.196
3.311
3.313
3.062
3.514
2.962
i.149
3.259
3.693
3.415
3.529
3. 284
3.679
3.320
3.5S3
3.526
3.047
3.033
2.964
3.332
3.003
3.234
3.476
3.365
4.598
3.390
0.143
0.142
0.153
0.126
0.119
0.145
0.114
0.120
0.145
0.107
0.122
0.155
0.118
0.155
0.149
0.159
0.213
0.144
0.121
0.156
0.128
0.166
0.134
0.159
0.169
0.152
0.147
0.164
0.164
0.145
0.183
0.132
0.159
0.145
0.156
0.154
0.126
0.229
0.129
0.415
0.401
0.343
0.347
0.404
0.423
0.328
0.371
0.349
0.491
0.362
0.400
0.391
0.319
0.400
0.411
0.433
0.385
0.338
0.385
0.199
0.387
0.369
0.467
0.369
0.400
0.363
0.439
0.400
0.335
0.333
0.342
0.362
0.362
0.402
0.357
0.382
0.515
0.497
0.446
0.394
0.323
0.334
0.352
0.423
0.335
0.332
0.37S
0.492
0.352
0.393
O.;K
0.299
0.413
0.393
0.404
0.405
0.397
0.377
0.207
0.465
0.349
0.466
0.378
0.433
0.381
0.437
0.372
0.326
0.398
0.363
0.330
0.384
0.439
0.360
0.402
0.525
0.469
D-89 1 8
-------
Study No. 5221.07
SUBCHRQNIC TOX1CITY OF MgTA-CRESQL IN SPRAGUE DAULEY RATS
RELATIVE HALE ORGAN WEIGHT DATA (X Terminal Body yeight)
[Terminal Sacrifice]
AN1KAL NO. TESTIS-LFT TESTIS-RT ADRENALS BRAIH THY./PARA.
DOSE LEVEL
150 cg/kg/day
450 mg/kg/day
3471
3472
3473
3474
3471
3476
3477
3478
3479
34BO
3481
3482
3483
3484
3485
3486
3487
3488
3489
3490
35C1
35C2
3503
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
0.351
0.308
0.345
0.339
0.35D
0.391
0.328
0.189
0,335
'0.390
0.332
0.279
0.294
0.363
0.387
0.372
0.379
0.3Q9
0.367
0.380
0.366
0.387
0.359
0.351
; 0.381
0.305
0.347
0.361
0.305
0.298
0.371
0.376
0.334
0.369
0.414
0.344
0.418
0.371
0.381
0.361
0.299
0.336
0.345
0.348
0.371
0.336
0.339
0.330
0.385
0.338
0.280
0.293
0.366
0.371
D.369
0.387
0.306
0.366
0.379
0.352
0.371
0.359
0,364
0.377
. 0.296
0.348
0.526 ,
0.322
0.302
0,372
0.359
0.34S
0.362
0.421
0.331
0.408
0.361
0.410
0.017
0.013
0.008
0.015
0.013
0.018
0.008
0.015
0.013
0.019
0.014
0.014
0.012
0.011
0.012
0.013
0.010
0.015
0.015 -
0.0i5
0.020
0.0':'.!
0.014
0.018
0.015
0.013
0.015
C.018
0.013
0.013
0.012
0.010
0.006
0.017
0.017
0.022
0.014
0.022
0.016
0.470
0.425
0.442
0.417
0.486
0.541
0.422
0.439
0.400
0.478
0.419
0.395
0.412
0.426
0.497
0.499
0.505
0.394
0.411
0.460
0.470
0.635
0.412
0.481
0.574
0.418
0.431
0.452
0.413
0.414
0.461
0.445
0.461
0,498
0.514
0,471
0.491
0.509
0.500
0.009
0.007
0.004
0.005
0.006
0.012
0.006
0.007
0.006
0.006
0.006
0.005
0.005
0.005
0.005
0.008
0.005
0.005
0,004
0.007
0.010
0.007
0,006
0,003
0.010
O.OQ8
0.006
0.009
0.005
0.007
0.004 .
0.005
0.007
0.003
0.012
0.004
0.005
0.010
0.010
D-90
-------
Study No. 5221.07
SUSCHSONIC TOXICJTY OF MSTA-C8ISOL IN SPRAGUi DAULEY RATS
FEHALi ORGAN HEIGHT DATA
(Terminal Sacrifice]
ANIMAL MO. HEART LIVER SPLEEM KiDNEY-LFT KIDNEt-RT
DCSE LEVEL
50 mg/kg/day
3541
3542
3543
' 3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
35S1
3582
35B3
3584
35S5
3586
3587
3588
3589
3590
1.197
1.111
1.133
1.925
1.257
1.065
1.064
1.109
1.101
1.001
1.037
1.008
1.019
0.950
0.976
1.143
1.271
1.035
0.911
1.024
1,044
1.231
1.041
0.934
1.188
0.993
1.068
1.D34
1.228
1.108
0.968
0.973
0.933
1.209
1.015
0.973
1,285
1.107
1.026
0.950
8,951
9.187
8.949
8.823
9.364
8.214
9.140
10.194
10.409
9.523
8.443
10.424
10.932
8.079
8.092
9.010
10.216
8.423
7.655
7.824
9.536
8.503
11.179
9.089
9.973
9.156
8.306
9.159
9.647
9.294
7.069
7.092
8.982
12.383
8.695
8.309
8.780
10.683
10.158
7.855
0.680
0-523
0.451
0.437
0.506
0.510
0.710
0.572
0.596
0.542
0.451
0.649
0.522
0.475
0.394
0.630^
0.667
0.462
0.550
0.493
0.634
0.439
0.681
0.540
0.527
Q.590
0.471
0.604
0.606
0.625
0.423
0.491
0.466
0.607
0.457
0.435
0.538
0.513
0.612
0.574
1.051
0.961
0.872
0.966
1.060
0.944
1.256
0.989
1.235
1.001
0.965
1.124
1.206
0.974
1.020
1.069
1.091
1.100
0.951
1.162
1.188
1.053
1.255
0.934
0.948
1.059
0.882
0.897
1.131
1.091
0.898
0.940
0.981
1.196
0.846
1.029
0.875
1.082
1.174
1.023
1.142
1.110
0.957
1.122
1.063
1.015
1.229
1.080
1.241
1.104
0.988
1.109
1.224
0.999
1.139
1.105
1.109
1.074
0.995
1.144
1.191
1.050
1.242
1.0S1
0.971
1.023
0.921
0.938
1.063
1.119
0.900
0.972
0.983
1.210
1.011
1.093
0.961
1.133
1.196
1.094
D-91
-------
Study No. 5221.07
SUBCHRCNIC TOXICITY OF HETA-CRESOL IN SPRACUE DAULEY RATS
FEMALE ORGAN WEIGHT DATA (3)
[Terminal Sacrifice]
ANIMAL NO. HEART LIVER SPLEEN KIDNEY-IFT K1DNEY-RT
DOSE LEVEL
150 mg/kg/day
450 nig/kg/day
3601
3602
3603
3604
3605
3606
3607
360B
3609
3610
3611
3612
3613
3614
3615
3616
3617
361S
3619
3620
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3648
3649
3650
1.035
1.588
0.892
1.008
1.099
1.065
0.983
1.256
1.152
1.116
0.916
1.144
1.006
1.013
0.870
1.060
1.134
O.B35 .
1.145
0,942
0.942
0.969
0.781
1.087
1.030
1.152
0.959
0.935
0.943
1.063
1.001
1.158
0.922
0.923
1.060
0.791
1.018
1.105
1.093
0.975
9.416
10.808
7.905
8.407
9.000
B.237
9.025
9.921
9.051
9.576
9.326
10.408
9.546
10.135
8.050
8.631
11.127
8.192
na
8.582
7.912
9.393
7.259
8.S36
8.460
10.954
8.669
9.839
10.105
8.851
7.581
10.820
8.135
6.459
10.102
8.776
10.001
10.343
11.662
7.633
0.601
0.522
0.457
0.543
0.582
0.504
0.324
0.621
0.617
0.489
0.531
0.489
0.565
0.495
0.574
0.566
0.447
0.427
0.505
0.414
0.420
0.448
0.424
0.480
0.424
0.593
0.484
0.420
0.382
0.417
0.396
0.550
0.546
0.409
0.605
0.407
0.652
0.630
O.S93
0.435
1.241
1.236
0.970
1.092
1.016
2.870
1.082
1.112
1.137
0.964
1.058
1.090
1.016
0.985
1.011
1.049
1.219
0.933
na
1.069
0.959
1.015
0.966
0.9S4
0.954
1.166
1.045
1.146
0.930
0.995
0.963
1.123
1.016
0.925
1.107
0.975
1.075
1.083
1.328
0.844
1.173
1.256
na
1.248
1.142
1.009
1.129
1.110
1.176
1.C29
1.081
1.140
1.070
1.113
1.123
1.092
1.207
0.947
na
1.018
0.979
1.104
0.945
1.023
0.983
1.241
1.093
1.094
1.019
1.099
1.059
1.152
1.059
0.962
1.184
1.008
1.113
1.121
1.456
0.838
D-92
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE ORGAN WEIGHT DATA (g)
[Terminal Sacrifice]
ANIMAL NO. OVARY-LFT OVARY-RT ADRENALS BRAIN THY./PARA. TERM. WGT.
DOSE LEVEL
0 mgAg/day
50 mgAg/day
3541
3542
3543
3544
3545
3546
3547
3543
3549
3550
3551
3552
3553
3554
3555
3536
3557
3553
3559
3560
3571
3572
3573
3574
3575
3576
3577
3573
3579
3580
3531
3582
3583
3534
3585
3536
3587
3588
3589
3590
0.056
0.075
0.080
0.049
O.C87
0.064
0.089
O.OB3
0.076
0.076
0.072
0.060
0.075
0.073
0.085
0.071
0.071
0.072
0.065
0.072
0.089
0.117
0.080
0.072
0.079
0.085
0.086
0.097
0.071
0.111
0.064
0.061
0.106
0.120
0.070
0.071
0.120
0.111
0.096
0.077
0.077
0.095
0.085
0.054
0.089
0.075
0.074
0.075
0.085
0.074
0.063
0.070
0.074
0.084
0.073
0.031
0.067
0.068
0.053
0.061
0.057
0.093
0.071
0.082
0.056
0.082
0.081
0.086
0.100
0.114
0.065
0.072
0.090
0.117
0.057
0.067
0.113
0.084
0.065
0.031
0.066
0.085
0.086
0.073
0.105
0.080
0.076
0.083
0.077
0.077
0.044
0.049
0.044
0.072
0.083
0.083
0.077
0.084
0.030
0.073
0.109
o.oas
0.032
0.075
0.072
0.092
0.053
0.082
0.076
0.089
0.079
0.064
0.070
0.076
0.071
0.362
0.112
0.114
0.054
0.089
2.025
2.192
1.900
2.061
2.087
2.003
2.273
2.190
2.113
2.065
2.056
2.034
1.890
2.041
1.998
2.118
2.200
2.175
1.972
2.166
2.268
1.992
2.095
1.989
2.150
2.183
1.973
2.051
2.052
2.062
2.077
2.040
2.078
2.097
1.960
2.136
2.099
2.199
2.045
2.019
0.061
0.023
0.033
0.031
0.029
0.024
0.019
0.021
0.020
0.015
0.022
0.030
0.025
0.026
0.017
0.023
0.026
0.025
0.029
0.021
0.021
0.035
0.026
0.031
0.033
0.034
0.032
0.076
0.017
0.032
0.020
0.018
0.023
0.032
0.017
0.015
0.033
0.031
0.031
0.031
282
242
243
263
261
278
2S6
304
264
273
280
297
297
275
240
284
285
279
243
251
282
265
294
262
273
288
255
279
265
271
246
254
242
305
255
243
275
27S
280
226
D-93
196
-------
Study No. 5221.07
SUBCHROWIC TOX1C1TY OF META-CRESOL IK SPRAGUE DAVILEY RATS
FEMALE ORGAN WEIGHT DATA (g)
[Terminal Sacrifice]
ANIMAL NO. OVARY-LFT OVARY-RT ADRENALS BRAIN THY./PARA. TERM. WGT.
DOSE LEVEL
150 mg/kg/day
450 mg/ leg/day
3601
3602
3603
3604
3605
3606
3607
3603
3609
3610
3611
3612
3613
3614
3615
3616
3617
361 B
3619
3620
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
364S
3649
3650
0.073
0.096
0.061
0.122
0.051
0.054
0.133
0.067
0.133
0.056
0.092
0.071
0.090
0.046
0.061
0.067
0.044
0.069
0.132
0.077
0.067
0.062
0.071
0.079
0.081
0.080
0.074
0.067
0.054
0.065
0.071
0.072
0.077
0.057
O.C96
0.062
0.153
0.095
0.063
0.047
O.OSO
0.080
0.068
0.082
0.086
0.102
0.105
0.063
0.114
0.069
0.074
O.OS3
0.080
0.060
0.063
0.083
0.063
0.07S
0.118
0.066
0.067
0.064
0.087
0.102
0.099
0.097
0.09Z
0.057
0.041
0.074
0.062
0.076
0.111
0.065
0.037
0.059
0.150
0.073
0.049
0.062
0.077
0.092
0.086
0.084
0.074
0.035
0.032
0.071
0.072
0.089
0.060
0.085
0.073
0.067
0.039
0.066
0.063
0.071
0.103
0.063
0.069
0.062
0.051
0.072
0.077
O.C75
0.068
0.079
0.034
0.067
0.053
0.064
O.C64
0.073
0.034
0.057
0.109
0.072
0.084
0.065
2.226
2.179
1.936
2.158
2.172
2.088
2.077
1.965
1.952
2.075
1.971
2.112
1.933
1.964
2.076
1.984
2. 078
2.065
2.209
2. 035
1.933
2.000
1.919
1.952
2.012
2.117
2.065
2.049
2.086
2.018
1.913
1.966
2.131
1.987
2.127
2.029
2.073
2.159
2.124
1.699
0.026
0.037
0.026
0.022
0.035
0.027
0.032
0.032
0.023
0.02B
0.027
0.034
0.021
0.016
0.023
0.030
0.029
0.019
0.024
0.016
0.028
0.028
0.017
0.028
0.022
0.028
0.024
0.014
0.031
0.030
0.022
0.021
0.022
0.028
0.033
0.017
0.032
0.020
0.024
0.030
297
292
239
255
267
264
259
304
265
256
293
299
261
256
242
269
321
249
262
245
222
264
209
267
233
293
248
247
210
235
233
332
244
202
273
243
277
311
304
243
D-9A
-------
Study Ho. 5221.07
SUBCHRON1C TOXICITT OF META-CRESOL IN SPRAGUE DAWLEY RATS
RELATIVE FEMALE ORGAN WEIGHT DATA <% Terminal Body
[Terminal Sacrifice]
ANIMAL NO. HEART LIVER SPLEEN KIDNEY-LFT KIDNEY-RT
DOSE LEVEL
0 mg/kg/day
50 mg/icg/day
3541
3542
3543
' 3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3571
3572
3573
3574
3575
3576
3577
3578
3579
3530
3531
3582
3583
3534
3585
3586
3587
3538
3589
3590
0.424
0.459
0.466
0.732
0.405
0.383
0.372
0.365
0.417
0.367
0.370
0.339
0.343
0.345
0.407
0.402
0.446
0.371
0.375
0.403
0.370
0.465
0.354
0.356
0.435
0.345
0.419
0.371
0.463
0.409
0.393
0.383
0.386
0.396
0.398
0.400
0.467
0.398
0.366
0.420
3.174
3.796
3. 683
3.355
3.588
2.955
3.196
3.353
3.943
3.4S3
3.015
3.510
3.681
2.938
3.372
3.173
3. 585
3.019
3.150
3.117
3.382
3.209
3.802
3.469
3.653
3.179
3.257
3.283
3.640
3.430
2.874
2.792
3.712
4. 060
3.410
3.419
3.193
3.843
3.628
3.476
0.241
0.216
0.186
0.166
0.194
0.183
0.248
0.188
0.226
0.199
0.161
0.219
0.176
0.173
0.164
0.222
0.234
0.166
0.^6
0.196
0.2^5
0.166
0.232
0.206
0.193
0.205
0.185
0.216
0.229
0.231
0.172
0.193
0.193
0.199
0.179
0.179
0.196
0.185
0.219
0.254
0.373
0.397
0.359
0.367
0.406
0.340
0.439
0.325
0.468
0.367
0.345
0.378
0.406
0.354
0.425
0.376
0.383
0.394
0.391
0.463
0.421
0.397
0.427
0.356
0.347
0.368
0.346
0.322
0.427
0,403
0.365
0.370
0.405
0.392
0.332
0.423
0.318
0.389
0.419
0.453
0.405
0.459
0.394
0.427
0.409
0.365
0.430
0.355
0.470
0.404
0.353
0.373
0.412
0.363
0.475
0.389
0.389
0.3B5
0.409
0.456
0.422
0.396
0.422
0.413
0.356
0.355
Q.361
0.336
0.401
0.413
0.366
0.383
0.406
0.397
0.396
0.450
0.349
0.408
0.427
0.484
D-95
198
-------
Study No. 5221.07
SUBCHRONIC TOXICITY Of META-CRESOL IN SPRAGUE DAWLEY RATS
RELATIVE FEMALE ORGAN WEIGHT DATA (X Terminal Body Weight)
[Terminal Sacrifice]
ANIMAL NO. HEART LIVER SPLEEN KIDNEY-LFT KIDNEY-RT
DOSE LEVEL
150 mg/kg/day
450 mgAg/day
3601
3602
3603
3604
3605
2606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3643
3649
3650
0.343
0.544
0.373
0.395
0.412
0.403
0.380
0.413
0.435
0.436
0.307
0.3S3
0.335
0.396
0.360
0.394
0.353
0.335
0.437
' 0.354
0.424
0.367
0.374
0.407
0.442
0.393
0.337
0.379
0.449
0.452
0.430
0.349
0.378
0.457
0.381
0.326
0.368
0.355
0.360
0.393
3.170
3.701
3.303
3.297
3.371
3.120
3.485
3.263
3.415
3.741
3.130
3.431
3.657
3.959
3.326
3.209
3.466
3.290
na
3.503
3.564
3.553
3.473
3.309
3.631
3.739
3.496
3.933
4.812
3.766
3.254
3.259
3.334
3.198
3.634
3.612
3.610
3.326
3.836
3.098
0.202
0.179
0.191
0.213
0.218
0.191
0.125
0.204
0.233
0.191
0.178
0.164
0.216
0.193
0.237
0.210
0.139
0.171
0.193
0.169
0.189
0.170
0.203
0.180
0.182
O.Z02
0.195
0.170
0.182
0.177
0.170
0.166
0.224
0.202
0.218
0.167
0.235
0.203
0.195
0.175
0.418
0.423
0.406
0.428
0.381
1.087
0.418
0.366
0.429
0.377
0.355
0.365
0.389
0.385
0.418
0.390
0.380
0.375
na
0.436
O.t32
0.3S4
0.462
0.369
0.409
0.393
0.421
0.464
0.467
0.423
0.413
0.338
0.416
0.458
0.398
0.401
0.388
0.348
0.437
0.340
0.395
0.430
na
Q. 489
0.428
0.332
0.436
0.365
0.444
0.402
0.363
0.381
0.410
0.435
0.464
0.406
0.376
0.380
na
3.416
0.441
J.418
0.452
0.383
0.424
0.424
0.441
0.443
0.485
0.468
0.455
0.347
0.434
0.476
0.426
0.415
0.402
0.360
0.479
0.338
D-96
-------
Study No. 5221.07
SUBCHSON1C TOXIC1TY OF META-CRESOL IN SPRACUE DAUIEY RATS
RELATIVE FEHALE ORGAH WEIGHT DATA (X Terminal Body Weight)
[Terminal Sacrifice]
ANIMAL NO. OVA8Y-LFT OVARY-RT ADRENALS BRAIN THf./PARA.
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
355T
3558
3559
3560
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
3581
3582
3583
3584 '
35B5
3586
3587
358B
3589
3590
0.020
0.031
0.033
0.019
0.033
0.023
0.031
0.027
0.029
0.028
0,026
0.020
0.025
0.027
0.035
0.025
0.025
0.026
0.027
0.029
0.032
0.044
0.027
0.027
0.029
0.030
0.034
0.035
0.027
0.041
0.026
0.024
0.044
0.039
0.027
0.029
0.044
0.040
0.034
0.034
0.027
0.039
0.035
0.021
0.034
0,027
0.026
0.025
0.032
0.027
0,023
0.024
0.025
0.031
0.033
0.029
0.024
0.024
0.022
0.024
0.020
0.035
0.024
0.031
0.021
0.023
0.032
0.031
0.038
0.042
0.026
0.028
0.037
0.038
0.022
0.028 '
0.041
0.030
0.023
0.036
0.023
0.035
0.035
0.028
0.040
0.029
0.027
0.027
0.029
0.028
0,016
0.016
0.015
Q.C26
0.035
0.029
0.027
0.030
0.012
0.029
0.039
0.033
0.023
0.029
0.026
0.032
0.023
Q.029
0.029
0.033
0.032
0.025
0.029
0.02S
0.023
0.026
0.041
0.041
0.019
0.039
0.718
0.906
0.782
0.784
0.800
0.721
0.795
0.720
0.800
0.756
0.734
0.685
0.636
0.742
0.833
0.746
0.772
0.780
0.812
Q.863
0.804
0.752
0.713
0.759
o.?aa
0.758
0.774
0.735
0.774
0.761
0.844
0,803
0,859
0.688
0.769
0.879
0.763
0.791
0.730
0.893
Q.022
0.010
0.014
0.012
0.011
0.009
0.007
0.007
0.008
0.005
0.008
0.010
0.008
0,009
0.007
0,010
0.009
0.009
0.012
o.ooa
0.007
0.013
0.009
0.012
0.012
0.012
0.013
0.027
0.006
0.012
0.008
0.007
0.012
0.010
0.007
0.006
0.012
0.011
0.011
0.014
D-97
300
-------
Study No. 5221.07
SUBCHRONIC TOXIcm OF META-CRESOL IN SPRAGUE DAWLEY RATS
RELATIVE FEMALE ORGAN WEIGHT DATA (X Terminal Body Weight)
ITermmal Sacrifice]
ANIMAL NO. OVARY-LFT OVARY-RT ADRENALS BRAIN THY./PARA.
DOSE LEVEL
150 mg/kg/day
450 mg/kg/day,
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3648
3649
3650
O.OZ5
0.033
0.026
0.048
0.030
0.020
0.051
0.022
0.050
0.022
0.031
0.024
0.034
0.018
0.025
0.025
0.014
0.028
C-.050
0.031
0.030
0.023
0.034
0.030
0.035
0.027
0.030
0.027
0.026
0.028
0.030
0.022
0.032
0.028
0.035
0.026
0.055
0.031
0.021
C.019
0.027
0.027
0.028
0.032
0.032
0.039
0.041
0.021
0.043
0.027
0.025
0.028
0.031
0.023
0.028
0.033
0.020
0.031
0.045
0.027
0.030
0.024
0.042
0.038
0.042
0.033
a. 037
0.023
0.020
0.031
0.027
0.023
0.045
0.032
0.031
0.024
0.054
0,025
0.016
0.025
0.026
0.032
0.036
0.033
0.028
0.032
0.032
0.023
0.027
0.035
0.020
0.028
0.028
0.026
0.016
0.025
0,020
0.029
0.039
0.026
0.031
0.023
0.024
0.027
0.033
0.026
0.027
0.032
0.040
0.029
0.025
0.019
0.026
0.036
0.012
0.023
0.039
0.023
0.028
0.026
0.749
0.746
0.810
0.846
0.813
0.791
0.802
0.646
0.737
0.811
0.661
0.706
0.743
0.767
0.858
0.738
0.647
0.829
0.843
0.831
0.873
0.758
0.918
0.731
0.864
0.723
0.833
0.830
0.993
0.359
0.823
0.592
0.873
0.984
0.765
0.835
0.748
0.694
0.699
0.685
0.009
0.013
0.011
0.009
0.013
0.010
0.012
0.011
0.011
0.011
0.009
0.011
0.008
0.006
0.010
0.011
0.009
0.008
0.009
0.007
0.013
0.011
0.008
0.010
0.009
0,010
0.010
0.006
0.015
0.013
0.009
0.006
0.009
0.014
0.012
0.007
0.012
0.006
0.008
0.012
D-98
201
-------
Study No. 5221.07
SUBCHRCMIC TCXICITY OF META-CRESOL IN SPRAGUE DAULET RATS
MALE URIHALYSI5 DATA
[Interim Sacrifice]
Animal no. App. Vol. 1.035
1.015
>1.035
1.027
1.028
1.026
1.031
1.029
>1.035
1.017
>1.035
1.025
M.035
1.018
>1.035
1.017
>1.035
1.016
1.013
1.013
1.030
1.014
1.025
1.014
1.011
1.010
1.016
1.016
>1.035
1.014
1.016
1.011
1.017
. 1.016
>1.D35
1.012
1.010
1.031
y
dy
y
y
y
y
y
y
y
y
y
dy
y
dy
• y
y
y
y
y
y
y
y
y
y
y
iy
iy
y
y
a
iy
y
Ly
y
y
dy
iy
iy
y
a.o
6.0
8.0
6.0
a.o
8.0
7.0
7.0
8.0
6.0
8.0
7.0
8.0
8.0
8.0
7.0
8.0
7.0
8.0
8.0
7.0
9.0
8.0
7.0
8.0
8.0
8.0
a.o
8.0
5.0
8.0
7.0
a.o
8.0
7.0
8.0
8.0
8.0
6.0
1 +
2+
n
1+
1+
tr
1 +
1+
1+
1+
tr
1+
1 +
1 +
1+
2+
1 +
1 +
1*
tr
tr
1 +
1 +
1 +
tr
n
1 +
n
n
1*
1 +
tr
1+
1 +
1+
1+
tr
tr
n
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
tr
1 +
tr
1 +
1 +
tr
1 +
tr
tr
1+
tr
1+
1 +
1 +
1+
2+
1 +
1 +
n
tr
n
tr
tr
1*
tr
n
tr
1 +
n
2+
n
tr
n
1+
tr
tr
tr
tr
tr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
. "3
ng
ng
ng
ng
ng
ng
ng
1+
ng
ng
ng
ng
. ng
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
rg
ng
ng
ng
ng
D-99
*>: A <•">•
/i U 6
-------
Study Mo. 5221.07
SUBCHRON1C TOXICITr OF META-CRESOL IN SPRAGUE DAWLEY RATS
HALE MICROSCOPIC UR1NALYSIS DATA
[Interim Sacrifice]
Animal no. R8C/HPF WBC/HPF EPI/HPF CASTS/LPF CRYSTALS XEAST BACTERIA
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
3401
3402
3403
3404
3405
3406
3407
3403
3409
3431
3432
3433
3434
3435
3436
3437
3433
3439
3440
3461
3462
3463
3464
3465
3466
3467
3463
3469
3470
3491
3492
3493
3494
3495
3496
3497
349S
3499
3500
0
1-2
0
0
0
0
0
0
0-1
0
0
0-1
0-1
0
0
0
0
0
0-1
0
0
0
0
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0
0
2-3
0
0
0
0
0
0
0
0
1-2
0
0
0-1
0-1
0
0
0
0
1-2
0
0
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0
0
0
0
0
2-3
0
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0 '
0
0
0
0
tp\co
CO
tp
CO
tp\co
rv
n
CO
tp
n
tp
CO
tp
tp
n
n
tp
tp
tp
tp
CO
tP
tp
CO
tp
tp
tp
tp
tp
n
tP
CO
tp
tp
CO
CO
tp
tp
CO
n
n
n
n •
m
n
n
n
n
n
n
n
n
n
n
n
n
n
f
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
m
f
f
num
num
m
f
m
nun
f
m
m
m
num
f
f
m
f
num
num
num
m
m
num
f
f
m
m
mum
m
num
m
nurn
nun
num
m
m
m
f
D-100
-------
Study No, 5221.07
SU8CHRONIC TOXICITY OF META-CRESQl IN SPRAGUE DAUIEY RATS
MALE tlRINALYSIS DATA
[Terminal Sacrifice]
Animal no. App. Vol. (rolj Sp. Gr. Color pH Protein Glucose Ketones Uro. Bili. Blood Hgb.
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3441
3442
3443
3444
3445
3446
3447
3443
3449
3450
3471
3472
3473
3474
3475
3476
3477 :
3478
3479
3480
3501
3502
3503
3505
3506
3507
3508
3509
3510
3519
el
c
hz
cl
cl
cl
hz
cl
hz
el
el
cl
cl
cl
cl
el
hz
cl
hz
cl
cl
cl
cl
cl
cl
hz
cl
hz
cl
hz
c
cl
cl
cl
c
hz
cl
cL
hz
hz
11
9
12
15
- 13
15
14
15
15
14
13
13
10
14
15
13
12
15
14
14
15
14
14
14
15
15
14
14
15
14
13
15
15
15
15 '
13
14
13
14
14
>1.035
1.034
1,017
1.025
>1.035
1.012
1.017
1.028
1.023
1.017
1.027
1.033
1.032
1.027
1.025
1.029
1.013
1.030
1.022
1.021
1.025
1.017
1.023
> 1.035 '
1.013
1.015
1.030
1.022
1.026
1.011
1.034
>1.035
1.017
1.020
1.024
1.010
1.014
1.019
1.019
1.015
a
y
s
y
y
y
y
y
s
y
y
y
y
y
s
y
s
s
y
y
y
s
s
a
y
s
y
y
s
s
y
y
s
y
y
s
s
s
s
s
9.0
6.0
7.5
7.0
9.0
9.0
9.0
5.S
6.5
9.0
9.0
8.0
8.5
9.0
7.5
9.0
7.5
8.5
9.0
9.0
8.0
9.0
9.0
7.5
9.0
7.5
8.0
8.0
8.0
9.0
5.5
5.5
7.0
9.0
6.0
9.0
8.0
7.5
7.0
9.0
8
1+
tr
tr
1+
tr
tr
1+
1 +
tr
tr
1 +
1*
1*
tr
1*
tr
tr
1 +
tr
tr
tr
tr
tr
tr
tr
1+
tr
1+
tr
tr
tr
tr
tr
ng
tr
tr
tr
tr
tr
1 +
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
na
ns
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
nr
ng
1+
ng
ng
ng
ng
1+
ng
nr
ng
ng
ng
1+
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
"9
ng
ng
ng
ng •
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
«g
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
10ery\ul
ng
ng
ng
ng
ns
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
50ery\ul
ng
ng
ng
50ery\ul
ng
ng
ng
ng
rtg
ng
ng
ng
ng
ng
ng
D-101
*~"i
•
-------
Study No, 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE DAULET RATS
HALE MICROSCOPIC URIHALYSIS DATA
ITerminal Sacrifice]
Animal no. RBC/HPF WBC/HPF EPI/HPF CASTS/LPF CRYSTALS YEAST BACTERIA
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
150 mg/kg/day
450 mg/kg/day
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3441
3442
3443
3444
3445
3446
3447
344S
3449
3450
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3501
3502
3503
3505
3506
3507
350S
3509
3510
3519
0
0
0
0-1
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0
0
0
0
0
0-1
0
0-1
0
0
0
0
0-1
0
0
0-1
0
0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0-1
0
0
0
0
a
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.
0
0
0
0
0
0
0
0
0
0
a
0
0
0
0
0
0
0
0
0
0
0
tp
tp\co
n
co\tp
tp
tp
tp
CO
CO
tp
tp
tp
tp
tp
tp
tp
tp
••)
tp
tp
co\tp
tp
tp
n
tp
tp
tp
tp
tp
tp
co\tp
CO
CO
tp
n
tp
tp
n
CO
tp
m
n
n
n
n
f
n
n
n
n
n
f
f
n
f
n
n
m
n
n
f
n
n
n
f
f
f
n
f
f
f
f
n
n
n
n
f
m
rt
n
n
n
f
m
m
m
m
f
m
n
m
n
m
m
m
m
m
n
m
m
m
m
m
m
n
m
m
m
n
m
f
m
m
m
f
f
m
nun
m
m
D-102
£05
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE DAULEY RATS
FEMALE URINALYSIS DATA
[Interim Sacrifice]
Animal no. App. Vol. 1.035
1.017
1.035
1.020
1.027
1.009
1.025
1.018
1.023
1.031
1.013
1.019
1.019
1.023
1.010
1.030
1.032
1.030
1.030
1.013
1.016
1.018
1.017
1.020
1.031
1.014
1.025
1.016
>1.035
1.012
1.017
1.025
1.015
1.031
>1.035
1.028
1.016
1.015
1.021
1.011
y
y
y
y
Y
ly
y
y
y
y
y
y
y
y
y
y
Y
y
y
Y
y
y
y
y
y
y
y
y
hz
y
y
y
y
y
y
y
y
y
y
y
7.0
8.0
3.0
3.0
9.0
8.0
9.0
7.0
a.o
3.0
8.0
8.0
7.0
7.0
7.0
8.0
7.0
7.0
7.0
8.0
a.o
8.0
7.0
7.0
6.0
7.0
7.0
8.0
7.0
8.0
7.0
7.0
7.0
7.0
6.0
8.0
9.0
7.0
7.0
7.0
1+
1+
tr
n
1+
tr
1 +
tr
1+
1 +
tr
tr
1 +
tr
n
1+
1 +
n
1 +
n
t
1+
n
1+
1+
n
n
tr
1+
tr
n
n
tr
1+
tr
1+
1+
n
1+
tr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
1+
n
tr
n
tr
n
tr
tr
n
n
n
n
n
tr
n
1+
1 +
tr
1+
n
n
n
n
tr
tr
n
n
n
tr
n
n
n
n
1+
tr
tr
n
n
tr
n
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
1+
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
tr
ng
ng
ng
3+
ng
ng
i +
ng
D-103
206
-------
Study No. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE OAWLEY RATS
FEMALE URINALYS1S DATA
[Terminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
Animal no. App. Vol. (ml) Sp. Gr. Color pH Protein Glucose Ketones Uro, Bili. Blood Hgb.
50 mg/kg/day
150 mg/kg/day
450 mgAg/day
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
3601
3602
3603
3604
3605
3606
3607
3603
3609
3610
3631
3632
3633
3634
3635
3636
3637
3638
3«39
3640
hz
cl
hz
cl
c
cl
c
cl
hz
cl
cl
cl
cl
cl
cl
cl
hz
cl
cl
c
hz
c
cl
hi
hz
hz
e '
cl
hz
hz
hz
hz
cl
c
hz
hz
hz
c
hz
cl
14
14
7
14
15
7
10
14
5
4
14
13
15
7
15
12
15
12
9
12
14
14
14
11
14
15
14
15
4
12
10
15
14
10
13
15
14
15
14
15
1.021
1.020
1.034
1.021
1.015
1.023
1.027
1.020
>1.035
>1.035
1.018
1.019
1.020
1.020
1.016
1.018
1.015
1.024
1.025
1.018
1.014
1.023
1.017
1.018
1.012
1.015
1.011
1.023
>1.035
1.020
>1.035
1.021
1.020
>1.035
1.023
1.015
1.010
1.018
1.015
1.015
y
s
y
y
y
y
y
y
y
y
y
s
y
s
s
y
py
y
a
s
s
y
y
s
s
s
s
s
y
s
y
y
y
y
y
y
s
y
s
y
9.0
9.0
9.0
9.0
6.5
9.0
6.0
9.0
7.0
9.0
8.0
8.0
9.0
8.0
9.0
9.0
9.0
7.0
9.0
8.0
6.5
6.0
9.0
6.5
7.5
7.0
6.5
9.0
7.0
7.0
6.0
5.5
8.0
6.0
9.0
9.0
7.0
6.0
7.5
6.5
tr
tr
tr
ng
tr
1+
tr
tr
tr
1+
tr
tr
tr
ng
tr
tr
tr
tr
tr
nun
ng
tr
tr
tr
tr
ng
ng
tr
tr
ng
tr
tr
tr
tr
tr
ng
ng
tr
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
1 +
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
1-f
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
D-104
7
-------
Study No. 5221.07
Subchronic Toxicity Study of
Meta-Cresol in Sprague Dawley Rats
Female Urinalysis
Interim Sacrifice
ANIMAL
RBC/HPF WBC/HPF EPI/HPF CASTS/LPF CRYSTALS YEAST BACTERIA
0 ng/kg/day
3531
' 3532
3533
3534
3535
3536
3537
3538
3539
3540
50
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
150
3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
0
0
0
0
0
0
0
0
0
0
rog/kg/day
0
0
0
o .
0
0
0
0-1
0
0
mg/kg/<3ay
0
0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
TP,CO
TP
TP
TP
TP
TP
TP
CO
NONE
NDA
TP
TP
TP,QO
TP,CQ
NONE
NONE
DO
CO
TP
TP
NONE
TP
NONE
00
CO,TP
TP,CP
NONE
TP
CO
TP
NONE
NONE
NONE
NDA.
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NDA •
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NDA
NONE
NONE
NONE
NONE
NUM
MANY
FEW
FEW
NUM
MANY
NUM
MANY
FEW
FEW
MANY
FEW
NUM
NUM
MANY
NUM
FEW
FEW
FEW
NUM
MANY
NUM
FEW
NUM
FEW
FEW
FEW
MANY
MANY
MANY
Abbreviations used:
TP = Triple Phosphate, CO = Calcium Oxalate
NDA = No Data Available, NUM = Numerous
D-105
*> 0 8
f'*. \Jf LJ
-------
Study No. 5221.07
Subchronic Toxicity Study of
Meta-Cresol in Sprague Dawley Eats
Female Urinalysis
Interim Sacrifice
ANIMAL
450
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
RBC/HPF
ng/Kg/da:
0
0
0-1 .
0
0
0
0
0
0
0
WBC/HPF
f
0
0
0
0
0
0
0
0
0
0
EPI/HPF
0
0
0
0
0
0
0-1
0
0
0
CASTS/LFF
0
0
0
0
0
0
0
0
0
0
CRYSTALS
CO
NONE
CO
CO,TP
CO,TP
TP
TP
CO
TP
NONE
YEAST
NONE
NONE
FEW
NONE
NONE
NONE
NONE
NONE
NONE
NONE
BACTERIA
NUM
MANY
NUM
NUM
MANY
MANY
MANY
NUM
MANY
MANY
Abbreviations used: ' TP = Triple Phosphate, CO = Calcium Oxalate
NDA ~ No Data Available, NUM — Numerous
D-106
09
-------
Study No. 5221.07
Subchronic Toxicity Study of
Meta-Cresol in Sprague Dawley Rats
Female Urinalysis
Terminal Sacrifice
ANIMAL RBC/HPF WBC/HPF EPI/HPF CASTS/LPF CRYSTALS YEAST BACTERIA
0 ing/kg /day
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
50
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
150
3601
3602
3603
36C4
3605
3606
3607
3608
3609
3610
0
0 .
0
0
0-1
0
0
0
0
0
mg/kg /day
0
0
0
0
0
0
0
0
0
0-1
mg/kg/day
0-1
0
0
0
0
0
0
0
0
0
Abbreviations used: TP =
NDA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
= Triple
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Phosphate,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
TP
TP
TP
TP
NONE
TP
TP,CO
TP
TP
NONE
TP
TP
TP
TP
TP
TP
TP
CO,TP
TP
TP
CO,TP
NONE
TP
CO,TP
TP
NONE
NONE
TP
CO
TP
CO = Calcium
= No Data Available,
NONE
NONE
NONE
FEW
NONE
NONE
NONE
FEW
NONE
NONE
NONE
NONE
NONE
FEW
FEW
FEW
FEW
FEW
NONE
NONE
NONE
NONE
FEW
NONE
NONE
NONE
NONE
NONE
NONE
NONE
Oxalate
MANY
MANY
MANY
MANY
FEW
MANY
MANY
MANY
MANY
FEW
MANY
NONE
MANY
MANY
NONE
MANY
FEW
MANY
NONE
FEW
NONE
FEW
MANY
MANY
FEW
MANY
FEW
FEW
MANY
NUM
NUM = Numerous
D-107
210
-------
Study No. 5221.07
Subchronic Toxlcity Study of
Meta-Cresol in Sprague Dawley Rats
Female Urinalysis
Terminal Sacrifice
ANIMAL
RBC/HPF WBC/HPF EPI/HPF CASTS/LPF CRYSTALS YEAST BACTERIA
450 mg/kg/day
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CO
CO
TP
CO
TP
TP
NONE
NONE
CO,TP
CO,TP
FEW
FEW
NONE
NONE
MANY
FEW
NONE
NONE
NONE
NONE
NONE
FEW
MANY
FEW
MANY
NONE
FEW
FEW
FEW
MANY
Abbreviations used:
TP = Triple Phosphate, CO = Calcium Oxalate
NDA - No Data Available, MUM = Numerous
D-108
-s
JL
-------
Final Report
Study No. 5221.07
APPENDIX E
OPHTHALMOLOGY REPORT
E-l
-------
Study No. 5221.07
SUBCHRQNIC TOXXCTIY OF MEm-CRESOL
IN SH&GUE DAWLEY RMS
ABBREVIATION CODES
lyeExaminations
nvl = no visible lesions
dead = unscheduled death
A = os (left eye) focal zone of retinal degeneration
ph = persistent hyaloid
na - ophthalmology exam not applicable? animal removed
at interim sacrifice
*>
-------
Nancy M. Bromberg, V.M.D., M.S.
Diplcmate, American College of Veterinary Ophthalmologists
4105 Brandywine Street, Northwest
Washington, D.C. 20016
202/363-7303
- c"i i N re
F O R • A N I M A I S
September 3, 1986
Barry S. Levine , D.Sc, DABT
Microbiological Associates
5221 River Road
Bethesda, MD 20816
SUBJECT: Revised Report - Ophthalmoscopic Examination of Rats
Study 5221.07 December 30, 1986
Pretest examinations on October 2, 1985 showed three male rats to have
persistent hyaloid remnants (3401 left eye, 3431 left eye, 3432 right eye).
PH is a common developmental finding in young rats. The presence of PH does
not cause exclusion of the animal from a study.
At terminal examination on December 30, 1985, all animal,1? were found
to have no visible lesion except:
Rat 3583, female Group II - zone of retinal degeneration in left eye.
Due to the singular occurrence of this abnormality, I do not consider it
to be compound related.
rf....... I .:— ,
Naticy 5JN Bi uuiuci-g,,
Dipiomate/ A.C.V.O.
omberg, V.M.E&/M.S.
E-3
^ -i fl,
^ 1 4
-------
SUBCHRON1C TOX1CITY Of META-CRESOL IN SPRAGUE DAWLEY RATS
MALI EYE EXAMINATIONS
Animal no. PRETEST-Slght Eya PRETEST-Left Eye TERMlNAL-Right iye TERHINAL-Left Eye
DOSE LEVEL
0 ing/kg/day
50 mg/kg/day
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
3431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
ph
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
ph
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
ph
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
HVl
nvl
nvl
rvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
1-4
?15
-------
SUBCHRONIC TOX1CITY OF META-CRESCl IN SPRAGUE DAWLET RATS
MALE EYE EXAMINATIONS
Aniral no. PRETEST-Right Eye PRETEST-lef: Eye TERMINAL-Right Eye TERMINAL-Left Eye
DOSE LEVEL
50 mg/kg/day 3447
(continued) 3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3453
3459
3460
ISO mg/kg/day 3461
' 3462
3463
3464
3465
3466
3467
3463
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3431
3482
3483
3484
3485
3486
3487
34S8
3489
3490
nvL
nvL
nvl
nvL
nvl
rtvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvi
nvl
nvl
, nvl
nvl
nvl
nvL
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt •
nvl
nvl
nvl
nvl
nvl
rwl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
. nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
E-5
216
-------
SUBCHRONIC TOXICITT Of META-CRESOL IN SPRAGUE DAWLSY SATS
MALE EYE EXAMINATIONS
Animal no. PRETEST-Right Eye PRETEST-Le-ft Eye TERMlNAL-High: Eye TERKIKAL-Lefc Eye
DOSE LEVEL
450 mg/kg/day
3491
3492
3493
3494
3495
3496
3497
3493
3499
3500
3501
3502
3503
3504
3505
3506
3507
3505
3509
3510
3511
3512
3513
3514
3515
3516
3517
3513
3519
3520
nvl
nvL
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvL
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvL
nvl
dead
rvvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
dead
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
*?
E-6 "'
-------
SUSCHRONIC TOXICin Of HETA-CRESQt IH SFRAGUE OftytEY RATS
FEMALE EYE EXAMINATIONS
Animal no. PRETEST-Right lye PRETEST-Left Eye TERMINAL-Right iye TERMlNAL-left Eye
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
353 1
3332
3533
3534
3535
3536
3537
3538
3539
3540
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3571
3572
3573
3574
3575
3576
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
.nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvi
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
E-7
IS
-------
SUBCHRONIC TOXICITY OF META-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE EYE EXAMINATIONS
Animal no. PRETEST-Right Eye PRETEST-Left Eye TERMINAL-Right Eye TERMINAL-Left Eye
50 mg/kg/day 3577
(continued) 3578
3579
3580
3581
3562
3583
3564
3525
3586
3587
3583
3589
3590
150 mg/kg/day 3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3613
3619
3620
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
A
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
219
E-8
-------
SUBCHRQNIC TOXICITY OF META-CRESOL IN SPRAGUE DAULEY RATS
FEMALE EYE EXAMINATIONS
Animal no. PRETEST-Right Eye PRETEST-Left Eye TERMINAL-Right Eye TERMINAL-LefC Eye
DOSE LEVEL
450 mg/lcg/day
3621
3622
3623
3624
3625
3626
3627
3623
3629
3630
3631
3632
3633
3634
3635
3636
3637
3633
3639
3640
3641
3642
3643
3644
3645
3646
3647
3643
3649
36SO
nvl
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
. nvl
nvl
na
ra
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nyl
nvl
nvl
nvl
E-9
-------
Final Report
Study No. 5221.07
APPENDIX F
PMHODDGY REPORT
221
F-l
-------
10075 Tyler Place
Hyatt Park II
Ijamsville, Maryland 21754
(301) 663-l6<*4
Pathology Associates, Inc.
SUBCHRONIC TOX1CITY OF META-CRESOL
IN 5PRAGUE DAWLEY RATS
PREPARED FOR
MICROBIOLOGICAL ASSOCIATES, INC.
9
-------
TABLE OF CONTENTS
PAGE
I. PATHOLGY NARRATIVE 1-1
I!. PROJECT SUMMARY TABLE . 11-1
III. TABULATED ANIMAL DATA 111-1
IV. GROSS VS. MICROSCOPIC FINDINGS
Terminal Sacrifice IV-1
Interim Sacrifice IV-30
V, QUALITY ASSURANCE REPORT V-1
APPENDIX 1 REPORTS CODE TABLE
APPENDIX 2 ABBREVIATION LIST
*i 9 o
-------
1 PATHOLOGY NARRATIVE
-------
10075 Tyler Place
Pathology Associates, Inc. -!?yaS'Pa?CIJ,,-<'
^J Ijamsvtlle. Maryland 21 / 54
(301) 663-1644
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE DAWLEY RATS
INTRODUCTION
This Is the final pathology report by Pathology Associates, inc. (PA!) to
Microbiological Associates, Inc. (MA!) representing support required to
conclude the study designated "Subchronic Toxicity of Meta-Cresol in Sprague
Daw ley Rats" as described in the MAI protocol number 5221,07 dated 26
September 1985.
EXPERIMENTAL DESIGN AND METHODS
Four groups, each consisting of 30 male and 30 female rats were given
0, 50, 150 or 450 mg/kg body weight of meta-cresol in corn oil per day by
gavage. Ten males and ten females (selected prior to the initiation of the
study) from each group were sacrificed and necropsied during test week
seven. At the end of 13 weeks of treatment, the remainder of the animals
were sacrificed and necropsied in accordance with the study protocol and
with PAI Standard Operating Procedures, All required tissues from the
terminal sacrifice and the one animal which died prior to sacrifice as well as
all tissues containing gross lesions at the interim and terminal sacrifices
were processed, and slides were prepared for microscopic examination,
GROSS OBSERVATIONS
Gross observations were noted in 1 1 of the 80 rats necropsied at the
interim sacrifice. Findings are presented in the tables on pages IV-30 and
IV-31 including corresponding microscopic observations. All of the lesions
are considered' to be incidental.
At the terminal sacrifice, gross observations were found in all dose
groups. All of the observations are considered incidental and are presented
in the Gross vs. Microscopic Tables.
1-1
-------
HISTOPATHOLQ6Y
All available required tissues in the 0 mg/kg and 450 mg/kg'terminal
sacrifice dose groups, all required tissues from the early death animal
(*3504) and all tissues having gross lesions noted at the interim and
terminal sacrifices were examined microscopically. Microscopic findings for
Individual animals are presented by dose/sex group in the Tabulated Animal
Data Tables, The left-hand margin lists only those lesions which were found
in that dose group. Abbreviations for entries used in these tables are
explained in the Reports Code Table in Appendix 1. Microscopic findings for
all groups necropsied at terminal sacrifice are summarized by sex on the
Project Summary Tables,
No neoplasms or dose-related lesions were present. Numerous
incidental lesions were present in both the 0 mg/kg and 450 mg/kg dose
groups, Lymphoid hyperplasia was present in the mandibular lymph nodes of
17/20 and 18/20 vehicle control and high dose males respectively and 13/20
and 18/20 vehicle control and high dose females respectively. Perivascular
lymphocytic infiltrate was present in the lungs of 17/20 male and 17/20
female vehicle control rats and 10/20 male and 13/20 female high dose rats.
Accompanying this'perivascsular infiltrate was an interstitial inflammation
in 5/20 male and 6/20 female controls and 4/20 male and 3/20 female high
dose rats.
Other incidental lesions included embryonal duct cysts in both males
and females, chronic myocardial inflammation in the hearts of males,
degenerative kidney changes in males and females, and developmental,
inflammatory or degenerative changes in the liver, testes, prostate or uterus.
These findings occurred in small numbers divided approximately equally
between high dose and control animals, and will not be discussed further.
DISCUSSION
Animal No. 3504 was the only animal found dead during the study, At
necropsy, the lungs were red, and blood was present in the thoracic cavity,
Lung congestion was present microscopically, but no cause of death was
determined, although gavage error was considered possible.
1-2
-------
Lymphoid hyperplasia in the mandibular lymph nodes of both male and
female rats occurred with similar frequency in both the vehicle control and
high dose groups. Changes consisted of numerous prominent germinal centers
in the cortex surrounding large numbers of plasma cells in the medullary
areas of the nodes. The changes represent a relatively localized immune
stimulation of unknown etiology.
Inflammatory changes in the lungs of male and female rats from both
vehicle control and high dose groups suggest infection from an adventitious
microbia! agent,
CONCLUSION
Under the conditions of this study, meta-cresol was not found to cause
any chemical-related lesions.
Lucas H. Brennecke, O.V.M.
Diplomate, A.C.V.P.
20 March 1986
1-3
-------
II PROJECT SUMMARY TABLE
^ 9
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.87
SU8CHRDN1C TSJXICITf OF HETA-S8ESOI
IH SPMSOE-MWLET RrtTS
Proj e
ct Summar
y Tabl e
StfmRY : Incidence of NEOPLAST1C and N3H€OPWSTI
P80JECT ID. NO: HCfiESOL
MYS-, ALL
68QUP:
HMBS1 OF /WfttlS:
I8AIN
HEHORRWGS
SCIATIC NEWE
SP!»L MM
... 8CKE'
Btt€ MARRQU
SALIVAS EUW
MW18ULAS LWPH NODE
fffPERPWSlA, LW«OIO
wmus
H£«ORR»OE
iwcRas
HOlQfiRWSE
INFUWttTlCH, CHRONIC
PITUITARY
tfST, PAK IMTEiJMEDIA
CYTCPlASrilC WUO.,PARS OI5T
FATES: ALL
S£X: WiLE
fiNG/Ke . 50HB/K6
20
1
1 Ex 29
1!
i Ex 20
1 h 20
i Es 20
i Ei 2fl
I E* 20
i Ei 20
i?
i EJ 20
4
Ik 20
(I
3
1 EJ 17
8
D
9
,
0
11
a
0
8
S
9
a
Q
0
0
1)
g
g
0
0
9
C Microscopic
ISOMS/KB
4
1
D
0
0
0
0
0
0
a
0
0
8
Q
0
3
D
0
0
Findings
45SWXS
20
1
21
1
21!
21
21
20
25
20
IS
20
5
28
I
8
If
3
I
(Report Continued)
II-l
-------
PATHOLOGY ASSOCIATES, IMC.
STUDY NO, 522!.(t?
StUCHRBNIC TOXICITY OF HETA-CREiOL
IN SPiMGUE-DAWLEY RATS
Project Summary Table
StMfcRYs Incidence of NEflPLASTlC and NON-NEOPLASTIC tlitroscopic
PROJECT 13. NO: MCRESOL
DAYS! ALL
SRflUP;
NUMBER OF ANIHflLS:
TOTSDIB
• BliRYINAL DUCT CfST
ATROPHY
LYMPHOCYTIC INrlLTfMTE
mmm,
TRACHEA
ESflPWGUS
ABREML SLANO
LlflS
CON6E5THN
LWHOCYTIC INFILTBVTE.PERW
JHTERSTIT3AL INFl/mmON
mm
1NFUH., CHRONIC, MYQKR03U1
AORTA
03LCN
DUQDBflK
FORE5TOMACH
GLANBULAS STDWCH
FATES:
SEXi MALE
OHG/K5
2D
1
I Ex 20
3
0
I
1 Ei 12
i Es 20
t E: 20
,<.»
1 Ex 20
8
17
5
1 Ex 20
7
1 Ex !?
1 Ex 20
1 E: 20
1 Ex 20
1 Ex 20
ALL
5DWG/KG
t
0
0
1)
0
0
0
0
9
0
0
'o
B
J
9
0
0
0
0
D
ISOHS^KS
4
1
0
O
a
0
0
t
t
8
0
0
0
0
0
i
0 •
0
0
0
0
Findings
20
i
if
!
0
14
20
>
20
29
1
id
28
7
29
2D
1?
1?
a »? o A
II-2
-------
PATHOLOGY ASSOCIATES, INC,
STUDY NO, 5221.37
•SUBCHRONIC TQX1C1TY OF META-CHESOL
IN SPRA6UI-MMIEY RATS
Proj e
ct Summary Table
StftWRY! Incidence of NEOPLAST1C and NUI-HIOPWSTIC Microscopic Findings
PRDJECT ID. NO: HMESOL
MYS! ALL
mwf:
NU18ER OF tfilMSr
SKIN
»««Rf 6UW
SKELETAL NUSCIE
IMS
HEMTODIAPHftWHATIC NOBULE
>-?"• HMOTPQIETIC CELL PROL1F.
LWHCCYT1C JNFILTWTE
CnOPlftSMIC WiGJQlAT3CN
MEC!?OS1S
««
KIDNEY
LWPHCCniC INFILTRATE
NEPWOPATUr
RE6WEWTION, 8BW. TUMILIS
CYfT
URIIMRY BLADDER ,
TISTE5
ATROPKfjSEMlNlFclOUS TUBULES
PSOSTAT1
IWPHOCtTIC INFILTfMTE
FATES:
SEXi HflLE
OMfi/KG
20
i
t Ex 20
1 Ex 12
1 E* 28
1 Ex 20
a
i
0
^
1
1 E: 20
i Ex 20
9
7
0
i
1 Ex 20
I Ex 20
i
I Ex M
3
ALL
sms/KS
*
t
a
g
0
7
0
a
j
2
1
9
2
3
2
a
a
0
3
3
0
J
1SOMS/KS
4
1
g
8
0
3
0
0
0
2
0
G
a
9
1
S
0
g
i
i
0
0
45Wi/Kf
23
i
211
12
20
20
I
0
J
0
8
a
21
j^nJe^j'"""""""""'^
j**" ™~S» J
^
9
21
21
S
28
3
TORIES • I Ex I
11-3 ^ O
J.
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO, 3221,0?
StliPffiQNIC TOXIClTf OF HETA-CRBfll
IN SPMBUE-WULEY PATS
Project Sumrnarx Table
i Sncidjuce o* NEOPLAST1C and NCN-NEOPLASTIC Microscopic Finding
PROJECT IB. NO: HCRESDL
BAYS; fill
6ROUP-.
MlfiER OF WIWLSi
WTIS: flU
SIX:
«E/K3 50K6/K5 150MG/KG 45CMS/XI
2B > 4 20
UTESUS
1
1 E% 1
KRV1X
f Ei 0
I Ex 19
(Report Caniinued)
O
II-4
-------
PATHOLOGY ASSOCIATES, INC.
STUM NO, 5221.0?
SUiEHIONIC TOXlClTf OF HETA-CRESOl
IN SPWGUE-MULFf iWTS
Project Summary Table
SltfWWs Incidenci of NEOPLASTIC and KCH-flEflPWOTC Microscopic Findings
PROJECT ID.' NO: MCRESOL WTK; AU
MIS: ALL SEXi HW.E
GROUP; W8/K8 3Wa«8 150HS/KS 4SJM6/KS
NU1BE1? OF miWLS: 20 1 4 20
OTHER TISSUES (WO LESI1KS;
*? o o
11-5
-------
PATHOLOGY ASSOCIATES, INC
STUBY KB. 5221,07
SUBCHRtNIC TIKI CITY OF «ETA-€RESflL
1M SPRA6UE-MWLEY RATS
Project Sumrnarx Table
SUWRYi Incidents of NEOPWSTIC snd NCN-NEOPUST1C Hicrwcopic
PROJECT IB. NO; WOOL •
DAYS; ftLL
GSQUP; .
NUH8ER W miWLSi '
flRAW
SCIATIC NEWE
SPINAL CORD
SOME
BONE WOTW
SAUVAIW StfND
WNOIiULAR LYMPH NODE
HTPERPWSW, tWHOIO
THYHUS
mmm
(Cm* KLL ATROPHY
INRJ««TION, OiREWIC
rra,™
TWR01D
KSiTfUWL DUCT CfJT
MRATHYHOID
FflTES: ftll
SEX; FOWIE
WE/KS SDHO/Ka
20 2
1
1 Ei 211
i Et 20
i Ex 20
1 Ex 20
1 Ex 20
1 Ex 20
« Ex 20
13
1 Ex 20
9
i Ex 20
1
I
t Ex 20
1 Ei 2D
3
1 b 13
II-6
f
Q
8
0
1
D
9
0
Q
0
0
0
0
0
0
9
0'
I55MS/KG
2
1
0
0
0
0
0
i
0
0
e
8
0
0
8
0
a
0
0
Findings
2B
i
211
20
25
20
29
2B
a
13
21
3
23
a
1
»
2!
13
4"*s *•"•& ^
Depart Continuid)
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221.0?
SUSCHRENIC TOXlCm OF META-CRESfl.
IN SPRAGOE-WULEY RATS
Project Summary Table
StttWWs Incidence si NEOPWSTIC aad NDN-NEQPlASTIC Microscopic Findings
PROJECT ID, NO: HCRISOL FATES: All
MYS: ALL SEX: FBW.E
GROUP; QHS/KS
NWiER OF AN1WLS; 20
t
TRACHEA ' I Ex 20
ESOMW8US 1 Ex 20
ADREWl SUWO . I Ex 20
UNS 1 Ex 20
,;--- LWHOCYTIC INFILTSATl.PERW 1?
:r" INTERSTITIAL INFUWMTlflN iS
HEASfT I Ex 20
AORTA , 1 Ex 20
CCLtN I Ex 20
METAZCW* PARASITE 1
DOQ9EH1M 1 It 20
F3RISTDHACH 1 & 20
SflUWOJJS CfST 0
5UWBUWR STTOCH 1 Ex 2B
SKIN ' i Ex 28
mrt>m euwo i ES 20
II-7
*ft 4 1* 4, "
SIHG/KQ
2
i
0
D
0
0
0
3
1!
8
0
0
11
(1
0
0
1)
1!
0
ji
15IM6/KS
2
I
0
0
0
9
3
3
3
D
0
0
0
0
0
0
0
0
0
45QHG/KE
28
i
23
20
20
20
13
3
!
23
ffl
20
1
21
2
1
21
20
29
235.
-------
PATHOLOGY ASSOCIATES, INC.
STUOYNQ. 5221.37
StliCHRDNIC TCXICm Of HETfl-CRESCl
IH SPWEUE-DAtfLEY MTS
Proj •
c t Summary Tab! e
SUfftRT: Incidence erf NEOPUST1C and NCN-NEOPLASTIC Hicroscopic Findings
PROJECT IS. NO; MCSISOL
DAYS; ALL
SIOUP;
MJMBER CF ANJHflLS:
SKELETAL MUSCLE
IMS
KEPflTODIAPHfWGHATlC NODUIE
iNFLfimttlJN
HBWOPOIETIC CELL PROL1F."
lYKPMCYTlC INFILTRATE
FATTY CWWGE
•?f SPLEEN
KIJMY
LWPHQCYT1C INFILTRATE
NEPHRQMTHY
8£ GENERATION, REKSL TUiULES
HtOR«E?HROSIS, LN1LATBAL
KSI
UR2WRY SLABBER
TiSTIS
PBISTATE
mum
UTERUS
DILATATION
CEWIX
FATES:
SEX: FEmLE
OMB/KS
2(1
1
1 Ex 20
1 El 20
0
1
1
4
0
1 Ex 20
1 Ex 20
S
i
0
3
0
i Ex 2(1
1 Ex 0
1 Ex 8 -
1 Ex 20
1 Ex 20
2
lEx 23
II-E
ALL
SCMG/KS
2
*
3
0
0
0
0
t
0
t
0
3
3
0
9
a
a
0
3
I.
i
D
a
!
150MS/KG
2
1
0
1
1
3
8
a
0
•
0
0
0
0
B
a
8
0
0
0
9
0
D
4SDN6/X6
20
I
28
20
8
0
3
t
1
20
21
3
Q^
!
P
1
20
3
i
20
21
i
28
236
(Report Continufd)
-------
PATHOLOGY ASSOCIATES, INC.
OTDY NO. 5221.117
SUlCtttNIC TOXICITf DF HEW-CRESOL
IN SPWSUE-WULBf SATS
Project Sufwnar-y Table
SUWWRTi Incidence of NEDPWST1C and NON-NEOPLASTIC Hicroscapic Findings
PROJECT ID. NO: HCRISDL FATIS: fill
MYSi ALL SEX: FBttLE
ilDUP: OMG/KS SW«/K6 150ME/KS 156M6/KI
NUHIER Of IWJWLS; 20 2 2 20
I a i i
EYES ' 1 Ex 20 0 0 20
(Xeport Continued)
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUSCHRCNIC TtWClTY OF HEW-SSESOl
IM SPSftGUE-WJlE? SATS
Project Summary Table
SUtMY: Incidence of NEQPLASTIC and Nm-NEflPWSra Hicroseapic Findings
PROJECT 10, NOi HCRISOL FflTES: flli
MYS: ALL SEXi FEJ«LE
WG/KS 5DN8/KS 150HS/K6 45UH8/KB
OF ANlHftlS: 28 2 2 20
TISSUES m
8 a o
WEDWSTlNflL LN-HEMORRW8E 0 1 0
0 3 I
11-10
o o
=. i O
-------
II TABULATED ANIMAL DATA
q
V
-------
PATHOLOOY ASSOCIATES, INC.
STUDY NO, 522!,07
SUBCHROflC TOXIGITY OF NETA-GRESOl
IN SPMSyE-W4.Ef RATS
Tabulated Animal Data
PROJECT
I
6SOUP: WE/KB SEX: fWLE MS; ALL
FATES! ALL
mm. ID. NO;
BfWSN
3411 3412 34S3 34S4 3415 34U 3417 3418 3419 3420
NNNNNHNNNN
SCIATIC NERVE
mmi mm
BEN£
K3NEWSROU
KNN.HHNNNHN
N N N N N
N H N
NNHNNHNHNH
NNNHKNNNHH
ML1WRY
NNNNNN-NNNN
LWH NODE
HTPERPUSM, LYHPHOID
N N
2 - 3 2 1 3 3 1 -
NHMN
NHNHN
PANCREAS
, CHRtNIC
NNNNN NHN
(2) - - - - - -<23 -
PITUIWRY
HNUNNNNUNH
(Report Co»tmu«d!
III-l
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221.07
SIBCHttNIC 70X1CITT OF MFTA-CSESOL
IN SPRAGUE-BAULEf SA7S
Tabulated Animal Data
PROJECT ID! MCRESOL SiOUP: (TO/KG SEX: WLE DAYS:
M6E 2 FATIS: All
ID, NO; 3411 3412 3413 3414 3415 34Ji 3417 34!S 341? 3420
THYROID N N N N N N N N
B1BWWI DUCT CfST <1> - S3)
LYKPHOCYTIC WFlLTfifiTE (3) -
i^RATHYIOID NUHNUUNNM
NNNNNNNNHH
ESOPMUS NNNNNHKNHM
AOSBW. GU«0 NNHNNHNNNH
IUN8 ' H H
LYMFHOCYTIC INFILTBVTE.PEHW <2) <2> <2> <2> - -52) <2) - <3)
ME8ST1TIAL INFLWttTIlW - - - <2> - - <2> - <2>
HEART N H H N N N
- <2> - <3> -
-------
PATHOLOGY ASSOCIATES, INC.
STUDY HO. 522!.0?
SUBCHIKWIC 70X1C1TY OF HETiKRESDL
IN SPRftSUE-WAEY WTS
Tabulated Animal Data
WOJICT ID: MCSESOL BMUP: WS/KB SEX; WLE
Pftfit 3 WTISi flU.
DAYS: fill
10, NO:
3411 3412 3413 3414 3413 341 iS 3417 3418 341? 3420
HNHNNNNNNN
fiUWUWR
HHNNHNHHNM
SKIN
NNNNHKHHNN
WWttfiY
SKELETAL HUSCLE
NNNNNUNUUH
HHNNH-NNNNN
LIUER
STFOPW311C WCUOWT10N
N HNNNNHH
<2> - <2> .......
SPLEW
NNHN.NNHNNN
KIWiY
NEPHROMTHY
CYST
<25
N N N N N
<2> <2>
BIADDER
NNNNNNNNNH
TESTES
NHHNNNNNKH
(Report Casiinuid)
III-3
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221,0?
SUBCKRONIC TOXiClTf OF HET
IN SPWEOE-MULEY »7S
Tabulated Animal Data
PROJECT ID: HCSHSOL SSOUP: fflfi/KS SEX: HfiLE DAYS: AH
PftBE 4 WTES; ALL
IIS. NU: 3411 3412 34i3 3W 3«5 3414 341? 3418 3419 3423
. NHNNHHNN
LWPHECWC INFILTiWII <2) - - - - • - - - - <3>
(WfiRlES
i * 1 * i i
f 1 1 * * i
J * 1 * * 3
t I I i 1
1 i t I t
1 i * t i
EYES HMNNNKKUHN
(fispurt Continuid)
6"1* ,t r&
-------
PATHOL06Y ASSOCIATES, INC.
STUDY NO. 5221,07
SUICHRCNSC TflXICITf OF HETA-CRESOl
IN SPMSUE-MULEY RATS
Tabulated Animal Oa.ta
PROJECT IDs HC8ESOL GROUP'. W6/KS SIX; NflLS DAYS: All
MS 5 FflTES: ftiL
JO. NO: 3411 34!2 3413 3414 3415 3414 3417 3418 341? 3420
me TISSUES WD
(Report Continued)
244
III-5
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221,07
SLiCHiQNlC TOX1CITY OF META-C8ESOL
IN SPRA6UE-MULEY WTS
Tabulated Animal Data
CT ID; MCRESOL SiOUP: OHS/KS SEX) WLE BAYS: ALL
i FATES! ALL
ID, NO: 3421 3422 3«3 3424 3425 3426 3427 3428 3429 3430
HKHN N N N N N N
SCIATIC NERVE NNNHNNNNNN
CORD NNNNNMHNNK
NNNNNNNNHN
Sf€ HARROU NHNNKNNNNN
GWND NNHNNNNNHN
LWH NODE N
(WPiRPUSW, LWHDID 222-222222
THWUS N N H H H H N
HB10RSIW5E ' ---- <1> (1)
WNCREAS N NHHNNNNN
INFUWfeTION, CHRONIC - <2>
PITU1TAW HHNUNNN.NHN
(S?part Continued)
245
III-6
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SU8CHMN1C TOXlCm OF KiTA-CREBOl
IN SPWWJUE-WJLEY RATS
Tabulated Animal Data
PROJ1CT ID; MCRESOL SlOtlPs 0H6/K3 SEX: MALE DAYS;
MG£ 7 FATES: fill
IB. NO! ' 342! 3422 3423 3124 3425 342:5 342? 3421 341? 3430
TSffROIB N NNHNNNNH
BUCT CYST (23
PflMTHYSOID NNUUUliNNNti
T8ACHK NNHMNHNHNN
ESDPWGUS NHNNNNNNHN
«K?ttL 6U«0 , NHHHNNSHMN
LIW6 N
IWHOOTIC 2NF1LT1MTE,P£R!V <2) <2) <25 <2> <2> <2) <2) - <2)
IMTERST1TIAL INFWffttTlCN <2) - - - - - <2> - -
HEART ! N N N N N N N
INFU^.jCHROTC, MYQCftRDIUH ' <2) - - - (2) - CD
MRTA NNONNHNKNN
CCUH NNNNNHNNHN
OUOOffilfl HNNNNNNNNM
(Report Conlinutd)
246
ITI-7
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO. 3221.07
SUBCHRDN1C TOX1C1TY OF HBA-CRESOl
IN 3WGUE-MULEY RftTS
Tabulated Animal Data
PIOJECT IB; KCSESai 5ROUP: OHS/K6 SEX: WLE MYS: ALL
»5f 8 ' FATES! ALL
ID, HOi 3421 3422 3423 3424 3425 3424 3427 3428 342? 3430
FQ8ESTQWCH NNNNHNMNNM
HmOUWR STWCH NNNNHNHNNH
SKIN NNNNNNNNNN
SWNP UNUUUNUHHN
SKELETAL MUiCLE NNNNNNNNNN
LMR N HNNNN NH
HBMTDPOieiC CELi PS1LIF, <2)
CfTOPLASIlC IAC1JOLATJON <2)
SPLEEN NNNNNNNNNN
KIDNEY N N N N N N
NEPHROMTHt - <2) <2> - - - - <2)
BLADDER NNNNNNNNNN
TESTES NNNHNNN NN
ATiOPKV.SBIlNIFEROUS TUBULIS - (I)
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 522!.§7
SUBCHfflWlC TWIC3TY OF MCTA-C3ESOL
IN SPMGUE-MULFf MTS
Tabulated Aniraal Data
PROJECT ID: HCIE50L 6ROUP:'OH6/KS SEX; WLI OrffS:
MGE 9 FffliSi ALL
ID, NOi 342! 3422 3423 3«4 3«S 3126 342? 3«8 3«? 343J
PROSTATE NNNNNH HHN
LYMPHOCYTIC INFlLTiftli (2> - - -
OWRIES
LTERU3
EYSS NNNNNNNHNN
(Hipcrt Cuntinuid)
ni-9
248
-------
PATHOLOOY ASSOCIATES, INC,
STUDY KO. 5223.07
SUBOTCN1C TffldClTY OF HETA-CRESQL
IN SPBiGiJI-aWLEY IAT5
Tabulated Animal Data
PROJECT ID: HCRE50L 6IOOP: WS/K5 SEX: mi£ MYS: ALL
PAGE 10 FATES: ALL
19, Nfl: 3421 3«2 3423 3«4 3425 3«4 3427 3428 342? 3438
7HS8 TISSUES AND LE5IWS:
(End irf leport)
249
III-10
-------
PATHOLOGY ASSOCIATES, INC,
STUDY HO. 5221,07
SUBOTIWJC TQXICITY OF HETfl-CRESOL
IN SPRflSUE-MUlEY RATS
Tabulated Animal Data
PROJECT IDs MCHE5DL EROUP; SHI/KB SEX: FEWLE MYS; AU
MCE i WFE5: ALL
flUHU ID. NO: 3541 35« 35-13 35
P«CREAS • H NNNNNNNN
ACIWR CaL AIRWHt - C2)
PITUITARY NNNNNNNNNN
Continued)
9 P 0
^v^ ".^ \f
III-ll
-------
PATHOLOGY ASSOCIATES, INC.
STUDY HO. 5221.07
SU8CHRON1C TttdCITf OF HETA-CRESQL
IN SPlW6yE-MUlEY RATS
Tabu!ated An imal Data
ID: HCRESQL 6ROUP: OHS/K3 SEX; FBttU DAYS: ALL
PAGE 2 ' FATES; ALL
mm. 10. NO: 3541 3542 3S43 3544 3545 354<5 3547 3548 354? 355D
WfRQIO N H N H N N
MRYflNAL OUCT CYST - <2> - - !23 (1! - <2>
MWTHTR01D NUHNNHUNUN
TMCHW ; NHKNNNNHNN
Eso?meus NNNNNNNHHN
ADREHfiL BLAND NNNNHHNNNH
IINS
LWHOCYTIC INFILTIWTS.PERW <2> <2) <2> <1) <2> (2) <3)
INTERSTITIAL INFlAfWlTIW <1> ----(!>--• (D
HEART NHNNHNNHNH
AIRTA NNNNHKKNNN
CflLCN NNHNNHNHNN
DUODfflifl NHNNNNNNNN
FDRESTtHACH NNHNNHNNHN
-------
PATHQLOOY ASSOCIATES, INC,
CTUDYNO, 5221,07
SUBCHION1C TQK1CITY OF META-CSE30L
IN SPBWUE-OAULPf f&TS
Tabulated Animal Data
PROJECT ID: NCRSSOL GOTi DHfi/KS SEX: FEWLE OftYSi All
M6E 3 WTISi ALL
ID, NOs 3541 3S« 35« 35« 3545 35« 354? 3541 354? 3550
STCWCH NNHMNNKNNN
SKIN NNNNNNNNHN
SU«0 HHNNHNNHNH
KUSCLI NNNHHNHHNN
LIVES N N N N N H
JNFWtWIEN --- -
LYKPKOCYTJC INFILTRATE «)
TESTES
PROSTATE
NNNNNNNHNN
KIWEY i NNNNNNNN N
HEPH80MTHY <2> -
HfOSMPHROSIS, EHIWTSRftL 3-
URINAL BUBOES NNNNNNNNNN
(Repcrt
'? K 9
A. O 4
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 522J.07
SUBCHRCN1C TWICnY OF HCTA-CRESCL
IN SPWGUE-MHLEY RATS
Tabulated Animal Data
PROJECT 10; NCRESOL SRQiJP: OHB/KB SEX: FEMALE CAYS! ALL
MSE 4 • MIES: ALL
mm. ID, NO:
WAWES
3541 3542 3343 3544 3545 35« 334? 3548 3549 3550
NNNNNNNHNH
UTERyS
NNNNNNNNNH
GWJX
NNHNNNHHNN
EYES
NNHNNMNNNN
(Report &3(itJB«fd)
TTT.Id
-------
PATHOLOGY ASSOCIATES, INC.
OTWNO. 5221.07
SUBCHRONIC TOXiCm QF HETA-CHESQl
IN SPMGUE-OfiUlEY MS
Tabulated Animal Data
PROJECT ID; HCRESfll CROUP! OH6/KS SKs FE»L£ DAYS: ALL
PASS 5 WTB: All
ID. NOi 354} 3542 3543 3514 3545 354
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221,07
SIOTKWIC TKICm OF HFWKRESQl
IN SP1W61I-MULEY RATS
Tabulated Animal Data
"PROJECT IDs MCSESOL SROUP: US/KB SEX; FEWU.E DfiYSj AIL
PAGE & FATES: ALL
(Him. IB. NO; 3551 3552 3553 35S4 3555 3SS4 3557 3558 355? Kid
BRftlN NNNHNHHNNN
SCIATIC NEWE ' MNNNHNNNHK
SPINAL CORD NNNNNHHHNM
BGNI NNNNNNNNNN
80f€ f«RROU NNNNNNNHNN
SlWffl NNNHNNHNNN
LWPH NODE N N H N N N
OTEIPWSIA, LWPHOI3 ' 2 - - 2 i
WYKUS N N N N N
W81QRRMG! <2) (1) <2>
NHNHNNNNHN
NMKNNNKNNN
THYROID H H H N N H
ffilRYQNAL OUCT CYffT (2) - <3> (2) <2>
(Report Contiruid)
111-16
-------
PATHOLOOY ASSOCIATES, INC.
STUDY NO, 5221,07
SU8CHSON1C TDXIC1TY OF HCTA-CRESOL
IN SPIM5UE-OAULIY RATS
Tabulated Animal Data
ffOJECT 10; NCSESOl SROUPs W8/KS SEX: FEWLE MYS; ALL
PflSE 7 FATES: ALL
FftRflTHtROlB
ID, NOi
3351 3532 3533 3554 3555 3554 3557 3533 3S5? 35
HUUUKUNHMH
TRACHEA
HNNNNNNHNN
NNNHNNN
NN
NNNHNNNNNN
IUNS
LWHOPfTIC INF1L1RATE.PESW
INTERSTITIAL INFLWtMTlQN
i€M!«RHA6E
<2) <2>
<2)
<2>
(2)
(2)
HEART
NNNNHNHNMH
AORTA
NHNK'HHKNHN
COLON
PftMSlTE
NNNNNNNHN
DUOOENU1
NHNNHNHNHN
FORESTCMCH
NNNNNHNNNN
(Rtpoct Continued)
> o
111-17
-------
PATHOLOGY ASSOCIATES, INC,
NO. 5221.07
SU8CHRONIC TOX1CITY OF HEW-CSSSQL
!N SPiWGIJE-WJLEY WTS
Tabulated Animal Data
PROJECT IB; NC8ESOL GROUP: »S/K3 SEX: F9*lLE OAYS: ALL
MGf 8 FATES: ALL
IS, NO; 3551 3552 3553 355
SPLEEN NNNNNNMHNN
KICNEY HNN NHHHN
LWPHOCTTIC INFILTiWTE - - - -<2>- - - - . -
OTRIWiPHtOSJS, 1WIWTEM 2 - - - 2
WlWXt 8WODER NNNNNI4HNNN
1E5TES * i i * * * * * » »
PROSTATE * * » * * * • * * *
BMRIES NNNNNHNNNN
JRjpcrt Continued!
« r. 7
f» tj 5
111-18
-------
PATHOLOOY ASSOCIATES, INC,
SltlDYNO, 5221.37
suewcNic Toxicm OF HETA-CRESCI
IN spwouE-mEr RATS
Tabulated Animal Data
PROJECT IDs HdlSOL GROUP! OHG/KS SEX: FBttLE MYSs All
»6! 9 MIESs ALL
IB. NO: 3551 3552 3553 3554 S555 3554 3557 3558 3559 35
tITESUS NNN NHHNN
: 2 2
CEWIX NNHNNHNNNN
EYES NNNNNNNNHN
111-19
-------
PATHOLOGY ASSOCIATES, INC.
STUDY.NO. S22S.07
SUBOiRIMC TKJCm OF META-CRESOL
IN SPM6UE-MUIET WTS
Tabulated Animal Data
PROJECT ID; NCHISOL GROUP; MS/KG SEX: F9WLE MYS; All
Pftffi 11 : FATES: ALL
ID, KOi 3551 3552 3553 3554 3555 3554 3557 3558 3559
MR TISSUE!
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221,07
SUICHRW1C TOXIC1TY OF META-CRE5QL
IN SPMKIE-WM.EY RATS
Tabulated Animal Data
PROJECT ID: HCSESOL BROUP; 5OTS/XS SiX: WU WYS; fill
WOE 1 WTES: fill
!0, NO; 3443 3444 3445 344? 345H 3454 3455 345i 3457
mw » » « * • « i • i i
SCIATIC NEWS * » * * * » » * *
SPIW4L CflRO itiiiiiif
BONE ii*i*itti
8£NE (WRBW i i I i i i i * i
aLIVARt 6UW5 i i i i i i > t i
HOTIBUWR LWH NODE f » « * * * « J i
THWUS *i«i**ii*
PWCREAS i i i i i i i i i
PITUITARY , ' * * * * * * » i *
IffifSWB ' * f i i « i i i i
(Report Caitiitunl)
TTT-71
-------
PATHOLOGY ASSOCIATES, INC,
STUDY NO, 5221,U7
SUIOTONIC TOXICITY OF MEW-CRESQL
IN SFWSUE-WHLEY RATS
Tabulated Animal Data
PROJECT JD: MCRESOL BROUPs 50KI/K6 SEX; HftLE MYS: ALL
WSE 2 FftTES: ALL
ID. KB! 3443 34« 3445 3449 3453 3454 3455 345i 3457
§ i * § » i § § »
E50PW613S itfitiiti
»RWl 8WKD * t t i i i t i i
LL'iS »i»ilti»»
KEAirr i i i i i i s i i
ADRTfl ' *lli****l
COLCH i»ii**iji
DUODENlfl »ti>*iiit
FORESTOWCH . I * * t i t i t i
6UWOUWR STCHACH * * i t i i i * «
SKIN i*ii»iii«
(Hsport CcntinusdJ
2C1
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO. 5221.07
SUBCHRNIC T OKI CITY OF META-CRESOL
IN SPMGUE-MUIEY RATS
Tabulated Animal Data
PROJECT ID! MC8ESOL EROUP: 5GHG/XG SEX: WLE DAYS: ALL
PAGE 3 FATES: ALL
WML ID. HO! 3443 3444 3445 3449 3433 3454 3435 3454 3457
SKELETAL MUSCLE * * « * * * * * *
LIVER IN N
LWHOCYTIC INFILTRATE <2>
CYTDPLASMIC WOJCLATICN <2) - - - <1>
NECROSIS <2>
SPIEEN
X1CNEY » 1 i 1 i * »
NEPHRQPATHY - 2 - - - - - 1 -
URINART BLADDES l » 1 « i i I « I
TESTES iitttiiii
PROSTATE I 1 J » i * 1 J »
OUARIES »»»»*§**»
UTERUS * * * * * » t t *
CEWIX i » i **»»»#
(Report Continued)
TTT
-------
PATHOLOGY ASSOCIATES, INC.
STUDY ND. 5221.07
SU1CHRCNIC TQXICm OF HETA-CRESX
IN SPIWGUE-MyiEf MS
Tabulated Animal Data
RWECT 10: NCSESOl ttWft 50H6/KS SEX: ffcLE WYS: fill
MBE 4 WTES: All
ID. NO: 3443 3«4 3445 3«? 3450 3454 3455 3454 3457
£Y£S * i • N i i i • i *
(Atport Coniinufii)
111-24
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 3221.07
SSCHRCNIC TOXICm CF HEM-CRESfll
IN SPHflGUE-WWLEf SATS
Tabulated Animal Data
WOJKT 3D: HCRESO!. SSOiP; 5WS/K6 SEX; NftLE MYS: ALL
MGE 5 FftlHS: M.L
IS, NOi 3«3 3«4 34« 344? 3450 3454 3455 345i 345?
THEB TISSUES flND LESICNSi
(End af R»port!
264
111-25
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. S22I.07
SBBCHRtNIC TKlCJTf OF HTO-C3ESOL
IN SPWBUE-MULFf MTS
Tabulated Animal Data
PROJECT 10: HCRISUL GROUP: SONG/KG SEX: FBttlE MtS: ALL
M6£ 1 • FtffES; ALL
ID. HO: 357! 3573
IRAIN i »
ESATIC mm i *
SPIWL CCID * »
BONE i »
ION£ mRROU t »
GUW ' » *
LWH NODE * »
TKfflUS . • *
PfWCSEAS * »
pnurwsr • * *
IHYHOIB * *
* »
Coniinutd!
TTI-26
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO, 5221.07
SUBCHRCN1C TOK1CITY OF META-CSESQL
IN SPMGUE-OftaLEY MTS
Tabulated Animal Data
PROJECT 10: MCSESCL 68QUP: 50MS/K6 SEX: FEWLE DAYS; ALL
PftGE 2 WTESs ALL
TRACHEA
3D. HO:
3571 3573
I »
ESOPHAGUS
ADRENAL GLAND
lUNS
HEAST
AORTA
EDLIK
DUOOENIM
FORESTCNACH
STCWCH
* *
« *
SKIN
WftttRY GLAND
« *
(Report Cantinued)
266
iir-27
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO. 5221.07
HI8CHRCNIC TCKIC1TY OF HETA-CRESCL
IN SPRAGUE-OfiULEY SATS
Tabulated Animal Data
PROJECT ID: KCRESOL GROUP: 50MG/K5 SEX: FBttLE DAYS: ALL
PftGE 3 FATES: ALL
ID. NO! 3571 3373
SKELETAL MUSCLE * *
LIVES « i
SPLEEN * »
KIDNEY i i
URINARY BLADDER * »
TESTES i «
PROSTATE » »
OVARIES t H
UTERUS * I
CWIX » i
EYES * i
(Report Continued)
o /? -•
^ b *•
111-28
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221.0?
SUBCHRONJC TIKI CITY OF HETA-CSESffl.
IN SPJM6UE-MWLEY RATS
Tabulated Animal Data
PROJICT IB: KCRESOL 6IOUP: 50H5/K6 SEX:
M6E 4 FATISsALL
DAYS:
ID, Ni:
OTHER TISSUES *D LESIENS:
LN-HEMORRW6E
3571 3571
(End of flipgrt)
68
T1T-9Q
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.87
TDXICITY OF HETA-CRESOL
IN SPW6UE-MULSY RATS
Tabulated Animal Data
PROJECT ID: HCIESQL SiQtJP: 150HB/KI SEX: WIE • MYS: AIL
PAGE 1 FATES; ALL
imi ID. NO! 3471 3«9 3484 3485
mm t t i *
SCIATIC NEWE * « » 1
SPINAL CORD till
BONE i i i i
3CKE KARROU i i 1 i
SALIVAITf SUWD . » » i i
JWflJIBUWR LYMPH NODE * * » *
THWUS i « * *
' i i » i
* f § *
TKTR01D
MSWWRDIO ' » f » *
(Report Continued) 'i 6 9
111-30
-------
ESQFtttGUS
LLN6
COLIN
FOBESTEK4CH
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5225.0?
SWCHiGNie TKICITY OF NETA-CSESOl
IN SPIfcGUE-OftULE* RWS
Tabulated Animal Data
PROJECT 3D: MCRESDL BMUPj I!OM6/Kfi SEXs KW.E DAYS; ALL
WSE 2 WTE5,' *U
TOCHK
ID. NO:
3478 347? 3484 3418
* * » §
* i I
DCCOfflUH
f i i
SUWULAR STCWCH
i * »
SX1K
* * *
(Report Continutd)
270
-------
PATHOLO8Y ASSOCIATES, INC.
STUDY NO, 5221.0?
SUBCHRON1C TOXICITY OF HETA-ERESOl
IN SPRA6UE-MULEY RftTS
Tabulated Animal Data
PROJECT 10: MCRISOL SROUP: ISMS/KB SOU HALE DAYS:
PAGE 3 FATES; ALL
IB. ND: 3478 3479 3484 3451
SKELETAL HUSCLE * » i i
LIVER » H
CHOPLASUC WCW3LATIDN - <2) <2)
SPLHHN
KIDNEY
mimm BUBOES
ATROPHY,SB1!NiraOyS TUIULIS <3)
PROLATE
OVARIES i t » i
WEUS i i
CERVIX i * i »
EVES i i * i
(Rtport Continysd)
271
111-32
-------
PATHOLOGY ASSOCIATES, INC,
STUDY NO. 5221.07
SUBCHISWIC 70X1C1TY OF KE!A-«ES£JL
IN SPIMUE-MULt? RATS
Tabulated Animal Data
PROJECT JOi MCSESOL SSOypi iSOME/KB SEX; MALE WYSi ALL
W6I 4 FATES; ALL
(WlfWL ID, NOi 3478 3479 MM 3488
me TisstiES
(End 9f Report)
61 i*i f)
111-33
-------
PATHOLOGY ASSOCIATES, INC
STOYN8, 5221,0"?
SJBCHMK1C TOXICITY Of NFFA-CRESQL
IN SPRflfiUE-MWlEY »TS
Tabulated Animal Data
PSOJECT 10: HCHESDL GROUP; 150MG/KS SEX; FfflALi WYSs ALL
Ml I FATES; ALL
10. NO: 3<02 3m
8WIIN * »
XlftTIC NEHWE * i
mmi COSB » i
idi * *
EtME mSROU i *
»LIMW fiUWD i 1
NWBIiUWR LWPH HQDE ' * i
TKfflUS i J
f »
PITUITARY
THYROIO
MWTHYR010 i I
(Report Continued) 2 7 3
111-34
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHKN1C TOXICITY OF META-CRESOl
IN SPRAGUE-OAULEY WTS
Tabulated Animal Data
PROJECT ID: HCRE5CL GROUP: 15WQ/KG SEX: FEttLE MYS: AU.
PAGE 2 FATES: ALL
AN1NU ID, NO: 340? 3404
TfWCHEA » i
ESCPWGUS i i
ADREhKL GLAND * !
LUNS i »
HEART * »
AORTA i I
CGLCN * »
DUCOENlfl * J
FORESTCreCH
JTOWCH
SX1N
BLAND
(Rtport Continued)
111-35
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 3221.07
SUBCHMN1C TCKIC1TY OF META-CSESOL
!H SPfMBUE-MULEY RATS
Tabulated Animal Data
PROJECT IDs NtSISei GROUP; ISUHS/KS SEX: FBtfLE MYS; ALL
flftSE 3 ' FftTESs ALL
ID, NO:
SKELETAL HUSCLE
3402 3404
t !
LMR
HEPATOOIAPHRAWTIE NOOUIE
SPLEEN
K1WEY
t i
BLADDER
* i
TESTK
PROSTATE
CWWUES
WEIUS
CEFW1X
i i
EYES
i i
(Report Continued!
275
III-36
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221,07
SUiCHMNie TOX1C1TT OF HEW-CRESQl
IN STOGUE-MH.SY »TS
Tabulated Animal Data
PRDJICT ID; MCREiOL IROUP; I50HE/KS SEX; FB1ALE DAYS: All
PftGi 4 (WES: ALL
IB, NO: 3402 34J4
m TISSUES m imm>,
JEJIWUH-HOSHAL - P
(End of RipertS
t~S m
,'.• /
111-37
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.Q7
SUBCHRCNi: TOX1CITY DF KETA-CRESCL
IN SPRAGUE-W1ULEY RATS
Tabulated Animal Data
PROJECT ID: KCRESOL GROUP: 45GH6/KG SEX: MALE DAYS; ALL
PAGE ! FATES! ALL
10. NQ: 3501 3502 3503 3504 3505 3504 3507 3508 3509 35!0
BRAIN NNN NNNNNNN
SCIATIC NEfWE NNHNNHHNHH
SPlWiL CORD NNHNNHNNNN
KNE NNHNMHNNHN
BUE HARROU NNNNN.NNNNN
SALIWRY SWHO NNNNHKNNNN
WWOIBUWR LYMPH NODE N N
WERPLAS1A, LWPH01D 222-2-2222
TlfrtlUS N M N K N N
HD10RRWSE - - - <2) - - - <2> <2) <2)
HNH NNNNNK
HBIQRRtWEE <2)
PITUITARY NNNNNNNHNN
(Report Continued)
277
TTT
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO-, 5211,87
TIKI cm OF META-CRESOL
IN SPSMUI-WJIEY MS
Tabulated Animal Data
PROJECT IDs HCRESOL BROUPs 4MHOT6 SEXs MM.E MYSi ALL
FADE 2 FATES: ALL
IB. HO: 3501 3502 3503 3504 35(13 3!8^ 350? 350S 3SO? 3518
TOO!!) ' N " N N (I N
EHBIfCWL WJCT CYST <2> •- . - - (2) (2) <2>
ATSOPW - [31
WRflTHYSOID HNNHUNNNMN
TRACHEA HNNNHHHKMH
ESOPfttSOS NNNNNNNNNN
NNNHMHNNHN
LIW5 N H N N N N
CENBESTION - - - !31 - - - - -
LYHPHCCfTIC INFILTRATEjPESW ' <2) - - <3>
IKTE1JTIT1AL INFlAtHTltM <2)
HEART N H H N N
WFW1, ,CHRCNIC, WQMRDIIH (1) (2) (3> <2) (3)
NNHHHHNNNN
CCLCN NHHNHMNNN
DUEDENU1 HNNAHNNNHN
(Rejort Can!inu*d)
111-39
-------
PATHOLOOY ASSOCIATES, INC
STUDY HO. 5221.0?
TIKI CITY OF META-CRESOL
IN SPW60E-9fl4LEr WTS
Tabulated Animal Data
WOJECT IDs MCRISDL fiROlff: 45CHG/KS SEX: HftLE UftlfS: ALL
MSI 3 . FATES i ALL
ID. NO: 35fll 3502 3503 3504 3505 3504 3507 3503 3S« 3510
FflRESIWttH NHNHNNNHNN
Gl^OUWR STTOCH ' NNNNNHNNNH
SX1N NHNNNNNNNH
IWtWKY SMHO - NPIINNUNNHU
SKELETAL HUSaE ' HNNKNMNNNM
LIVER N N N;N H N N H H
NDDULE P
.NNNNNHNNHN
K1WEY N H N M H N
LWHOCYT1C INFILTOTE <1> !2) -
mmmrim, RBWL TUBULES - - - <2> - <2)
UR1WRY BLAODES NNNNNNNNHN
TESTES HNHNHNNN N
ATROPHY.SEMINIFEROUS TUSUIES <2>
(Report Contiiioid)
279
ITT -/in
-------
PATHOLOGY ASSOCIATES, INC.
STtlBYNQ. 5221.07
Toxicm OF MEIA-CREBOL
IN SPRftGUE-OAUlEY MS
Tabulated Animal Data
PtOJICI ID: NCBESOl SROUP? 450H6/KI SEX: *LE DATS: AIL
4 WfES: ALL
ID. Nfl: 3501 35J2 3S83 3584 3505 3504 350? 3SD8 350? 3510
P80STATE KNNN NHNNK
LWPHOOT1C INFILTRATE (2)
UTERUS iliiltil*!
i § i
PfES HNNNNNNNNH
Continufd)
111-41
280
-------
PATHOLOGY ASSOCIATES, INC,
STUDY NO. 5221.07
StliCHRfWlC TOX1CITY OF HEIfl-CSESOL
IN SPftW-MULEY JtoTS
Tabulated Animal Data
TO.JECT IB! KC8ESQI BROUP: «OHE/K5 SiX: WLE OftYS: ALL
PflSE 5 FATES: ALL
(Wfttt IB. NO; 3501 35U2 3503 3504 3585 3504 3507 3553 350? 3S1I
TAB TISSUES tfiD LESICNS:
(Report Ctsntinurrf)
SSI
111-42
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221,07
SUBCHRtniC TOXIC171 OF META-CRESOl
IN SPRA6UE-MULEY SATS
Tabulated Animal Data
PROJECT ID! MCS150L fiROUPs 451K6/KS SEX: WL1 DAYSi All
PftfiE 4 FATES: ftll
ID. NO: 351! 3SI2 3513 3514 3515 3514 3S1? 3518 351? 3328
HNHHHNNN N
HBiORRWGE (D-
KWTlt NERVE NHNNHHHNNN
SPINAL COfiB NHNNNNNNHN
i£KE HNNHKHHNHN
BDNEMflSRIW ; NNNNNNNNNN
»LJVAiY 6WNB NNNMNHHNHN
LWH NODI
, LYMPHOIQ 2213222222
IHfflUS NNNHHHNHN
WNCRftS NHNNMMNNNN
P17UITAIW H N N N N N N U
CYCT, PARS MESHEB1A (2) - - -
(Riporl Continued)
*? 8 9
'
TTT-4T
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 521! J7
SUSCHRDNIC TflXIClTY OF META-CRiSOL
IN SPRAGUE-WULEY RATS
Tabulated Animal Data
PROJECT ID: HCREiGL BROUP; 450KG/KS SK: WLE DAYS: ALL
PftfiE 7 FATES; ALL
ID, NOs 3511 3512 35J3 3514 3515 35U 351? 3518 351? 3520
TOR01D NNH NNNNN
WCT asi (2) <2>
mRATHTROID . NHNNNUNUNU
TSACHM HHNNHNNHNN
ESOPiWGllS NNNNNNN-NNH
BUND NNNNNNNNNN
L!KB N H
LWHOCYTIC INFILTRflll.PESW <2> - <1> <2> <2> - <2> (2) <2) <2)
INFWffttTUSH - - <2> <2> - - <2)
HEftfTT . NN NNHNNH
ttfflAH.jCHRfNIC, HYOCARDIIW - - (2) <2> ' -
NNKHNNNNNN
COL!K NNNNNHHNNN
DUQB0M! N'HNNNHN'NHN
8i> n
^ (5
111-44
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221,07
7K1CITY OF HE7A-CRESOL
IH SPf»SUi-«M.EY RATS
Tabulated Animal Data
PSUICT 10s MCRESQL BRBUP: 45»fi/KB SEX: MALE MYS; ALL
MM 8 FATES; ALL
ID, NO: 3511 3512 3513 35 U 35S5 351 i 351? 3S18 3519 3528
FBREOTOT NNNNNNHUHN
STOhACH ;'NNNNNNNNNN
SKIN NNNNNNNNNN
IWIWRf 6LW UUyNNNNNNU
SKELETAL H'JSCLI NNHHNNN'HNH
LIVER NNNHNHNHNN
N"N HN H H N N N N
KIDNEY KNH NNHNN
NEPHSOMTHY - - (2) .-.,..
RE6ENESATI1W, RB«L TUiUUS - - - - <2>
BWDBES NNMNHNNNNN
TESTES HHNNHNKNNH
PROSTATE HHN NNHN H
LWHOCfTIC 1NF1LT5ATE <2> - - - - <2>
Coniinuid)
III-45
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221.07
SU8CTONIC TOO CITY OF META-CSESflL
IH SPJMiUE-D«LEY RATS
Tabulated Animal Data
PiOJECT II: HCRESOL SROUP; 4SOH(yXG SEXs MALE BAYS! ALL
WEI f FATES: ALL
ID, NO: 3511 3512 3513 35S4 35SS 35ii 351? 3518 351? 3520
OWJ1ES i i * i * * i i » »
EVES . HKNNNNHKNH
(Report Cantinuid)
111-46
^ c ^
ri O
-------
PATHOLOGY ASSOCIATES, INC,
STUDY NO. 5221,07
KJBCH1DN1C 1CKIC1TY OF HETMRESOl
IN SPMBUE-MLFf WTS
Tabulated Animal Data
PROJECT ID; HCaESfll 6ROUP: «OMS/KG SEX: WL£ MYSj ALL
WSE IB FATES s ALL
mt ID. NO! 3531 3512 3513 3314 3515 3514 351? 3518 351? 3520
ITHEi TISSUES (WO LESIUIS;
(Entf of Report)
286
111-47
-------
PATHOLOGY ASSOCIATES, INC,
STUDY Nfl, 5225.07
Toxicm OF NETA-CRESOI
IN 5PW6UE-MUIEY RATS
Tabulated Animal Data
PROJECT ID:
»G£ 1
iROU?: 45CMSXKG SEX: FSttLE DAYS: ALL
FATES: ALL
10, NO;
BRAIN
3431 3&22 3^33 3«34 3£35 3^36 3^37 Um 3
-------
PATHOLOQY ASSOCIATES, INC
STUDY NO. 5221,07
SUiCHRONIC TOXICm OF NEW-CRESOL
IN SPSSGUE-MULK RATS
Tabulated Animal Data
WQJECT ID; HCRESOL EROUP: 45BN6/KS SEX: FEMALE DAYS! ALL
PAGE 2 FATES: ALL
i ID. NO; 3m 3432 3<533 3134 3£3S UU W7 3iS33 343?
KYKJ1D , H N H N N
B1IRYOWL OUCT CYST <2) - <2) - - <2) - (2) <2)
NNUNNUN'JNN
TRACHEA NNNNNNHHNH
ESOPttSOS NNNNNNNNNH
5UWD HNNNNNNHN-H
LUNS , N N N
IfflPHUCmC INFILTWTE.PESIV - - <2) <2) <2> - (2) - (2) <»
IMTERSTIIIAL INFLfWttTlDN <2> -
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221,07
SUBCHRONIC TOXICm DF HBA-CRESOl
IN SPMUE-WiLEY OTS
Tabulated Animal Data
PROJECT ID; NCRESfll GROUP: 45HHG/TO SEX: FEWlLE MYSs AH
WS J FATES.' ALL
ID. NOs . 3m 3432 3633 3«4 3435 3«4 3
BUBOER ; HNNNNNNNNN
TESTES iiiiiiiiti
PROSTATE *****ii}«»
(Rtpoi-t Continutd!
111-50
-------
PATHOLOBY ASSOCIATES, INC.
STOYNB, 5221.11?
SUSCHRONIC TOXICJTY OF META-CRESOL
IN SPSftGUg-WULEY RftTS
Tabulated Animal Data
PROJECT JD: MCRESOL 8ROUP: 450NS/KB SEX; F&WLI MYS; ALL
WBE 4 FATES: All
ID. NQs
WAEIES
3631 3«2 3433 3«4 3<§35 3434 3437 mS 3H? 3M9
NNNNNHNNNN
SJTERb'S
DILATATION
MNNNMNHNH
CEfWIX
NHNNNNNNN
NHNHNHNMKN
(Ripoft Continud)
111-51
290
-------
PATHOLOGY ASSOCIATES, INC.
NO. 5221 ,07
gjBCHSflNIC 7CKIC1TY OF NETfr-CRESOL
IN SPWGyE-MILEf RATS
Tabulated Animal Data
PROJECT ID; NCiESQl SSOtJP: «OMG/KB SE<: FSfcLE OftKSs flU
M6S 5 ftilKi «LL
IB, NO; 3«i 3432 3«3 3634 3«5 3434 3437 3*538 3^3?
TISSUES m imm-.
(Rtport Continued!
9 Q
/-, «j
ITI-52
-------
PATHOLOGY ASSOCIATES, INC.
STUSYNQ. 5225.0?
SUBCHtWIC TOO Cm OF MEIA-CRESd
IH SPWeiJE-DSJlEY ftffS
Tabulated Animal Data
PROJECT ID! HCRESOL SROUPt 45W1G/XS SEX: FBtfLE DAYS: ALL
PAGE 4 FATES: ALL
ID. NO: 3«1 3W2 3M3 3d« 3i45 3444 3647 -3W8 3«9 3«
8SMIN NMNNNHNN-NN
SCIATIC NEWE NNNNHNHNNM
SP1WL tSRD NNHNHHNNNN
ICNE H-NNNNNNNNM
SIM mRRCU . NKNNHNNNNN
»LIVfifiY 5UWD NNNHNNNHNN
LWPHHOOE H
HYPEJPWSW, LWHOID 122-222222
' NNNHNNNHNN
P«
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO. 5221.37
SUSCHMNICTDXICITY OF HETA-CffiSCL
IN SPRMUS-MUIEY »T5
Tabulated Animal Data
PROJECT ID: HCRESOL 61WP: 450H6/K6 SEX; FfflftLE MYS; AH
MSE 7 FATES! ALL
MfiATHYROlD
ID. HO:
3445 U42 3143 3^4 3^45 ' UU 3«7 3448 t
HNHUUONNH
3430
HNNHNNNNNN
ISOPWOUS
H NHNNHHNNH.
6U«D
NNHMHHNNHN
LWS
WPHOCYTIC 1HFILTSATE,P£S1U
<2)
N N N
<2> - <2) <2> - <2> (2>
NNNNHNNHHN
MiTTA
NHNHNNNNNH
MLCN
NHHHKHHNNN
DUOCENIK
NNNNNNHMNH
FQRESTQfttCH
HHNHNNHNNH
6UNW1LAR
NHNHKNHNNN
Continaed)
rp
111-54
-------
PATHOLOGY ASSOCIATES, INC,
STUDY NO, 5221.37
SU8CHICNIC TflXICm OF META-ERE50L
IN SPRftfflJE-Ort&Ef MIS
Tabulated Animal Data
WWECT IB-, NCRESOL GROUP: 458MG/KB SEXs FEmLE DAYS: ALL
MGE 8 ' FftTSS: fill
IB. NOi 34« 3«2 3ii43 3444 3i45 3i« 3M7 3i4i 3M? 3158
SKIN NNNHNNNNHN
Wif«iY 6LWO ' KNNHNHNNNH
SCRE7AL HUSttE • NNNNNNNKNH
LIVES • NMNNNNNNN
FATTY £I*N6£ - - -CJ>
SFLEW ' NNNNNNNNNM
KIDNEY NHK NNHNNN
, SBW. TUBULES ---
iUDDES ' -HNNNNNNHNN
TISTES » » * » * * * * * *
PROSTATE I * * i * * « » * *
OMAR1ES NNNNNNNNNN
UTERUS NMMNNHNKNH
(Ripert
61 Q ft
s. M '•»
111-55
-------
PATHOLOGY ASSOCIATES, INC
OTDY NO, 5221.07
SJBCHRCNie ItKlClTf OF METft-CSBOL
IN SPRABH-MULEY fiffTS
Tabulated Animal Data
PROJECT ID: MC8ESDL GROUP! 45GHG/KS SEX: FBtttE DAYS: AIL
Mffi f . FATES: flLL
fllllttL U. NO;
3441 3^42 3W3 3MA Ml 3m ~U47 3i48 3449 3
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.117
SJBCHRCNIC TGKICm OF ME7A-CRESQL
IN SPMGUE-WJLEY RATS
Tabulated Animal Data
PROJECT ID: KCRESQL GROUP: 450HG/KG SEX: FBttLE WYS: All
PAGt 10 FATES; ALL
ID. HD: 3^1 3^2 3^3 3^4 3445 3444 3447 3448 344? 3450
me TISSUES WD LESIBS;
WGINA-CTST ...... <2)
(End
b>
TTT.i;7
-------
IV 6ROSS VS. MICROSCOPIC FINDINGS
-------
PATHOLOGY ASSOCIATES, INC.
• STUDY NO. 5221.07
SU8CHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAUiLEY RATS
Correlation o-f Gross Sc Micro Finding*
'ROJECT ID: MCRESOL GROUP: OHG/KG SEX; MALE DAYS; ALL
'AGE 1 FATES: ALL
ANIMAL NO: 3411 PATHOLOGY ID. NO: 853411 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH:• DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>LIUER-SLIGHTLY PALE AMD SWOLLEN LIVER- CYTOPLASM!C VACUOLATION
ANIMAL NO: 3412 PATHOLOGY ID. NO: 953412 PATHOLOGIST; LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PP~f3ABLE CAUSE OF DEATH: DAYS ON TEST i 90
TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3413 PATHOLOGY ID. NO: 853413 PATHOLOGIST; LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH:, DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY!
>NGL
ANIMAL NO: 3414 PATHOLOGY ID, NO; 853414 PATHOLOGIST; LHB
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
IV-1
f"nn fr j
-------
f'f, t 1"H_»U uo i (- .'oouc- i i-J I i_ 'o , .•,!•,•_.
STUDY NO. 5221.07
SUBCHRONIC TOXICITY OF META-CRESQL
IN SPRAGUE-DAULEY RATS
Corre 1 a.-* i on o-f Gross & Micro Findings
=ROJECT ID: MCRESOL GROUP: OMG/KG SEX: MALE DAYS: ALL
=AGE 2 FATES: ALL
ANIMAL NO: 3415 PATHOLOGY ID. NO: 853415 PATHOLOGIST: LHB
ANIMAL FATE! SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY:
>LIUER-SLIGHTLY PALE NO COROLLARY CHANGE DETECTED
ANIMAL NO: 3414 PATHOLOGY ID. NO: 853416 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>•':••'•'•'EY-1 (5X5MM) CYST IN CORTEX OF NO CYST WAS NOTED IN THE KIDNEY
R. T KIDNEY • CORTEX
>LIUER-SLIGHTLY SWOLLEN NO COROLLARY CHANSE DETECTED
ANIMAL NO: 3417 PATHOLOGY ID. NO: 853417 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
299
IV-2
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PATHUU, ULj'T
STUDY NO. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
ROJECT ID; MCRESOL GROUP; OMG/KG SEX: MALE DAYS: ALL
AGE 3 . FATES: ALL
NlMAL NO: 3418 PATHOLOGY ID. NO: 853418 PATHOLOGIST; LHB
NlMAL FATE: SCHEDULED SACRIFICE
ROBABLE CAUSE OF DEATH: • DAYS ON TEST: 90
EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
H1STO-SLIGHT ROUND 3 X 3MM DARK NO COROLLARY CHANGE DETECTED. THE
DISCOLORATION IN CORTEX OF RT. CAUSE OF THE KIDNEY DISCOLORATION
KIDNEY , NOTED GROSSLY WAS NOT DETERMINED.
NlMAL NO: 3419 PATHOLOGY ID. NO: 853419 PATHOLOGIST; LHB
.NIMAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
:l;.? ^ENCE TO NECROPSY RECORD: RELATED HI STOPATHOLOGY:
•NGL
,NIMAL NO: 3420 PATHOLOGY ID. NO: 853420 PATHOLOGIST: LHB
,NIMAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3421 PATHOLOGY ID. NO: 853421 PATHOLOGIST; LH8
ANIMAL FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
IV-3
(Report Continued)
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P/rt'KOLOGY .ASS0C1 ATES , INC.
STUDY MO. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAUJLEY RATS
Correlation of Gross & Micro Findings
ROJECT ID: MCRESOL GROUP: QMG/KG SEX: MALE DAYS: ALL
AGE 4 FATES: ALL
NIMAL NO: 3422 PATHOLOGY ID. NO: 853422 PATHOLOGIST: LHi
N1MAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 90
iEFERENCE TO NECROPSY RECORD! RELATED HISTOPATHOLGGYi
LIUER-PALE AND SWOLLEN L1UER- CYTOPLASM!C VACUOLAT1QN
.NIMAL NOi 3423 PATHOLOGY ID. NO: 853423 PATHOLOGIST: LHB*
.NIMAL FATE: SCHEDULED SACRIFICE
-.ROBABLE CAUSE OF DEATH t DAYS ON TEST: 90
•EFEREMCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
•K-
ANIMAL NO: 3424 PATHOLOGY ID, NO: 853424 PATHOLOGIST: LHB
iNIMAL FATE: SCHEDULED SACRIFICE
'ROBA8LE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTGPATHCLOQY:
>NGL
ANIMAL NO: 3425 PATHOL06Y ID. NOs 853425 PATHOLOGIST: LHB
ANIMAL FATE: -SCHEDULED SACRIFICE
=RQBABLE CAUSE OF DEATH: DAYS ON TEST: 50
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
*? A "I
(Report Continued) *-• V -l
IV-4
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PATHOLOGY ASSOCIATES; INC,
STUDY NO. 5221.07
SU8CHRQNIC TOXIC1TY OF META-CRESQL
IN SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
ID: MCRESOL GROUP: QMG/KG SEX: MALE DAYS: ALL
3AG£ 5 FATES: ALL
.MIMAL NO; 3424 PATHOLOGY ID. NO: 853426 PATHOLOGIST: LHB'
-»NIMAL FATEs SCHEDULED SACRIFICE
3RQSABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
ANIMAL NOs 3427 PATHOLOGY ID. NO: 853427 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NOs- 3428 PATHOLOGY ID, NOs 853428 PATHOLOGIST: LHB
ANIMAL FATEs SCHEDULED SACRIFICE ' '
=ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>HISTO-TESTES HAVE SOFT CONSISTENCY. TESTES- ATROPHY,SEMINIFEROUS TUBULES
ANIMAL NO: 3429 PATHOLOGY ID. NO: 853429 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 90
REFERENCE TO NECROPSY RECORD! RELATED HISTOPATHOLOSY:
>NGL
(Report Continued)
IV-S
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PATHOLOGY ASSOCIATES, INC,
STUDY NO, 5221 .07
SUBCHRONIC TOX1CITY OF META-CRESOL
IN SPRAGUE-OAWLEY RATS
Correlation o-f Gross & Micro Findings
ROJECT IDs HCRESOL GROUP: OMG/KG SEX: MALE DAYS: ALL
•ASE 6 FATES: ALL
,NIMAL NO: 3430 PATHOLOGY ID. NO: 853430 PATHOLOGIST.- LHB
MIHAL FATE: SCHEDULED SACRIFICE
"R08ABLE CAUSE OF DEATHt DAYS ON TEST! 90
DEFERENCE TO NECROPSY RECORDi RELATED HISTQPATHOLOGY:
•LIUER-SLISHTLY PALE AND SUOLLEN NO CAUSE OF THE PALENESS SEEN AT
NECROPSY WAS NOTED
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PATHOLOGY ASSOCIATES,, INC.
• STUDY NO, 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SFRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
'ROJECT ID: MCRESOL GROUP: OMG/KG SEX: FEMALE DAYS: ALL
'AGE 1 FATESi ALL
NIMAL NO: 3541 PATHOLOGY ID. NO: 853541 PATHOLOGIST: LHB
.NIMAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH,- DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED H!STOPATHOLDBYi
>NGL
ANIMAL NO: 3542 PATHOLOGY ID. NO: 853542 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
^ROBABLE CAUSE OF DEATH: DAYS' ON TEST: 90
?E, .ENCE TO NECROPSY RECORD: RELATED HISTOPATHOL03Y:
>NGL
ANIMAL NO: 3543 PATHOLOGY ID, NO: 853543 PATHOLOGIST: LHB
ANIHAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3544 PATHOLOGY ID. NOj 853544 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>r "
IV-7
(Report Continu&cO
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221,07
SUBCHRONIC TOXICITY OF META-CRESOL
.IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
ROJECT ID: MCRESOL GROUP: OMS/KB SEX: FEMALE DAYS: ALL
AGE 2 FATES: ALL
NIMAL NO: 3545 ' PATHOLOGY ID. NO: 853545 PATHOLOGIST: LHB
N1MAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH; DAYS ON TEST: 90
'EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
•N6L
,N!MAL NO: 3546 PATHOLOGY ID. NO: 853546 PATHOLOGIST; LHB
.NSMAL FATE: SCHEDULED SACRIFICE
5R08ABLE CAUSE OF DEATH: DAYS ON TEST: 90
?E-~RENCE TO NECROPSY RECORD: RELATED HISTOPATHOLQGYi
ANIMAL NO; 3347 •.. ••--.: 'PATHOLOGY ID. NOs 853547 PATHOLCSIST: LHB
ANIMAL FATE: SCHEDULED-SACRIFICE
=ROBABLE CAUSE OF DEATH: DAYS ON TESTs 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>MGL
ANIMAL NO: 3548 PATHOLOGY ID. NO: 853548 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221 .07
SUBCHROMIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
'RQJECT ID: MCRESOL OROUP; OHG/KG SEX: FEMALE DAYS: ALL
AGE 3 FATES: ALL
NIMAL NO: 3549 • PATHOLOGY ID. NO: 85354? PATHOLOGIST: LH6
TR!M-0!LATED PELUIS, RIGHT KIDNEY KIDNEY- HYDRONEPHROSIS, UNILATERAL
ANIMAL NO: 3552 PATHOLOGY ID. NO! S53552 PATHOLOGIST: LHB
ANIMAL FATEs SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
306
(Report Continued)
TV-<5
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SU.BCHRONIC TOXIC1TY OF META-CRESOL
IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
3ROJECT ID: MCRESOL GROUP; OMG/KG SEX: FEMALE DAYS: ALL
4 FATES: ALL
ANIMAL NO: 2533 PATHOLOGY ID. NO: S53553 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH: DAYS ON TESTs 90
REFERENCE TO NECROPSY RECORD: RELATED HI STOPATHOLOGY :
>NGL
ANIMAL NO: 3554 PATHOLOGY ID. NO: 853554 PATHOLOGIST: LHB
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
ANIMAL NO: 3555 PATHOLOGY ID. MO: 853555 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>TRIM-DILATED PELVIS, RIGHT KIDNEY KIDNEY- HYDRONEPHROSIS, UNILATERAL
ANIMAL NO; 355.6 PATHOLOGY ID, NO: 853556 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SU'BCHRONIC TOXICITY OF META-CRESCL
*IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
3ROJECT ID: MCRESOL GROUP: OHO/KG SEX: FEMALE DAYS: ALL
'AGE 5 FATES: ALL
MIMAL NO: 3557 PATHOLOGY ID. MO: 853557 PATHOLOGIST; LHB
ANIMAL FATE: SCHEDULED SACRIFICE
'ROBA8LE CAUSE OF DEATH: • DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOOY:
>NGL
ANIMAL NO: 35SS ' PATHOLOGY ID. NO: 353553 PATHOLOGIST: LHi
3N1HAL FATE: SCHEDULED SACRIFICE
=RCBA8LE CAUSE OF DEATH: • DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD! RELATED HISTQPATHOLOSY:
ANIMAL NO: 355? PATHOLOGY ID. NOs 833559 ' PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED"SA'CKI FI CE •'
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOFATHOLOSY:
>NGL
ANIMAL MO: 3560 PATHOLOGY ID. NO: 853540 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(End of Report)
IV-11
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
'RQJECT ID: MCRESOL GROUP: 50MQ/KG SB<: MALE DAYS 5 ALL'
AGE i FATES: ALL
-NIMAL NOs 3443 PATHOLOGY ID. NO: S53443 PATHOLOGIST! LHB
ANIMAL FATE: SCHEDULED SACRIFICE
3ROBABLE CAUSE OF DEATH; DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
LIUER-SLIGHTLY SWOLLEN LIUER- CYTOPLASM!C MACUOLATION
tNIMAL NO: 3444 PATHOLOGY ID. NO: 853444 PATHOLOGIST: LHB
-NIMAL FATE; SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
:£'.. £NCE TO NECROPSY' RECORD: RELATED HI STOPATHOLOGY j
-KIDNEY-1 C3X3MM) ROUND INDENTATION KIDNEY- NEPHROPATHY
IN CORTEX OF RIGHT KIDNEY.
.NIMAL NO: 3445 PATHOLOGY ID. NO: 853445 PATHOLOGIST: LHB
,NIMAL FATE: SCHEDULED SACRIFICE
'RCBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD.- RELATED HISTOPATHOLOGY:
»EYE, LEFT-CORNEA PROTRUDING NO COROLLARY CHANGE DETECTED
LIUER-PALE AND SUOLLEN NO COROLLARY CHANGE DETECTED
(Report Continued)
IV-12
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PATHOLOGY'ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONJC TOXICITY OF META-CRESOL
IN SPRAGUE-DAULEY RATS
Correlation of Gross & Micro Findings
PROJECT ID: MCRESOL GROUP: 50MG/K6 SEX: MALE DAYS; ALL
SAGE 2 FATES: ALL
,NIMAL NO: 3449 • PATHOLOGY ID. NO: 853449 PATHOLOGIST; LHB
ANIMAL FATE: SCHEDULED SACRIFICE
5R08ABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY:
'-LIVER-SLIGHTLY SWOLLEN, PALE, AND LIVER- NECROSIS
RETICULATED
ANIMAL NO: 3450 PATHQLQ6Y ID. NO: S53450 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH: - DAYS ON TEST: 90
=5rY,:TRENCE TO NECROPSY RECORD: RELATED HI STOPATHOLOGY:
>LK^R-SLIGHTLY SWOLLEN LIVER-- CYTOPLASM! C UACUOLATION
ANIMAL NO: 3454 PATHOLOGY ID. NO! 853454 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
=RQBA8LE CAUSE OF DEATH: ' • DAYS CN TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLQ6Y:
>LIUER-MILDLY SWOLLEN > NO COROLLARY CHANGE DETECTED
ANIMAL NO: 3455 PATHOLOGY .ID. NO; 853455 PATHOLOGIST! LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY;
>LIVER-ALL LOBES HOTTLED LIUER- LYMPHOCYTIC INFILTRATE
(Report Continued) 3 1 0
IV-13
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PATHOLOGY ASSOCIATES,. INC'.
STUDY NO. 5221 ,07
SUBCHROMIC TQXIGITY OF META-CRESOL
IN SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Fi&dings
'ROJECT ID; MCRESOL GROUPi 50MG/KG SEX! MALE DAYS: ALL
•AGE 3 FATES: ALL
.NIMAL NO: 3454 PATHOLOGY ID. NOs 85345*6 PATHOLOGIST: LHB
ANIMAL FATE! SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: . DAYS CN TEST: 9Q
REFERENCE TO NECROPSY REC'ORD; RELATED HI STQPATHOLOGY;
•-KIDNEYS-SLIGHTLY MOTTLED KIDNEY- MEPHROPATHY
ANIMAL NO: 3457 PATHOLOGY ID. NOi 853457 PATHOLOGIST; LHB
ANIMAL FATE: SCHEDULED SACRIFICE
3ROBABLE CAUSE OF DEATH; DAYS ON TEST: 90.
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>L?"" "R-PALE AND SWOLLEN SLIGHTLY NO COROLLARY CHANGE DETECTED
(End o-f Report)
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONIC TOX1CITY OF META-CRESQL
IN SPRAGUE-DA14LEY RATS
Correlation o-f Gross & Micro Findings
PROJECT IDs MCSESQL
'AGE 1
GROUP s 50MG/KG
FATES: ALL
SEX; FEMALE
DAYS: ALL
ANIMAL NOs 3571 PATHOLOGY ID. NO; 853571
ANIMAL FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH:
REFERENCE TO NECROPSY RECORD!
>THYMUS-DARK RED MODULE, 2X2 MM,
UENTRAL SURFACE
PATHOLOGIST: LHB
DAYS ON TEST: 90
RELATED HISTOPATHOLOGY:
MEDIASTINAL LN-HEHORRHA5E. THE
NODULE, THOUGHT TO BE PART OF THE
THYMUS, WAS ACTUALLY A MEDIASTINAL
LYMPH NODE.
At- '^L NO: 3573 PATHOLOGY ID. NO; 853573
AN." L FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH;
REFERENCE TO NECROPSY RECORD:
>l (2X2MM) ROUND YELLOW NODULE IN
FAT NEAR LEFT OVARY
PATHOLOGIST! LHB
DAYS ON TEST; ?0
RELATED HISTOPATHCLOGY:
NO COROLLARY CHANGE DETECTED. THE
NODULE DESCRIBED"AT NECROPSY WAS
MOST LIKELY A FOCUS OF FAT NECROSIS.
(End of Report)
IV-15
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221 .07
SUBCHROMIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
ROJECT ID: MCRESOL GROUP: 150MG/KG SEX: MALE DAYS: ALL
AGE 1 FATES: ALL
NIMAL NO: 3478 PATHOLOGY ID. NO: 853478 PATHOLOGIST: LHB
NIMAL FATE; SCHEDULED SACRIFICE
ROBAELE CAUSE OF DEATH: DAYS ON TEST: 90
EFERENCE TO NE.CROPSY RECORD: RELATED HISTOPATHOLOGYs
TESTICLE, LEFT-SOFT AND SMALLER TESTES- ATROPHY,SEMINIFEROUS TUBULES
THAN RIGHT
NIMAL MO: 3479 PATHOLOGY ID. NO: 853479 PATHOLOGIST: LHB
NIMAL FATE: SCHEDULED SACRIFICE
F "-^BLE CAUSE OF DEATH: DAYS ON TEST; 90
.EFbKENCE TO NECROPSY RECORD: RELATED HI STOPATHOLOGY :
LIVER-SLIGHTLY PALE AND SWOLLEN LIVER- CYTOPLASM! C VACUOLATI ON
,NIMAL NO: 3484 PATHOLOGY ID. NO: 853484 PATHOLOGIST: LH3
NIMAL FATE: SCHEDULED SACRIFICE
JROBABL£ CAUSE OF DEATH! DAYS ON TEST: 90
:EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
LIL '--SLIGHTLY SWOLLEN NO COROLLARY CHANGE DETECTED
*> -\ O
O 1 o
IV-16
r.^ ^-.i D .-. f-— ~ I- •!
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPP.AGUE-DAULEY RATS
Correlation o-f Gross. & Micro Findings,
'ROJECT ID: MCRESOL OROUP: 1SOM6/KS SEX; FEMALE DAYS: ALL
AGE i FATES: ALL
iNlMAL NO: 3602 PATHOLOGY ID. MO: 853402 PATHOLOGIST: LHB
,N!MAL FATE: SCHEDULED SACRIFICE
'RQBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHQLOBY:
LIVER-NODULE, 10X12MM, MEDIAN LOBE LIVER- HEPATQDIAPHRAGMATIC NODULE
.MIMAL NO: 3604 PATHOLOGY ID, NO: 853604 PATHOLOGIST: LHB
,NIMAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
JL.' iNCE TO NECROPSY RECORD; RELATED HI STOPATHOLOGY:
•JEJUNUM-MUCOSAL SURFACE DARK RED NO COROLLARY CHANGE DETECTED
(End o-f Report)
IV-17
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAULEY RATS
Correlation o-F Gross & Micro Findings
ROJECT ID: MCRESOL GROUP: 45QMG/KG SEX; MALE DAYS: ALL
AGE 1 FATESs ALL
^IIMAL NO: 3501 PATHOLOGY ID. NO: 853501 PATHOLO.GI ST: LHi
NIMAL FATE: SCHEDULED SACRIFICE
ROBABLE CAUSE OF DEATH: DAYS ON TEST; 90
EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOQY:
LIVER NODULE, 5X5MM, MEDIAN LOBE LIVER- HEPATODIAPHRAGMATIC NODULE
NIMAL NO: 3502 PATHOLOGY ID, NO: 853502 PATHOLOGIST: LHB
MIMAL FATE: SCHEDULED SACRIFICE
CAUSE , OF DEATH: DAYS ON TEST: 90
Er. .sNCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
NIMAL NO: 3503 PATHOLOGY ID. NO: 353503 PATHOLOGIST: LHB
NIMAL FATEs SCHEDULED SACRIFICE
ROBABLE CAUSE OF DEATH: DAYS ON TEST: ?0
EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
NIMAL NO: 3504 PATHOLOGY ID. NO: S53504 PATHOLOGIST: LHB
NIMAL FATE: FOUND DEAD
ROBABLE CAUSE OF DEATH: DAYS ON TEST: 4
EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
I 1 RED MOTTLED LUNG- CONGESTION
PALE LIVER PALE COLOR DUE TO MILD PM AUTOLYSIS.
BLOOD IN THE THORACIC CAVITY (TISSUE UNAVAILABLE)
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PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
•IN SPRAGUE-DAWLEY RATS
Cor-relation o-f Gross & Micro Findings
ROJECT ID: MCRESOL 6ROUP: 45QMG/KG SEX: MALE DAYS; ALL
AGE 2 FATES: ALL
iNIMAL NO: 3S05 PATHOLOGY ID. NO: 8S3S05 PATHOLOGIST: LH8
MIMAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
:EFERENCE TO NECROPSY RECORD-. RELATED HISTCPATHOLOGY:
•NGL
iNIMAL NO: 3506 PATHOLOGY ID. NO: 8535Q6 PATHOLOGIST! LHB
NGL
ANIMAL NO: 3508 PATHOLOGY ID, NO: 853503 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
5ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLCGY:
>LIVER-SL1GHTLY SWOLLEN ' THE CAUSE OF THE SWOLLEN APPEARANCE
OF THE LIVER WAS NOT DETERMINED.
31G
(Report Continued)
IV-19
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221,07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAUILEY RATS
Correlation o-f Gross &. Micro Findings
'ROJECT ID: HCRESOL GROUP: 450MG/KG SEX: MALE DAYS: ALL
*AGE 3 FATES: ALL
ANIMAL NO: 3509 • PATHOLOGY ID. NO: 853509 PATHOLOGIST; LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH! DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHQLQGY:
-•RT. TESTIS-SLIGHTLY ENLARGED. THE TESTIS SHOWING SOME ATROPHY IN
THE SEMINIFEROUS TUBULES IS THE
LARGER OF THE TWO TESTES. WHILE
MOST TUBULES SHQy ADEQUATE
SPERMATOGENESIS, ALL TUBULES ARE
MILDLY DILATED.
¥-1? "L NO: 3510 PATHOLOGY ID. NO: 853510 PATHOLOGIST: LHB
^ts\ ,L FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH: • DAYS ON TESTs 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGYs
>NGL • ••..-'•-:•
ANIMAL NO: 3511 . PATHOLOGY ID. NO: 353511 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 9Q
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
7
-------
PATHOLOGY ASSOCIATES, INC.
STUDY MO. 5221 ,07
SUBCHRONIC TOX1CITY OF META-CRESOL
IN SPRAGUE-DAULEY RATS
Correlation of Gross & Micro Findings
PROJECT ID: MCRESOL 8ROUP: 4SQMQ/KG SEX: MALE DAYS: ALL
PAGE 4 ' FATES: ALL
ANIMAL NO: 3512 ' PATHOLOGY ID. NO: 853S12 PATHOLOGIST: LHS
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY;
>NGL
ANIMAL NO: 3513 PATHOLOGY ID. NO: 853513 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH:' • . DAYS ON TEST: 90
RPERENCE TO NECROPSY RECORD: RELATED "HISTOPATHOLOGY:
ANIMAL NO: 3514 PATHOLOGY ID. NO: 853514 - • PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: • DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: ' RELATED HISTQPATHOLOSY:
>NCL
ANIMAL NO: 3515 PATHOLOGY ID. NO: 853515 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued) ,, . o
i'j 1 O
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRCM1C TOXIC ITY OF META-CRESOL
.IN SPRAGUE-OfiULEY RATS
Correlation o-f Gross & Micro Findings
ADJECT ID: MCRESOL GROUP; 450MG/Ke SEX: MALE DAYS: ALL
5 FATES: ALL
^IIMAL NO: 3514 . PATHOLOGY ID. NO: 853514 PATHOLOGIST: LHB
^IMAL FATE: SCHEDULED SACRIFICE
30BAELE CAUSE OF DEATH: • DAYS ON TEST: 90
EFERENCE TO NECROPSY RECORD: RELATED HI STOPATHOLOGY:
•4GL
-tlMAL NO: 3517 • PATHOLOGY ID. MO: 853517 PATHOLOGIST! LHB
•HMAL FATE: SCHEDULED SACRIFICE
30BABLE CAUSE OF DEATH: , DAYS ON TEST: 90
EFERENCE TO NECROPSY RECORD! RELATED HISTOPATHOLOBY:
^JIMAL MO: 3518 PATHOLOGY ID. NO: 853518 PATHOLOGIST; LHS
^ilMAL FATE: SCHEDULED SACRIFICE
ROSABLE CAUSE OF DEATH: DAYS ON TESTs 90
EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
RIGHT KIDNEY SLIGHTLY MOTTLED THE CAUSE OF THE MOTTLING IN THE
RIGHT KIDNEY WAS NOT DETERMINED.
•IIMAL NO: 3519 PATHOLOGY ID. NO: 853519 PATHOLOGIST: LHB
NiMAL FATE: SCHEDULED SACRIFICE
ROBABLE CAUSE OF DEATH: " DAYS ON TEST: 90
EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOCY:
NGL
(Report Continued)
IV-22
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONIC TOXICITY OF META-CRESQL
IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
5ROJECT ID: MCRESOL GROUP: 450MG/KG SEX: MALE DAYS; ALL
AGE 6 FATES: ALL
,N!MAL NOs 3520 ! PATHOLOGY ID. NO; 853520 ' PATHOLOGIST! LHB
iNIMAL FATEs SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: DAYS ON TESTi *0
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY:
'NGL
(End of Report)
IV-23
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO, 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAUILEY RATS
Correlation o-f -Gross & Micro Findings
'ROJECT ID: MCRESQL GROUP: 450HG/KG SEX: FEMALE DAYS; ALL
'AGE 1 FATES: ALL
WIMAL NO: 3631 PATHOLOGY ID, NO: 953631 PATHOLOGIST: LHB*
ANIMAL FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH; DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATKOLOGY:
>UTERIME HORNS-DILATED, FLUID FILLED UTERUS- DILATATION
ANIMAL NO: 3632 PATHOLOGY ID. NO: 853632 PATHOLOGIST: LHB
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 8?
Ru. .ENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>KIDNEY-i <1X1HM) ROUND INDENTATION THERE IS NO APPARENT INDENTATION OR
IN CORTEX OF RIGHT KIDNEY OTHER LESION IN THE KIDNEY WHICH
WOULD CORRELATE TO THE INDENTATION
NOTED AT NECROPSY,-
ANIMAL NO: 3633 PATHOLOGY ID, NO: 353633 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATHi DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY;
>NGL
(Report Continued)
IV-24
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
'ROJECT ID: MCRESOL GROUP; 450MG/KB SEX: FEMALE DAYS: ALL
•AGE 2 FATES: ALL
,NIMAL MO: 3434 PATHOLOGY ID. MO: 853634 PATHOLOGIST: LHB
*N1MAL FATE; SCHEDULED SACRIFICE
•ROSABLE CAUSE OF DEATH: '• DAYS ON TESTi 90
REFERENCE TO NECROPSY RECORD! RELATED HISTOPATHOLOGYs
•NGL
,NIMAL NO: 3635 ' PATHOLOGY ID. NO: 853635 PATHOLOGIST: LHB
iNIMAL FATE! SCHEDULED SACRIFICE
-JROBABLE CAUSE OF DEATH:. DAYS ON TEST: 90
TO NECROPSY RECORD: RELATED HISTQPATHQLOGY:
ANIMAL NO: 3636 • PATHOLOGY ID. NO* as343N6L
ANIMAL NO: 3637 PATHOLOGY ID. NO: 853437 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATHi DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NOL
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221 .07
SUBCHRONIC TOXIC1TY OF META-CRESOL
.IN SPRAGUE-OAWLEY RATS
Correlation o-f Gross & Micro Findings
ROJECT IDs MCRESOL GROUP: 45QMG/KG SEX; FEMALE . DAYS; ALL
A8E 3 FATES; ALL
NIMAL NO: 3638 PATHOLOGY ID. NO: 353638 PATHOLOGIST; LH8
M1MAL FATE! SCHEDULED SACRIFICE
ROBABLE CAUSE OF DEATH; DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHCLOGY:
KIDNEY-i (3X3MM) CYST IN CORTEX OF KIDNEY- CYST
LEFT KIDNEY
.NIMAL NO; 3639 ' PATHOLOGY ID. NO: 953439 PATHOLOGIST: LHB
.NIMAL FATEs SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: . DAYS ON TEST: 90
V '"' "ENCE TO NECROPSY RECORD: RELATED HISTOPATHQLOGY:
>MGL
ANIMAL NO: 3440 PATHOLOGY ID. NO: 853440 PATHOLOGIST! LHB
ANIMAL FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATHi DAYS ON TEST s 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
AN IHAL NO: 3641 PATHOLOGY ID. NO: 853441 PATHOLOGIST; LHB
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
'-> 9 Q
(Report Continued) «-- ~ ^
TV ?fi
-------
PATHOLOGY ASSOCIATES, INC,
: STUDY NO. 5221.07
SU8CHRONIC TOX1CITY OF META-CRSSOL
.IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Hicro Findings
"RCJECT ID: MCRESOL GROUP; 450MS/K6 SEX: FEMALE DAYS: ALL
AGE 4 FATESi ALL
ANIMAL MO; 3A42 PATHOLOGY ID. NO: 353NGL
ANIMAL MO: 3645 PATHOLOGY ID. NO: 853,545 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
='ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY!
:-NGL
3 >i- 4
IV-27
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PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONIC TOXICITY OF META-CRE3QL
IN SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
'ROJECT ID: MCRESOL GROUP: 45QMG/KG SEX: FEMALE DAYS: ALL
>AGE 5 FATES; ALL
,NIMAL NO: 3646 PATHOLOGY ID, NO: 853646 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
^ROBABLE CAUSE OF DEATH: , DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGYJ
>NGL
ANIMAL NO: 3647 PATHOLOGY ID. NO; 353647 PATHOLOGIST: LHB
,NIMAL FATE: SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: DAYS ON TEST! 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
-iNIMAL NO: 3648 PATHOLOGY ID. NO: 853648 PATHOLOGIST: LHB
ANIMAL FATEs SCHEDULED SACRIFICE
'ROBABLE CAUSE OF DEATH: DAYS ON TESTs 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3649 PATHOLOGY ID. NO: 853649 PATHOLOGIST: LHB
ANIMAL FATE: SCHEDULED SACRIFICE
=ROBABLE CAUSE OF DEATH: DAYS ON TEST: 90
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
f y j-k
-------
PATHOLOGY ASSOCIATES, INC.
STUDY NO. 5221.07
SUBCHRONIC TQXICITY OF META-CRESOL
IM SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
ROJECT ID: MCRESOL GROUP! 450MG/KG SEX: FEMALE DAYSi ALL
AGE 6 FATES; ALL
N1MAL NO: 3,650 PATHOLOGY ID. NO: 853450 PATHOLOGIST: LHB
MIMAL FATE: SCHEDULED SACRIFICE
ROBABLE CAUSE OF DEATH: DAYS ON TEST: 70
.EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOBY:
NGL
(End o-f Report)
326
IV-29
-------
GROSS AND MICROSCOPIC FINDINGS
Interim Sacrifice
MALES
3401
3434
3435
HQ32LSJL Gross Observation
O.OmgAg Kidneys mottled slightly
5Qmg/kg; Kidney, right-small, tan
nodule, 0.1x0.1cm
50mg/kg Kidney, right-small, tan
nodule, 0.1x0,1cm
Kidney, left-two, sma',1
tan nodules, 0.1x0.1cm
3439 SQmg/lcg Kidneys-slightly mottled
3466
3496
Hiproscop ic Observation
Normal-No corresponding lesion
Normal-No corresponding lesion
Note The kidney lesion was not
found at trim.
Nephrooathy, focal, mild
Comment: The nephropathy In
the right kidney wes actually a
slight indentation.
Comment: Nodules wirs not
noted on either kidney. No
corresponding lesions were
noted in the left kidney,
Infarct, chronic, focal, mild
Hemorrhage, focal, mild
Nephropathy, minimal
ISQmg/kg Kidneys-mottled slightly Nephropathy, minimal
450mg/kg Lungs-multiple foci on
all lobes, 0.1 cm
Lyrnphotytic infiltrate, multifccal,
moderate
Inflammation, interstitial, multifocal,
mild
'.> 9 7
»J t* '
IV-30
-------
GROSS AND MICROSCOPIC FINDINGS
Interim Sacrifice
FEMALES
Animal Mo. Dosa.Gp. Gross Observation
3534 0,0mg/kg Spleen-mottled
3569 50mg/kg Kidney, right-small
amount of white fluid
cams out of kidney when
scored.
3593 150mg/kg Kidney, right-pelvis
dilated slightly
3624 450mg/V
-------
V QUALITY ASSURANCE REPORT
329
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QUALITY ASSURANCE STATEMENT
This histopathology project has been conducted in compliance with Good
Laboratory Practice regulations promulgated by the U.S. Food and Drug
Administration and the U.5. Environmental Protection Agency. Pathology
Associates, Incorporated has a functioning and responsive quality
assurance unit which has conducted appropriate inspections and reported
all findings to management. The following is a record of those inspections
and reports:
Date Findings Reported
Date of to Management
Inspection' Phase Inspected and Study Pathologist.
**01-02-86 Necropsy 01-03-86
* 01-07-86 Tissue Trimming 01-09-86
* 01-09-86 Processing 01-14-86
* 01-09-86 Embedding 01-14-86
* 02-19-86 Microtomy 02-19-86
* 02-19-86 Staining 02-19-86
* 02-19-86 Coverslipping 02-19-86
**02-IO-B6 Labeling 02-10-86
**03-M-86 ' Individual Animal Data 03-21-86
**03-M-86 Data Entry . 03-21-86
**03-18-86 Computer Validation 03-21-86
**Q3-20-86 Draft Pathology Report 03-21-85
**04-01-86 Final Pathology Report 04-01-86
* General monthly phase inspection
** Inspection specific for Study Number
'In accordance with the PA1 Quality Assurance Division's Standard Operating
Procedures, phase inspections are routinely conducted on a random basis at a
minimum of monthly. Dates of inspection are reported for each study
according to the most recent phase inspection conducted during that period.
G.
April 01, 1986
' Director, Quality Assurance Unit Date
Study Number: 5221.07, "Subchronic Toxicity Study of Meta-Cresol in
Sprague Dawley Rats."
'.? 9
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APPENDIX 1
REPORTS CODE TABLE
-------
PATHOLOGY ASSOCIATES, INC.
STUDY MO, 5221,07
SUBCHRONIC TOXICITY OF META-CRESOL
IN SPRASUE-DAWLEY RATS
Reports Code Table
N Tissues within normal histological limits
A Autolysis prtcluding adequate evaluation
U Tissues unauai1ab!e/unsuitabl e for evaluation
S Tissues not applicable to anim-a!
* Tissues not examined/fiat required by protocol
i m i nimal
2 mMd
3 moderate
4 severe
) focal
] diffus*
> mul t i -focal
P Present
8 Neoplasm, Benign
H 'Neoplasm, Malignant without Metastasis
C Neoplasm, Malignant with Metastasis
X Metastatic SI te (•*•)"
-------
APPENDIX 2
ABBREVIATION LIST
-------
ABBREVIATION LIST
INFLAMMATION
PARS' DiSTAUS
PER I VASCULAR
PROLIFERATION
VACUOLiZATION
I NFL AM.
PARS DIST.
PERiV.
PROL1F.
VACUO.
'-* ^ 4
i!
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|