Document 1059754

TABLE A2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE RATS : LOW DOSE
(Continued)
WEEK
STUDY
0
8
9
4
9
0
0
9
1
0
9
2
0
9
3
0
9
4
0
9
4
0
9
4
0
9
5
0
9
5
5
5
3
5
--
5
2
5
1
6 ' 1
2
3
4
2
2
4
0
4
2
3
3
5
0
3
.
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
i-
'+
+
M
+
+
+
+
+
+
+
+
+
+
+
+
0
3
0
0
3
8
0
5
6
0
6
2
0
6
2
0
6
7
0
7
0
0
7
7
0
7
8
0
8
3
0
8
4
0
8
6
~ 7
a 1
4
1
5
5
3
1
4
2
7
5
9
5
9
4
8
4
4
4
9
9
4
3
6
3
+
+
+
+
+
+
+
+
+
+
+
+
+
-h
~ I~3
f
M
M
M
+
+
+
+
+
X
+
X
R4
+
+
+
.+
+
+
+
-F
+
+
+
+
+
+
CARCASS
ID ,
GENITAL SYSTEM
Coagulating gland
Epididymis
Leukemia mononuclear
Mesothelioma malignant, metastatic .
Penis
Leukemia mononuclear
Prepntial gland
Adenoma
Carcinoma
Leukemia mononuclear
Prostate
Adenoma
Leukemia mononuclear
Serosa, mesothelioma malignant,
metastatic
Seminal vesicle
Leukemia mononuclear
Semsa, mesothelioma malignant,
f
p
t
metastatic
Testes
Leukemia mononuclear
Bilateral, interstitial cell, adenoma
Interstitial cell, adenoma
'Punic, mesoChelioma malignant
HEMATOPOIETIC SYSTEM
Blood
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lymph node
Bronchial, leukemia mononuclear
Deep cervical, leukemia mononuclear
Iliac, leukemia mononuclear
Inguinal, leukemia mononuclear
Lumbar, leukemia mononuclear
Nledias2inal, histiocytic sarcoma,
meCastatic
Mediastinal, leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, mandibular
Leukemia mononuclear
Lymph node , mesenteric
Leukemia mononuclear
Mesothelioma malignant, metastatic
0
9
8
0
8
8
0
~ 1
3
+
i-
+
-i-
R
+
+
-e-
+
+
+
+
+
.. .
+
+
+
+
x
,-
+
i-
X
+
+
+
+
+
-F
.+
+
+
+
+
+
+
X
X
X
+
+
+
+
+
X
+
R
+
X
:i
R
%
R
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
+
X
+
+
X
+
X.
+
+
..
.
+
X
ft
+
%
'r
X
+
. - +
X
x
X
IC
x
+
+
.X
+
+
+
+
X
+
%
+
X
+
%
+
%
+
R
+
M
-d-
+
+
R
R
+
+
+ . M
+
+
R
X
R
+
+
+
+
+
%_
+ +
%
+ +
R
+
+
X
+
+
X
_
+
t
R
t
+
X
+
+
+
+
R
+
+
%
+
+
X
+
%
-
Spleen
Leiomposarcoma, metastatic, intestine
sma11
Leukemia mononuclear
Capsule, mesothelioma malignant
Capsule, mesothelioma malignant,
raetastatic
Thymus
Leukemia mononuclear
TFI"CEGUAh I3"PARY Y T
Mammary gland
Skin
Hasosquamous tumor malignant
Subcutaneous tissue, fibaoma
Subcutaneous tissue, fibrosarcoma
Subcutaneous tissue, histiocytic
sarcoma
Subcutaneous tissue, leukemia
mononuclear
Subcutaneous tissue, lipoma
Subcutaneous tissus,liposarcoma
MUSCU
Bone
Skeletal muscle
Laiomposarcoma, metastatic, intestine
small
NERVOUS SYSTE
Brain
Leukemia mononuclear
Meninges, leukemia mononuclear
Meninges, cerebrum, histiocytic
sarcoma, metastatic
Peripheral nerve
Spinal cord
Leukemia mononuclear
Meningas, leukemia mononuclear
I-iydroquinone,NTP `PR 366
+
+
+
+
+
+
T
+
+
+
+
+
X
+
+
+
+
+
+
+
+
+
+
+
+
A
+
+
R
X
+
+
+
R
M
+
M
+
+
+
+
X
+
X
+
+
+
+
+
+
-h
X
X
+
i-
X
M
+
-fr
X
+
+
X
x
+
%
+
X
.
+
+
X
+
X
A
R
+
+
+
+
X
+
+
+
+
+
+
X
X
X
'
+
X
+
X
R
+
R
+
X-
+
R
+
X
+
+
+
%
X
R.
+
+
. +
t
+
R
X
+
+
M
+
M
+
+
X
+
+
+
x
+
+
+
R
+
R
+
x
+
+
-F
x
+
M
+
R
+
x
+
+
M
+
M
+
+
+
\4
M
+
+
+
YvI
+
+
+
+
+
+
+
+
+
t
.
+
.
+
.
+
+
M
+
+
+
+
+
+
+
+
+
+
+
+
-F
+
+
+
+
+
+
+
+
+
+
+
+
A
X
+
x
+
X
+
X
X
x x x
x
,
+
R
R
+
+
+
+
+
+
+
-h
+
+
+
+
+-
.
%
+
+
+
+
+
+
+
+
+
+
.
+
+
+
X
106
+
+
i-
+
+
+
t
.
+
.
R
+
+
+
+
+
R
R
x
+
+
+
+
i-
+
..
X
A
TABLE t12 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE RATS: LOW DOSE
(Continued)
wE~xs N
STUDY
CARCASS
ID
Coa~tang gland
Egi~idymis
--60 0
0
1
1
1
1
1
a
i
a.
t
0
5
i
0
5
i
i
0
0
5 . 5
~
0
5
i
0
5
i
0
5
a
0
5
i
0
5
i
0
5
1
0
5
i
0
5
7
4
3
4
9
2
3
3
4
1
9
1
2
1
5
4
6
3
7
3
8
3
0
2
1
2
3
2
4
`3
4
4
6
2
6
1
7
2
8
1
4
+
+
+
9
6
9
7
9
8
2
2
6
4
4
5
+
Leukemia mononuclear
Mesothelioma malignant, metastatic
+
4
1
8
9
+
.
0
2
-F
0
2
+
oma
Carcinoma
Leukemia mononuclear
Prostate
Adenoma
Leukemia mononuclear
Serosa, mesotheLioma malignant,
metastatic
Seminal vesicle
Leukemia mononuclear
Serosa, mesothelioma malignant,
matastatic
Testes
Leukemia mononuclear
+~
+
+
+
+
i-
Blood
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lymph node
Bronchial, leukemia mononuclear
Deep cervical, leukemia mononuclear
Iliac, leukemia mononuclear
Inguinal, leukemia mononuclear
Lumbar, leukemia mononuclear
Mediastinal, histiocytic sarcoma,
metasta4.ic
2vIediastinal , leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, maadibular
Leukemia mononuclear
-Lymph node, mesenteric
Leukemia mononuclear
iesothelioma malignant, metastatic
Spleen
Leiomposarcoma, metastatic, intestine
sma11
Leukemia mononuclear
Capsule, mesothelioma malignant
Capsule, mesothelioma malignant,
metastatic
Thymus
Leukemia mononuclear
X
+
0
4
.
0
2
+
,
.
..
-1 - 1
0
5
8
2
.
.
X
%
-a
-h
+
+
+
+
x
+
"'r
.
+
i-
+
t
t
+
+
+
+
+
.
t
+
A:
7C
R
X
X
+
-i-
+
X
+
+
i-
I-
+
X
+
X
+
+
+
+
X
+
X
+
R
Bilateral, interstitial cell, adenoma
Interstitial cell,adenoma
Tunic, mesothelioma malignant
X
X
R
+
X
+
X
r
R
x
+
+
+
+
+
X
t
t
i-
X
x
+
+
+
+
dR
+
+
+
+
+
+
+
-i-
,
t
R
X
t
+
X
X
-F
X
t
t
i-
.
X
R
X
%
+
X
+
X
+
t
-~
+
+
X
+
+
X
+
X
+
+
+
X
+
X
+
f
+
+
+
%
7L
X
+
X
+
7C
+
+
+
+
+
K
+
X
+
+
+
+
+
+
+
X
X
+
+
X
+
X
+
X
+
+
R
X
.
+
+
+
i-
X
+
X
+
+
+
X
i-
+
R
+
K
M
+
+
.
1s"
+
X
+
i-
+
+
+
+
+
+
+
-r
+
.
+
+
+
+
+
-t-
+
+
+
+
+
+
,-
+
+
+
M
+
+
+
X
A
X
M
M
+
+
+
+
+
+
.
t
+
+
+
+
+
X
X
X
X
.
-F
E'
R
g
-
Bone
t
X
X
R
K
+
+
+
+
X
t
X
+
X
X
R
+
+
X
.
Mammary gland
Skin
BasosquamoUS tumor malignant
Subcutaneous tissue, fibmma
Subcutaneous tissue, fbrosarcoma
Subcutaneous tissue, histiocyCic
sarcoma
Subcutaneous tissue, leukemia
mononuclear
Subcutaneous tissue, lipoma
Subcutaneous tissue, lipGsarcoma
Leukemia mononuclear
A2eniages, leukemia mononuclear
Meaiages, cerebrum, histiocytic
sarcoma, meEastatic
Peripheral nerve
Spinal cord
Leukemia mononuclear
Moninges,leukemia mononuclear
0
4
0
4
x
Leukemia mononuclear
Brain
0
4
4
Penis
Skeletal muscle
Leiomyosarcoma, metastatic, intestine
small
0
3
t
+
X
X
107
+
+
+
+
t
t
-h
t
.
.
t
.
'
Hydroquanone, NTP TR, 366
TABLE E12 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE : RATS : LOW DOSE
(Continued)
WEEKS
STUDY
N
I
0
5
CARCASS
ID
GENITAL SYSTEM
Coag¢lating gland
Epididymis
Leukemia mononuclear
.
MYesothelioma malignant, metastatic'
Penis
Leukemia mononuclear
Prepvtial gland
Adenoma
Carcinoma
Leukemia mononuclear
Prostate
Adenoma
Leukemia monoauclear `
Serosa, mesothelioma malignant,
metastatic
Seminal vesicle
.
Leukemia mononuclear
Serosa, mesothelioma malignant,
meEastatic
Testes
Leukemia mononuclear
Bilateral, interstitial cell, adenoma
Interstitial cell, adenoma
Tunic, mesotbelioma malignant
_Z
0
5
I
iJ
5
a. ,
0
0
5
5
-2- 2
1
5
1
1
'
5
2
2
5
3
,
TOTAL:
TISSUES
TUMORS
2
6
2
37
+
R
1'
1
34
_
1
41
~
+
'
+
+
+
-+
+
R
R
R
X
R
.
,
_
54
9
36
13
'
R
HEMATOPOIETIC SYSTEM
Blood
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
1'
36
.6 .,
,
+
25
%
Lymph node
Bronchial, leukemia mononuclear
Deep cervical, leukemia mononuclear
Iliac, leukemia mononnciear
Inguiaal, leukemia mononuclear
Lumbar, leukemia mononuclear
Mediastinal, histiocytic sarcoma,
37
14
.
+
41
-
metastatie
Mediastinal, leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, mandibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
MesotheIioma malignant, metastatic
Spleen
Leiomyosaxcoma, meCastatic, intestine
small
Leukemia mononuclear
Capsule , mesothelioma malignant
Capsule, mesothelioma malignant,
metsstatic
Thymus
Leukemia mononuclear
7
+
+
+
X
+
M
M
+
+
X
38
14
3$
15
t
52
x
1
26
-
.
35
15
+
X
INTEGUMENTARY SYSTEM
Mammary gland
Skin
Basosqvamous tumor malignant
Subcutaneous tissue, fibroma
Subcutaneous tissve,fibrosarcoma
Subcutaneous tissue, histiocytic
sarcoma
Subcutaneous tissue,leukemia
mononuclear
Subcutaneous tissue, lipoma
Subcutaneous tissue,liposarcoma
U
KE
L
29
37
1
E
37
Bone
Skeletal muscle
Leiomyosarcoma, metastatic, intestine
small
1
NERVOUS SYSTEM
Brain
Leukemia mononuclear
Menfinges, leukemia mononuclear
Meniages, cerebrum, histiocytic
sarcoma, metastatic
Peripheralnerve
Spinal cord
Leukemia mononuclear
Meniages, leukemia mononuclear
Hydroquincane, NTPTR 366
37
I
108
13
TABLE A2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE RATS: LOW DOSE
(Continued)
WEEKS
STUDY
N
CARCASS
ID
Lung
Carcinoma, metastatic, Zymbal gland
Histiocytic sarcoma, metastatic
Leukemia monoauclear
Liposarcoma, metastatic, skin
Nose
Leukemia mononuclear
Trachea
0
1
3
0
3
0
0
3
8
0
5
6
0
6
2
0
6
2
00
6
7
7 0
0
7
7
0
7
8
0
8
3
0
8
4
0
8
6
0
8
8
0
8
8
0
8
9
0
9
0
0
9
1
0
9
2
0
9
3
0
9
4
0
9
4
0
9
4
00
9
9
5
5
7
1
4
1
5
5
3
1
4
2
7
5
9
5
9
4
6
4
4
4
9
3
4
3
6
3
5
3
5
5
5
2
5
1
6
2
1
3
4
2
2
4
0
4
2
3
3
5
0
3
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+,
+
+
+
+
+
+
+
%
R
%
X
X
X
X
+
+
+
+
+
+
+
X
+ .+
+
+
+
X
+
t-
.
+
+
+
+
-I-
+
+
+
+
+
+
+
. . .
+
+
K
+
+
+
%
+
+
+
R
+
Ear
Eye
Hazderian gland
Zymbal gland
Adenoma
Carcinoma
URINARY SYSTEM
Kidney
Leukemia mononuclear
Capsule, .mesotbelioma maligaant,
metastakie
Renal tubule, adenoma
Urinary bladder
Leukemia mononuclear
Serosa, mesothelioma malignant,
metastatit
TransiEional epithelium, carcinoma,
papillary
+
R
+
%
+
.R
%
X
t
+
R
+ . +
+
+
X
+
+
R
+
%
+
+
R
+
R
+
+
+
t
+
+
+
X
+
+
;-
+
+
+
+
X
+
X
+
+
X
+
+
+
X
+
A
+
+
-t-
+
R
+
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
x
+
+
+
+
+
+
X-
R
.
X
109
H;rdroquinone, NTP TR 366
TABLE A2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE RATS: LOW DOSE
(Continued)
,
1
1
1
_1
_
1 1 1
0
0
0
1
0
WEEK ta
9 9 9 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 05 05 05
STUDY "
2
2
3
4
4
4
4
5
5 5
5 5
5
5
CARCASS
ID
RESPIRATORY SY
Lung
Carcinoma, metastatic, Zymbal gland
FSistiocytic sarcoma, metastatic
Leukemia mononuclear
Liposarcoma, metastatic, skin
Nose
Leukemia mononuclear
Trachea
Car
Eye
Harderian gland
ZymbaI gland
Adenoma
Carcinoma
SYSTEM
6
7
8
9
1
2
2
6
4
4
5
7
4
3
4
9
2
3
3
4
1'
+
+
+
-f-
+
+
X
X
+
4
+
+
R
+
+
-
.
ARY SYSTEM
Kidney
Leukemia mononuclear
Capsule, mesothelioma malignant,
tastatic
Renal
me tubule, adenoma
Urinarybladder
Leukemia mononuclear
Serosa, mesothelioma malignant,
metasCatic
Transitional epithelium, carcinoma,
papillary
I3ydroquinone, NTP TR 366
. .
. .
+
° X
X
t .. +. . t
+
.
+
+
+
+
+
9
1
2
1
5
4
6
3
+
+
+
+
k . +
+
+
+
+
+
-t-
+
+
-
8
3
0
1
0
2
1
2
3
2
4
3
4
4
6
2
+
R
'
.
+
+
7
3.
1
1
1
5
5
5 .
7
2
8
1
8
2
0 0 0
6
1
.
-
.
+
.
X
X
.
+
+
+
Y
tR
+
+
A
+
%
+
+
.
+
X
iR
+
.
+
+
X
.
+
R
+
R
+
+
+
+
+
110
+
X
+
+
,
+
.
+
+
-
+
+
- R
+
x
+
%
.
+
..
+
X
R
-
+
X
,
LOW DOSE
TABLE A2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY (1F MALE RATS :
(Continued)
wEExs rr
STUDY
CARCASS
ID
x
r
0
5
i
0
5
7.
1
ii
Q
5
5
1
5
2
0
5
0
5
5
3
6
1
TOTAL:
TISSUES
TUMORS
38
Lung
Carcinoma, metastatic, Zymbai gland
Histiocytic sarcoma, metastatic
Leukemia mononuclear
Liposarcoma, metastatic; skin
Nose
Lenkamia mononuclear
Trachea
.
.
,
.
.,
. ,
. ,
. . . .
.
:
.
.
.
.
.
.
.
-
.
.
.
37
. 11 .
37
,
2
3
2
4
I
3
Ear
Eye
Harderian gland
Zymbal gland
Adenoma
Carcinoma
Kidney ~-~
Leukemia mononuclear
Capsule, mesothelioma malignant,
metastatic
.
Renal tubule, adenoma
Urinary bladder
Leukemia mononuclear
Serosa, masothelioma malignant,
meCastatic
Transitional epithelium, carcinoma,
papillary
. ..
1
17I
+
+
+
+
.
x
55
22
,
1
4
- 37
4
2
1
g1~
Hyiiroquinone, N'PP TR, :366
.
.
.
.
_
.
..
OF MALE RATS IN THE TWO-YEAR GAVAGE
TABLE A2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY
STUDY OF HI'IDROQ(TINONE : HIGH DOSE
WEEKS
STUDY
N
CARCASS
ID
Esophagus
Intestine large
Intestine large, cecum
Intestine large, colon
Intestine large,rectum
Intestine small
Intestine small, duodenum
Leukemia mononuclear
Intestine small, ileum
Leukemia mononuclear
Intestine small,jejunum
Liver
4
6
0
6
8
0
7
2
0
7
5
8
0
0
8
0
0
8
1
0
8
3
0
8
6
0
8
8
0
8
7
0
8
7
0
8
8
0 Q
8 9
8, 1
0
9
1
0
9
2
0
9
3
0
9
3
0
9
5
0
9
6
0
9
6
0
9
6
0
9
6
0
9
7
7
5
7
4
6
5
8
5
0
6
9
4
0
4
5
4
5
3
8
4
9
4
4
5
9
.3
0
3
4
4
8
3
1
5
9
3
6
4
2
3
7
2
8
3
7
3
8
2
+
+
+
+
+
+
+
++
.
+
+
+
±
+
+
+
+
+
+.
+
+
+
+
+
M
+
+
°
.
Hepatocellular adenoma
Histiocytic sarcoma
Leukemia mononuclear,
Neoplastic nodule
+
+
+
+
+
+
+
+
+
+
+. +
+ +
+ +
+ +
+ +
+
+
+
+
A
A
+
+
+
+
-F
+
+
+
A . +
+
A
+
+
+
+
+
+
+.
+
+.
+
i-
+
-F.
A
.+
+ -F
. .. .
X
R
X
X
R
Ps
+
+
+
+
+
+
+
i+
+
+
+
.
Mesentery
Leukemia mononuclear
Mesothelioma malignant
Pancreas
Leukemia mononuclear
Mesothelioma malignant
Salivary glands
Leukemia mononuclear
Stomach
Stomach, forestomach
Mesothelioma malignant
Stomach, glandular
Levkem :a mononuclear
Tooth
Pulp, leukemia mononuclear
.
.
Schwannoma, NOS
_s'1`E
Adrenal gland
Adrenal gland, cortex
Leukemia mononuclear
Adrenal gland, medulla
LBukemiamononuclear
Pheochromocytoma malignant
Pheochromocytoma benign
Bilateral, pheochromocytoma benign
.
Islets, pancreatic
Parathyroid gland
mononuclear
Leukemia
Pituitary gland
Leukemia mononuclear
Pars distalis, adenoma
Thyroid gland
Leukemia mononuclear
C-cell, adenoma
Gcell, carcinoma
Follicular cell,adenoma
-F
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
.
+
.
+
+
+
+
+
+
-
X
X
+
+
+
-F
+
+
+
-t-
+
.
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-F
+
+
+
+
+
+
+
+
+
+
Coagulating gland
Leukemia moaonuclear
Epididymis
Leukemia mononuclear
Mesothelioma malignant
Prepvtia! gland
Adeaoma
Carcinoma
Leukemia mononuclear
Prostate
mononuclear
Leukemia
Seminal vesicle
Leukemia mononuclear
Testes
Leukemia mononuclear
Bilateral, interstitial cell, adenoma
Interstitial cell, adenoma
Tunic, mesothe3ioma malignant
Hydroquinone, NTP TR. 366
R
++
+
+
+
+
+
+
+
i-
.. .
A
+
+
+
+
+
+
+
+
+
+ .
+
+ +
. . . +
+ ++
+ + +
+ + +
R
.
-F
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ ~
+
+
+
+
+
+
+
+
A
. .. .
+
+ +
, +
+ +
.. .
+
+
+
A
+
+
,X
R
%
%
X
+
+
+
+
+
+
+
+
X
X
R
+
+
+
+
+
+,
+
+
X
+
+
+ _ +
+
+
+
+
+
+
+
+
+
+
+ - +
+
+
+
+
+
+
+
+
+
±
+
+
+
+
+
+
+
+
+
+
+
+- +
+ +
+
+
+
+
+
+
+
+
+
+
+
+
++
+
+
i-
+
+
+
+
+
+
+
+.
+
+
+
+
+
+
+
+
+
+
+
X
+
X
+
+
X
+
X
+
+
+
+
R
+
R
+
+
+
+
+
+
+
+
R
+
+
+
+
+
+
+
+
R
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
R
+
R
+
+
+
+
-t-
+
+
a+
+
+
+
+
+
+
+
+
'
+
+
+
+
+
+
+
+
X
R
+
+
+
.
a
+
.
+
+
+
+
+
+
+
+
X
+
X
+
+
A
+
X
+
+
X
+
X
+
+
X
+
%
+
+
+
+
+
7C
+
X
+
+
+
+
X
+
+
+
+
+
+
+
+
X
+
+
+
+
+
+
+ +
+ A
+ +
+
+
+ +
+ ,+
+ +
+ +
X
X
+
_
-
None
+
, +'
+
-
t
+
+
+
+
+
+
+
`
X
Heart
Leukemia mononuclear
8
4
%
.
+
+
X . %
R
+
+
X
+
X
+
+
R
%.XR R
+
-
X
X
+
+
X
X
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
M
+
+
.
+
+
R
+
+
%
+
R
+
.
+
+
+
+
X
M
+
+
+
+
+
x
+
+
+
%
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t-
+
,
¢
+
i-
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+ . +
+
+
+
+
Ni
+
+
+
+
+
+
+
+
+
¢
. . .
X
-~
.
+
-7-
+
+
+
+
+
+
X
+
+
+
+
+
+
R
+
+
i-
+
+
+
+
+
+
+
+
-h
+
+
+
+
+
+
+
+
+
+
+
+
R
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-t-
++
X
R
+
+
+
-
+
-i-
+
:+
+
+
X
+
X
+
S
+
+
X
+
X
+
+
+
+
X
X
X
112
+
+
.
t
X
+
R
%
+
R
+
%
+
.
TABLE A2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE RATS: HIGH DOSE
(Continued)
STUDY
CARCASS
YD
Esophagus
Intastine large
Intestine large, cecum
Intestine large, colon
9
8
9
8
9
9
0
0
0
0
0
1
0
1
0
2
0
2
0
3
0
3
0
3
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
2
8
2
9
1
0
1
4
3
7
1
1
4
4
2
5
2
7
1
9
2
9
2
9
1
1
2
1
3
2
2
4
1
5
1
6
1
6
2
6
3
7
2
1
1
2
1
3
1
-i+
+
+
+
+
+
+
-F
+
+
-r
+
-F
F
+
i
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
A
+
+
+
f
+
+
+
t
-F
+
+
+
+
+
tt
A
A
it
~t
+
+
+
+
+
+
+
+
+
+'
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
±
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
..
+
. . +
+ +
+
+
+
+
+
+
+
t
+
+
+
.t
+
i-
.
+
+
+
+
+
t
+
i-,
+
-F . +
+ +
+
Intestine large , rectum
Intestine small
Intestine small, duodenum
Leukemia mononuclear
Intestine small, ileum
Leukemia mononuclear
+
+
Intestine small, jejunum
.
Liver
Hspatocallular adenoma
Hsstiocytic sarcoma
Leukemia mononuclear
NeoplasCic nodule
+
+
M
+
+
-i-
+
+
+.
+
+
+
Pancreas
Leukemia monoauclear
Mesothelioma malignant
Salivary glands
Leukemia mononuclear
Stomach
Stomach, £orestomach
Mesothelioma malignant
Stomach, glandular
Leukemia mononuclear
Tooth
Pulp, leukemia mononuclear
.
~-
+
A
+
+
+
+
+
+
+
+
+
+
t
+
i-
+
A
t
+
+
+
i-
+
+
+
+
+
+
+
+
X
X
X
R
+
+ -+
+
+ ` .
X
+
+
+
+
+
R
+.
.. .
+
+ . -1-
+
t
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
i+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
t
R
+
+
+
+
+
+
+
.
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
f
+
^
+
+
+
+
+
i-
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
X
+
X
+
+
.
+
+
i+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Adrenal gland, medulla
Leukemia mononuclear
Pheochromocytoma malignant
Pheochromocytamabenign
Bilateral, pheochromocytoma benign
+
+
+
Parathyroid. gland
Leukemia mononuclear
Pituitary gland
Leukemia mononuclear
Pars distalis, adenoma
Thyroid gland
Leukemia mononuclear
C-cell, adenoma
Gcell, carcinoma
Follicular cell, adenoma
+
+
X
+
+
+
+,
+
+
+
+
+
+
.
t
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+ . +
+ +
+
+
R
+
x
+
+
+
+
+
~4~
+
+
+
+
-F
+
+
+
+
+
+
+
+
+
.+
+
+
+
'+
+
+
+
+
+
+
+
X
+
X
A
%
%
X
%
+
+
+
+
+
+
+
+
+
+
+
+
X
%
-i-
X
+
+
+
+
R
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
X
+
+
+
+
+
X
t-
X
+
i-
+
.X
.
+
+
+
K
+
+
R
+
R
+
+
Adrenal gland
Adrenal gland, cortex
IC
+
+
+
X
X
X
t
+
+
+
+
+
+
+
+
+
+
+
+
f
X
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
A
+
+
+
A
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-F
+
r
7C
i-
+
i-
X
+
+
t-
.
+
+
+
+
+
x
+
Islets, pancreatic
+
+
+
+
Leukemia mononuclear
i-
+
7C
Heart
Leukemia mononuclear
Schwannoma, NOS
-I-
+
.
7C
Mesentery
Leukemia mononuclear
BHesothe3ioma malignant
+
+
1-
+
+
+
+
t
+
X
+
+
+
+
+
+
t
-+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
+
x
+
+
+
+
+
+
+
t
+
+
+
+
+
+
X
+
.
.
None
Coagulating gland
Leukemia mononuclear
Epididymis
Leukemia mononuclear
Mesothelioma malignant
Preputial gland
Adenoma
Carcinoma
Leukemia mononuclear
Prostate
Leukemia mononuclear
Seminalvesicle
Leukemia mononuclear
Testes
Leukemia mononuclear
Bilateral, interstitial cell, adenoma
Interstitial call, adenoma
Tunic, mesothelioma malignant
+
.
+
+
+
i-
+
+
+
.
+
+
+
+
+
+
t
+
+
+
+
+.
+
+
+
+
+
+
+
+
+
X
+
+
-h
.
+
t
+
x
+
i-
+
X
+
R
+
+
+
+
+
+
R+
+
+
+
+
+
T
t
+
+
X
+ . +
+
t
+
S
t
+
+
+
+
X
+
+
t
+ ._
+
.
+-
r
+
+
+
+
+
.
+
+
+
+
+
+
+
r
+
+
+
+_ +
+
+
+
X
X'
X
R
X
R
X
X
$
+
+
R
+
.
X
+
+
X
+
+
%
+
+
X
+
+
X
+
+
7t
113
+
+
R
+
+
%
+
+
R-
+
+
+
+
IC
+
+
R
+
+
~
R
X
X
'
xyaroquimone, NTP °rR 366
TABLE A2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE RATS : HIGH DOSE
(Continued)
WEEKS
STUDY
N
CARCASS
ID
ALIMENTARY SYSTEM
Esophagus
Intestine large
Intestine large, cecum
Intestine large, colon
Intestine large, rectum .
Intestine small
Intestine small, duodenum
Leukemia mononuclear
Intestine small, ileum
Leukemia mononuclear
Intestine small, jejunum
Liver
Hepatoce}lularadenoma
Histiocytic sarcoma
Leukemia mononuclear
PTeopIastic nodule
.
Mesentery
Leukemia mononuclear
Schwannoma, NOS
ENDOCRINE SYSTEM
Adrenal gland
1
0
5
1
0
5
1
0
S
1
0
5
3
3
2
3
3
3
3
3
4
3
8
1
3
9
1
+
+
+
+
+
+
+
X
+
+ +
+ +
+ +
+ +
+ . +
+ +
+ i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
i.
+
+
+
+
R
X
X
X
.
`
+
-f-
+
+
+
X
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
-r
+
+
+
A
+
X
+
+
+
+
+
+
+
+
X
X
+
+
-F
7C
+
X
X
+
Parathyroid gland
Leukemia mononuclear
Pituitary gland
Leukemia mononuclear
Pars distalis, adenoma
Thyroid gland
Leukemia mononuclear
Gcall, adenoma
Gcoll, carcinoma
Follicular cell, adenoma
+
+
N1.
+
+
+
X
+
+
+
+
X
+
-F
+
+
55
54
50
53
52
55
55 `
1
49
1
48
55
1
1
30
1
.
°
.
.
.
.
-
.
.
.
.
+
X
A
.
" .
%
+
X
Islets, pancreatic
-
X
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochromocytoma malignant
Pheochromocytoma benign
Bilateral, pheochromocytoma benign
Adrenal gland, cortex
TOTAL :
TISSUES
TUMORS
+
Leukemia mononuclear
Mesothelioma malignant
Pancreas
Leukemia mononuclear
MesotLelioma malignant
Salivary glands
Leukemia mononuclear
Stomach
Stomach, forestomach
Mesothelioma malignant
Stomach, glandular
Leukemia mononuclear
Tooth
Pulp, leukemia mononuclear
CARDIOVASCULAR SYSTEM
Heart
1
0
5
9
fi ,
1
54
5
1
55
5
55
55
` 1
55
I
10
8
.
.
.
.
-
55
20
55
+
.
+
54
.
X
X
+
+
+
+
+
+
X
+
+
+
+
.
+
.
-
X
.
_
-
19
55 ;
18
3
13
6
54
54
1
54
8
5
55
3
3
3
1
GENERAL-BODY
None
GENITAL SYSTEM
Coagulating gland
Leukemia mononuclear
. Epididymis
Leukemia mononuclear
Mesotbelioma malignant
Preputial gland
Adonoma
Carcinoma
Leukemia mononuclear
Prostate
Leukemia monoaucIear
Seminal vesicle
Leukemia mononuclear
Testes
Leukemia mononuclear
Bilateral, interstitial cell, adenoma
Interstitial cell, adenoma
Tunic, mesothelioma malignant
+
+
+
+
+
+
i
+
+
+
X
+
i-
+
¢
+
+
+
+
-h
+
+
+
+
A:
7C
X
X
X
+
R
+
X
%
Hydroquinone, NTI' B'IZ 366
2
1
-
55
3
1
54
7
3
.
114
7
55
5
55
6
55
6
43
6
1
.
TABLE A2, INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE RATS : HIGH DOSE
(Continued)
o 0 0 0 o u o 0 0 08 08 08 o8 a8 o9
wE~xs r~
STUDY
FD~C~S
+
Bone marrow
Leukemia mononuclear
Lymph node
Inguinal, leukemia mononuclear
Lumbar, Ieukernia mo¢onnclear
Mediastinal, leukemia mononuclear
mononuclear
Pancreatic, leukemia
Renal, leukemia mononuclear
Lymph node, mandibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
Spleen
Leukemia mononuclear
Thymus
Leukemia mononuclear
.
+
+
+
i
+
+
+
+
-F
+
9
3
6
4
2
3
+
X
i-
i-
-F
+
X
t
+
1C
f
+
+
.
+
x
+
R
+
X
-ix
8
8
1
8
5
0
5
9
4
0
4
5
4
5
3
8
4
9
4
9
4
5 . 3
0
3
8
4
+
R
+
+
X
+
+
X.
+
+
%
t
t
X
+
X
+
X
+
+
%
+
+
%
+
iX
+
i-
A
+
X
+
+
+
X
+
R
+
X
M
+
+
X
+
X
Pdd
+
X
+
R
+
X
t
7C
t
+
+
+
+
+
+
+
M
+
+
t
t
+
+
.
X
+
X
+
X
+
%
+
-1
I-
+
+
i-
t
+
%
t
+
+
R
+
X
%
A
X
+
R
+
X
+
X
+
R
+
X
+
X
+
%
+
R
f
+
x
+
t
R.
+
R
+
X
+
+
+
k
t
-t-
+
+
i-
+
+
+
X
+
+
X
+
+
R
+
9
6
9
6
9
7
7
2
8
3
7
3
8
2
+
X
-i-
t
+
X
+
+
+
+
.
+
+
+
+
¢
+
+
+
+
+
+
+
+
X
t
+
R
+
%
+
R
+
R
+
+
X
+
X
+
R
+
+
+
+
.
+
X
+
X
+
X
+
IC
t
+
t
lL
t
%
+
R
+
+
+
+
+
+
+
i+
+
+
+
+
+
+
+
+
+
t
+
+
+
-F
+
+
+
+
+
t
+
+
+
+
t
+
t
t
t
+
+
+
t
+
t
t
t
t
i-
+
+
+
+
+
+
.
+
+
.
Rib, ostoosarcoma
Skeletal muscle
Leukemia mononuclear
OsCeosarcoma, extension, metastatic,
bone
- Leukemia mono¢uclear
Meainges, leukemia mononuclear
Spinal cord
Meninges,leukomia mononuclear
+
x
-
t
.
Larynx
Lung
+
Fiistiocytic sarcoma
Leukemia mononuclear
Osteosarcoma, metastatic, bone
Pheochromocytoma malignant,
metastatic, adrenal gland
i-
Nose
Leukemia mononuclear
+
Trachea
t
-i-
+
,
+
-i-
+
+
+
-t-
+
X
+
X
X
+
x
t
+
X
.
7°
+
+
+
+
+
+
X
X
X
X
X
R
+
+
+
it
i-
+
X
+
X
.
+
+
x
i-
+
X
¢
i-
x
+
+
+
+
X
+
+
+
+
t
+
-4-
+
%
%
+
+
.
+
+
+
+
+
+
+
+
-9-
+
+
+
+
+
%
X
+
+
X
X
X
X
+
+
+
+
X
115
+
+
t-
X
+
+
X
+
+
X
+
+
+
+
+
x
+
.
+
+
t
+
+
+
+
+
+
X
X
R
t
t
+
+
"
.
+
+
+
+
+
+
+
+
t
-F
+
+
+
+
+
+
+
X
+
+
X
t
+
.
+
R
+
A
+
X
+
+
+
+
+
R
R
34
X
+
+
+
+
R
t
+
+
x
+
+
+
+
+
,
+
+
_
+
X
+
+
+
+
Eye
Harderian gland
Zymbal gland
Carcinoma
Kidney
Histiocytic sarcoma
Leukemia mononuclear
Renal tubule, adenoma
Urinary bladder
Leukemia mononuclear
1
5
7
+
+
8
3
7
+
+
4
4
6
9
1
+
+
9
6
8
6
+
+
9
6
8
3
f
X
.
i-
9
6
8
1
t
i
9
3
8
0
+
+
9
3
0 0 0
9
2
8
0
+
+
o a o 0 0 0
7
5
x
Hone
Brain
7
2
-7-7-6
5
4
5
Blood
Leukemia mononuclear
Mammary gland
Skin
Basal call adenoma
Keratoacanthoma
Subcutaneous tissue, leukemia
mououuclear
6
8
4
6
i-
+
X
X
+
+
+
+
+
K
.
+
+
X
R
+
+
,
Hycirocgtainone, NTP TFZ 386
WEEK
STUDY
1
0
CARCASS
ID
8
8
9
0
4
1
1
0
2
8
2
8
1
0
1
4
3
7
1
1
4
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lyrnph node
Inguinal, leukemia mononuclear
Lumbar, leukemia mononuclear
Mediastinal,leukecnia mononuclear
Fancreatic, leukemia mononuclear
Renal, leukemia mononuclear
Lymph node, mandibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
Spleen
Leukemia mononuclear
Thymus
Leukemia mononuclear
X
+
A
+
t
+
+
1
5
2
7
1
9
2
9
2
9
1
1
1
0
1
0
1
0
1
0
1
0
1
0
1
0
5
1
6
1
6
2
6
3
7
2
1
1
2
1
3
1
i-
-F
-h
-F
+
+
+
+
+
+
+
+
+
i-
+
+
+
1
1
X
+
B
+
+
+
+
.
+
+
+
t
X
+
+
+
+
+
+
M
+
+
+
x
+
%
+
X
+
M +
M .+
+
+
+
+
+
.
.
-9-
+
+
+
+
+
X
-I-
+
+
` +
+
+
+
+
+
t
+
+
i-
.
2
2
+
+
+
+
-I-
i
4
1
-F
X
+
.+
+
+
-F
+
t
R
+
+
R
+
-t
X
+
Y
+
R
+
X
+
+
+
+
1
3
1
2
'r
M
+
%
+
+
5
5
5
5
5
5
;
+
j
+
+
~-
+
-F -
+. +
+
+
+
+
t
+
+
+
+
+
M
+
+
X
+
+
.
+
+
+
X
+
+
F
.
A
+
+
.
,
+
+
x
+
x
+
X
+
+
+
p'
t
t
.
+
R
+
%
t
X
M
+
-h
+
+
+
t
+
+
i-
+
+
+
+
+
-F
i-
+
+
.
+
+
+
.
+
+
+
+
t
+
+
+
+
-h
%
-F
k
R
+
+
X
+
+
f
+
+
R
M
+
+
+
.
i-
+
i-
+
+
+
+
.
-F
i' -
+
.
+
+
+
X
+
+
+
+
+
+
+
+
~
t
'
1
.
.
i-
+
+
+
+
+
+
+
+
+
+
x
+
+
R
+
X
+
+
+
+
+
+
--E
-F
.
t
-F
.
.
+
+
+
+
R
+
+
+
+
+
i-
+
+
+
+
t
+
+
+
+
.
+
+
+
i-
.
.
R
+
+
+
+
+
+
+
.
-h
+
+
+
t
-F
+
-h
+
+
+
+
+
+
X
+
+
+
+
R
+
t
+
116
+
+
+f
+
X
+
+
+
M
'
.
+
.
+.
A.
R ++ ++ + + ++ ++ . +
+
5
. +
R
i'
-
Eye
Harderian gland
Zymbal gland
Carcinoma
Hydroquinone~ IVTP .TR 366
+
+
-
F3istiocytic sarcoma
Leukemia mononuclear
Renal tubule,adenoma
Urinary bladder
Leukemia mononuclear
+
+
Rib, ostmosareoma
Skeletal muscle
Leukemia mononuclear
Osteosarcoma, extension, metastatic,
bone
Kidney
1
+++ + -d ~fr + ++t + + + . X
+
+
X
+
Bone
~F~~PSYEATbYF
Larynx
Lung
Fiistiocytic sarcoma
Leukemia mononuclear
Osteosarcoma, metastatic, bone
Phepchromocytoma malignant,
metastatic, adrenal gland
Nose
Leukemia mononuclear
Trachea
1
X
Mammary gland
Skin
Basal cell adenoma
Fieratoacanthoma
Subcutaneous tissue, leukemia
mononuclear
Leukemia mononuclear
Meninges, leukemia mononuclear
Spinal cord
Meninges, leukemia mononuclear
4
2
+
-F
Blood
NERVOU
Brain
1
0 0 1 1 1 1 1 1
9 9 9 0 0 0 0 02 02 03 03 03 05 05 05 05 05 05
N
+
+
+
+
+
+
+
+
R
X
+
+
+
.
+.
+
+
+
.
+
R.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
R
+
R
+
R
+
.
+
._
~L,~
.~ . .
...
.,
~ .
.
~
.
~
~
..
~~
.
.
.
. .
~~
~
,
~ . ~
..
.~
..
~
~
.
..
~
.
~
~
.
.
~
.
.~
.
~ .
~
~
.
.
TABLE A2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE RATS: HIGH DOSE
(Continued)
w~~
rr
STUDY ~
i i i x i '
a o 0 0 0
s
s
s
s
s
CARCASSID
3
3
2
3
3
3
9
3
3 , 8
4
1
3
9
1
+
X
+
X
+
+
X
+
Blood
Leukemia mononnclear
.
Bone marrow
Leukemia mononuclear
Lymph node
inguinal, leukemia mononuclear
Lumbar, leukemia mononuclear
Niediastinal, leukemia mononuclear
Pancreatic, Isukemia mono nuclear
Renal, leukemia mononuclear
Lymph node, mandibular
Leukemia mononuclear
Lymph nods, mesenteric
Leukemia mononuclear
Spleen .
Leukemia mononuclear
Thymus
Leukemia mononuclear
1
.
.
.
Rib, osteosarcoma
Skeletal muscle
Leukemia mononnclear
-p'
+
+
+
+,
+
+
i
+
+
+
+
29
21
55
18
.
X
R
+
X
+
X
+
X
+
X
+
+
Mammary gland
Skin
Basal cell adenoma
Kerataacanthoma
Subcutaneous tissue,leukemia
mononuclear
Bone
TOTAL:
T ISSUES
TUMORS
+
R
+
X
M
+
X
+
X
M
+
+
+
%
+
i-
+
+
+
+
+
+
+
+
i-
-
53
54
x
2
+
55
2
x
_
+
+
+
+
-
Osteosarcoma, extension, metastatic,
Brain
Leukemia mononuclear
Meninges, leukemia mononuclear
card
spinal
Meninges,leukemia mononuclear
'Larynx
Lungg
Histiocyiic sarcoma
Leukemia mononuclear
Osteosarcoma, metastatic, bone
Pheochromooytoma malignant,
metastaCic, adrenal gland
Nose
-Leukemia mononuclear
Trachea
+
+
X
+
X
+
%
~-
+
+
X
X
X
+
X
+
+
7C
+
+
+
+
+
¢
+
+
+
+
+
+
i
1
bone
3
54
16
54
20
55
31
46
10
55
1
55
.
26
55
12
55
fiEIi3-
4
Harderian gland
Zymbal gland
Carcinoma
URINARY SYST
Kidney
Histiocytic sarcoma
Leukemia mononuclear
Renal tubule, adenoma
Urinary bladder
Leukemia mononuctear
+
+
X
X
+
+
+
+ . +
51
25
+
t
Ss
+
,117
Hydroquinone, NTlP 'I'R. 366
.
.
.
.
.
.
Adrenal Medulla: I'heocht°amocytoms .
Overall Rates (s)
.Adjusted Rates (b)
Terminal Rates (c)
Day off First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Coc3iran-Armitage Trend Test (d)
Fisher Exact Test (d)
Vehicle Control
25 mg/kg
50 mg/kg
13/55 (24%)
39_4%
8/27(30%)
616
P=0 .022
P=0 .086
P=0 .128
17148(353'o)
652%
6/12 (50%)
57&
P= 0 .021
P = 0 .050
19/55(35%)
64 .7%
9/18(50%)
598
P = 0 .024
P = 0 .088
P=0 .137
F'=0 .147
2/48(4%)
12 .3%
1/12 (8%)
718
P=0.290
P=d .306
3/55(5%)
14 .0%
2/18(11%)
676
P=0 .191
P=0 .241
P = 0 .449
P=0 .309
Adrenal Medulla : Malignant Pheochromocytosaia
1/56(2%)
Overall Rates (a)
3 .7%
Adjusted Rates (b)
1/21(4%)
Terminal Rates (c)
731
Day of First Observation
P=a .131
Life Table Tests (d)
P=0 .Ifi3
Logistic Regression Tests (d)
P=022'7
Cachran-Armitage Trend Test (d)
Fisher Exact Test (d)
Adrenal Medulla: Pheochromocytoma or Malignant Pheociaromocytoma
°
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
Preputial Gland : Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
F'reputiafl Gland : Carcinoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day ofFirst Observation
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
Preputfal Gland: Adenoma or Carcinoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
I-iydroquinone, NTP TR 366
14/55(25%)
42 .5%
9/27(33%)
616
P=0 .012
P = O .Ob:i
P=0 .096
11/53(21%)
38.5%
10127 (37%)
616
19/48(40%)
72 .3%
7/12(58%)
576
P=0 .409
P=0 .024
21/55(38%)
69 .7%
10/18(56%)
598
P=0 .014
P = 0 .057
P = 0 .093
P=0.110
(e) 8/34 (24%)
7/54 (13%)
26 .5%
3/18(17%)
606
P = 0 .485N
P=0 .207N
1/53(2%)
3 .7%
1/27(4%)
731
(e) fl134 (3%)
3/54(6%)
9 .2%
1/18(6%)
601
E' = 0246
P=0 .306
P=0 .316
11/53(21%)
38 .5%
10/27(37%)
616
(e) 9/34 (26°fo)
10/54119%!
34 .1%
4/18(22%)
501
P=0 .402
P=0 .524N
P = 0 .481 N
118
f TABLE As. ' ANALYSIS OF PRIMARY TUMORS IN MALE RATS IN THE Two-YEAR GAvAGE STUDY OF
HYDRoQUINoxE (Continued)
Vehicle Control
25 mg/kg
50 mg/kg
0/65 (0%)
0 .0~'0
0/27.(0%)
4/56(7%)
15 .0%
2/18(I1%)
392
P=0 .042
F=0 .069
8/65 (15%)
35 .0%
51d8(2890)
'
598
P=0 .001
P=0 .003
P=0 .059
E'=0 .003
3/55(5%)
10.2%
2/27(7%)
710
P=0 .585N
E'=0 .b48IeI .
P=0 .407N
2/55(4%)
11 .1%
2/18(11%)
734
P=0 .673N
P=0 .626PT
2/55 (4%)
10 .1%
1118 (6%)
728
P=0.670N
P=0.624N
P=0 .500IV
I'=0.500N
Mammary Gland: Fdbe°oaelenoma
Overall Rates (a)
Adjusted Rates (b) .
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
3/55(5%)
11 .1°lo
3/27(11%)
731 .
F=0 .072N
P=0 .m72N
&'=0 .037IV
0/55 (0%)
O .Q°lo
0/18(0%)
0/55(0%)
0 .0%
0/48(0%)
d'=0 .1991iT
P=0 .1991Y
.199N
P---0
P=0 .199N
P=0.122N
P=0 .122N
Mammary Gland : Adenoma or F'ibroadenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
4/65 (7%)
14 .83'o
4/27 (15%)
731
P=0.036Id
P=0.036201
P=0.015N
0/55 (0%)
d .09'o
0/18(09'0)
0/55(0%)
0 .0~'0
0/18 (0%)
P=0 .122N
P=0 .122N
P=0.122N
P=0.122N
P=0 .059N
P=0 .059N
5/55(9%)
18 .59"0
5/27(19%)
731
P=O .Ofl8N
P=0 .018Pd
P=0 .006I+d
0/55(0%)
0 .0%
(3/18(05'a)
0/56(0%)
0 .03'0
d/18(O%)
P =0 :075N
P =0 .076N
P=0 .075N
P=0 .075N
P=0 .028rd
P=0 .029N
13/54 (24%)
35 .5%
6/27(22%)
459
P=0.125IV
F=Q.031N
P=0 .026N
9/54 (17%)
35 .2°fo
3/17(18%)
466
P=0 .b38N
P=0 .3031V
.5/54(9%)
18 .7%
1/18(6%)
598
P=0 .1271V
P=0 .038N
P=423?N
P=0 .034N
Kidney : Renal Tubule Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c),
Day of First Observation
'
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
Liver : Flepatmcell'atar Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Teat (d)
Fisher Exact Test (d)
P<0 .001
P=0 .003
P=0 .003
.
Mammary Gland: Adenoma, F1bC02d8IY0(Y&ay or AdeH$oCBCCII'90E$i(d
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
Pituitary Qalanci/Pars Distalis : Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
119
Hydrocguinone ;lVTF TR, 366
TABLE A3. ANALYSIS OF PRIMARY TUMORS IN MALE RATS IN THE TWO-YEAR GAVAGE STUDY OF
HYDRC9QiJI1VONE (Continued)
25 mg/kg
50 mg/kg
13/54(24%)
35 .5°%
6/27(22%)
459
F=0 .130N
P=d .033N
P=Q.028N
10/54 (19%)
37 .0%
3/17(18%)
466
P=0 .548
P=0.392PI
5/54(9%)
18 .7%
1/IS (6'Xa).
598
F=0 .127N
P=0 .03SN
P=0 .319N
P=0 .034I+T
46/64 (85%)
97 .8%
26/27(96%)
483
P=0.025
I'=0.422
P=b .315
49/54(91%)
100 .0%
171Y7 (100%)
392
F'=0 .015
P=0 .06i
49/65(89%)
100 .0%
18/18 (100%)
522
P=fl .028
P=0 .489
F'=0 .276
P=0 .374
(e) 2l3$ (b°dr)
3/55(5%)
10 .6%
1/18(6%)
581
Vehicle Control
Pituitary Gl3QddIFH$[°S D68tal48 : Adenowa or Carcinoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day ofFirst Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armftage Trend Test (d)
Fisher Exact Test (d)
Testis: Interstitial Cell Adenoma
Overall .Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day ofFirst Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armatage Trend Test (d)
Fisher Exact Test (d)
Thyroid Gland: c-Cell Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day ofFirst Observation
Life Table Test (d)
5/56(9%)
16 .9%
4/27 (15%)
637
~
P=0.51ON
Logistic Regression Test (d)
Fisher Exact Test (d)
Thyroid Gland: C-Celt Carcinoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
P=0 .377N
P=0 .358N
2/55(4%)
6 .3%
1/27(4%)
676
Thyroid Glands C-Cell Adenoma or Carcinoma
Overall Rates (a)
7/55(13%)
Adjusted Rates (b)
22.7%
Terminal Rates (c)
5/27(19%)
Day of First Observation
637
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
Thyroid Gland : Follicular Cell Adenoma or Adeasocarc6aemma
Overall Rates (a)
3/55(5%)
Adjusted Rates (b)
40.4%
Terminal Rates (c)
2/27 (7%)
Day of First Observation
715
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
HydroquYnone, NTP TIZ 366
120
(e) 2/38 (5%)
3/55 (5%)
14 .4%
2/18(11%)
'T00
P=0 .356
E'=0 .434
P=0 .500
(e) 4138 (11%)
6/56 (11%)
24 .096
3/18(17%)
581
F'=0.515 '
P=0 .55ON
P=0 .500N
(e) 0138 (0%)
1/55(2%)
3 .896
0/18(0%)
676
P=0 .4351V
P=0 .3S3N
P=0.309N
"
ABLE A3 . ANALYSIS OF PRIMARY TUMORS IN MALE RATS IN
I3YI2ItOQYTEPTOPJE (Continued)
mb$] Gland: Carcinoma
Overall Rates (a)
Adjusted Rates (b)
' Terminal Rates (C)
"
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
mbal Gland: Adenoma or C1YCIIiOm$
overall Rates 4aD
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Rcmitage Trend Test (d)
Fisher Exact Test (d)
Vehicle Control
25 mg/kg
50 mg/kg
1155(2%)
2 .6%
3/55(5%)
12 .2%
1/55(2%)
654
P=0 .543
P=0 .610
P=0 .610
653
P=Q232
P=0.276
P=0 .309
P=0 .7b2N
1/55(2%)
2.6%
0/27(0%)
654
P=0 .505
E'=fl .604b
P=0 .602
4155(7%)
16 .4%
1/18(6%)
653
F'=0 .117
P=(F .149
1/55(2%)
1 .9%
0i18(0%)
473
P=0 .758
I'=0 .736
P=0 .982
E'=0 .752PI
26/65(47%)
6'7 .3%
7I18(39%)
263
P=0 .263
P=0 .488N
31/55(56%)
79 .9%
12/18(67%)
522
P=0.086
P=0.360
P=0 .424N
P=0 .3b1
3/55(5%)
10 .2%
1/18(6%)
392
P=0 .227
P=0 .319
1/55(2%)
5 .6%
1/18(6%)
731
P=0 .669
P=0 .669
P=0 .3t}9
P=0 .752N
0/27(0%)
ema$mpoietec System : Mononuclear Leukemia
28/55(51%)
Overall Rates (a)
Adjusted Rates (b)
71 .6%
17/27 (63%)
Terminal Rates (c)
367
Day of First Observation
P=0 .083
Life Table Tests (d)
P=0 .314'
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
P=0 .317
Fisher Exact Test (d)
All Sites: Malignant Mesothelioma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-A.rmitage Trend Test (d)
Fisher Exact Test (d)
E TWO-YEAR GA`'AGE STUDY OF
1/55(2%)
3 .79'o
1/27(4%)
731
P=0 .514
P=0 .610
P=0 .610
1/18(S%)
1.9%
~ 0/18(o%)
473
P=0 .755
F'=0 .736
(a) Number of tumor-bearing animals/number of animals examined at the site
(b) IfapFan-Meier estimated tumor incidences at the end of the study after adjusting for intercarrent mortality
(c) Observed tumor incidence at terminal kill
(d) Beneath the vehicle control incidence are the P values associated with the trend test. Beneath the dosed group incidence are
the P values corresponding 4o paieevise comparisons between that dosed group and the vehicle controls. The life table analysis
regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. The logistic regression test regards these lesions as nonfatal . The Cochraaa-t0emi4,ags and Fisher exact tests compare directly the overall incidence
rates . A negative trend or lower incidence , in a dosed group is indicated by (N).
(e) Incomplete sampling of tissues
121
Hydroquinone, NTP °i'R 366
TABLE A4a. HISTORICAL INCIDENCE OF KIDNEY TUBULAR CELL TUMORS IN MALE F344/N RATS (a)
Incidence of
Adenomas or ?adetxacarcinasmas
in Controls
Study .
Historical Incidence for All Water Gavage Vehicle Controls
.
0/50
0150
0/50
0/50
Todinated glycerol (b)
Malonalclehqde, sodium salt (c)
Chlorpheniramfine maleate (c)
Tetsakis(hydroaymethyl)phosphonaragn chloride (c)
T'etgakis(hydrosqmethy2)phosphoniaun sulfate (c)
Methyl caebamate (d)
0/48
(e)1150
1/298 (0 .3%)
0 .82%
TOTAL
SD (f)
Range tgD
High
Low
i/5o
U/50
Overall Historical Incidence for Untreated Controls
(h) 9/1,928 (0 .5R'o)
TOTAL
1 .17%
SD (f)
Range (g)
3/50
0150
High
Low
(a) Data as of April 29, 4987, for studies of at least 104 weeks
(b) Study performed at EG&G Mason Research Institute
(c) Study performed at Battelle Columbus Laboratories
(d) Study performed at Miceobiologicai Associates
(e) Tubular cell adenocarcinoma
(f) Standard deviation
(g) Range and SD are presented for groups o$' 36 or more animals.
(h) Includes one.adenoma, NOS, six tubular cell adenomas, one tubular cell adereocarcinoma, and one tubular adenocarcinoma
Hyclroquinone, NTP `r1Z, 366
122
FABLE A4b.
HISTORICAL INCIDENCE OF ADRENAL GLAND
RATS (a)
Pheochromocytoma
Study
MEDuLLARY TUMORS IN MALE F344/N
Incidence in Controls
Malignant
Pherachromacytoma
Pheochromocytoma
or IN[adignazat
Pheochromocytoma
fiistorecal Incidence for All Water Gaeage ''Vehicle Controls
:odinated glycerol (b)
VYaIonaldehyde, sodium salt (c)
'hlorpheeadramine maleate (c)
Cetrakis(hgdroxymethyl)phosphoraiuBn chloride (c)
Petrakis(hydrosymethyl)ghosphoniuen sulfate (c)
4fethyl eaebamate (d) ,
TOTAL
SD (e)
iange Cfl
High
Low
23/50
5150
2I/49
19/64
22/5Q
23150
113/299 (37 .89b)
43 .94%
23160
5l50
5150
. 0/50 .
0/49
Q/50
1/50
4/50
28150
5150
21/49
19/b0
23150
25/50
10/299 (3.3%)
4 .509'0
5/50
0/60
121/299 (40 .5%)
16 .14%
28/50
5/50
)verall Historical Incidence for Untreated Controls
TOTAL
SD (e)
tangs (t)
High
Low
45911,915 (24 .0%)
13 .30g'o
31149
2/50
37/fl,915 (g .9%)
2.70°lo
6150
0/50
489/1,9P6 (25 .6R'o)
I3 .659'0
32/49
3/50
(a) Data as of'April 29, 1987, for studies of at least 1(D4 weeks
(b) Study performed at EG&G Mason Research Institute
(c) Study performed at Battelle Columbus Laboratories
(d) Study performed at Microbiological Associates
(e) Standard deviation
(f) Range and SD are presented for groups of 35 or more animals .
123
Hydroqaairaoney NTP TR, 366-
TABLE A4e . HISTORICAL INCIDENCE OF ANTERIOR PITUITARY GLAND TUMORS IN MALE F3441N
RATS (a)
Adenoma
Study
Incidence in Controls
Carcinoma
Adenoma or
Carcinoma
Historical Incidence for All Wader Gavage Vehicle Controls
25/48
20/47
12150
17150
21/50
26/b0
Fodinated glycerol (b)
Malonaldehyde, sodium salt (c)
Chlorpheniramiafe maleate (c)
"letrakis(hydrogyymethyl)phosphonium chloride (c)
Tetrakis(hydrozgmethyl)phosphonium sulfate (c)
Methyl carbasnate (d)
TOTAL
SD (e)
121/295(41 .0%)
fl(3 .829~0
Range (f)
High
LOW
25i48
12/50
1/48
0/47
0/50
4150
0/50
3/50
5/295(l .7%)
2 .34% - 3/50
0/50
26148
20147
12l50
18J50
21150
29J50
.
126f295 (42.7%)
12 .339'0
29/50
12150
Overall Historical Incidence for Untreated Controls
TOTAL
SD W
Range (fl
High
,ow
(g) 417/1,II30 (22 .8%)
10 .75%
24146
2/39
(a) Data as of April 29,1987, for studies of at least 104 weeks
(b) Study performed at EG&G Mason Research Institute
(c) Study performed at Battel9e Columbus Laboratories
(d) Study performed at IMicrobiotogical Associates
(e) Standard deviation
(#) Range and 5D are presented for groups of35 or more animals.
(g) Includes 32 chromophobe adenomas and 1 acidophil adenoma
(h) Includes seven chromophobe carcinomas and one adenocarcinoma, NOS
Hydroquinone, NTPTIt 366
124
(h) 42I1,930 (2 .3%)
2 .85R'o
5145
0/50
(g,h) 459/I,830 (25 .1%)
1d .323'0
25/46
2/39
'
TABLE A5 . SUMMARY OF THE INCIDENCE OF NONNEOPLASTIC LESIONS -IN MALE RATS IN THE
TWO-YEAR C~"AVACs°F'. STUDY OF HYDROQUINONE .
Vehicle Control
Animals initially in study
Animals removed
Animals examined histopathologicaflly
ALIMENTARY SYSTEM
Intestine large, cecum
Ulcer
SVenuie ; thrombus
Intestine large, colon
Mineralization
Muscu2aris, inflammation, chronic
Muscularis, mineralization
Serosa, inflammation, chronic
Intestine large, rectum
Edema
Hemorrhage
Muscularis, mineralization
Intestine small
Capillary, degeneration, hyaline
Intestine small, duodenum
Ilduscularis, inflammation, chronic
Intestine small, ileum
Capillary, degeneration, hyaline
Muscularis, inflammation, chronic
Muscularis, mineralization
Liver
Basophilic focus
Clear cell focus
Concretion
Cytomegaly
Degeneration, cystic
EO$lllOj3j1Yl1CCpCUS
Fatty change
Focal cellular change
Hematocyst
Hematopoietic cell proliferation
Fiepatodiaphragmaticnoduie
Ffyperplasia,Foca1
I-Iyperpiasia, multifocal
Inflammation, chronic
Mixed cell focus
Necrosis, COSg11l8tIVB
Necrosis, coagulative, multifocaI
Arteriole, inflammation, proli4'eratiee
Arteriole, thrombus
Bile duct,dilatation
Bile duct, hyperplasia
Centrilobular, atrophy
Serosa,t`abrosas,focal
Serosa, inflammation, chronic
Sinusoid, dilatationVein, dilatation
Mesentery
Accessory spleen
Fat, inflammation, chronic
Fat, inflammation, granulamatous
Fat, mineralization
Fat, necrosis
Lymphatic, ectasia
65
65 ,
55
Low Dose
65
65
55
(50)
1 (3%)
($2)
1 (3°l0)
1 (3%)
(53)
(52)
(36)
(52)
(35)
(48)
(33)
(55)
11
1
1
2
26
(20%)
(2%)
(2%)
(4%)
(47%)
4 (`I%)
5 (93'0)
2 (4'%)
6 {115'o)
1 (2%a)
18 (33%)
6 (ll%)
7
(S3%)
1
54
5
!
(23'0)
(98%)
(9%)
(29'0)
2 (4%)
(12)
4
1
1
3
1
65
6s
56
(34)
1 (3'%)
fl (3%)
(g5)
(51) .
(33%)
(8
(8%)
(259'0)
(8%)
125
(55)
11 (2fD%)
7 (139'a)
1 (2%)
23 (42%)
`L
4
1
1
3
10
(4ala)
(7'%)
(2~'0)
(2%)
(5~'a)
(18%)
fl (2%)
19 (359'o)
2 (45'0)
4
('l%)
52 (9596)
8 (15%'o)
1
7
1
d16)
3
3
High Dose
(2%)
(g3%)
(2%)
(19%)
{399b}
1 (6%)
(50)
(53)
1 (23°0)
1 (2%)
2 (4%)
(52)
1
(55)
1
(55)
i
(49)
4
L
1
(b5)
6
4
(2%)
(2%)
(23'0)
(23'0)
(29b)
(2R'o)
(Y1%)
(7%)
3
18
1
4
(5%)
(33°lo)
(2'36)
(73'0)
I
9
1
1
19
(29!0)
(1696)
(2%)
(296)
(35%)
7
E
3
2
(133'0)
(250)
(59'0)
(4%)
54 (98%)
10 (Y83'o)
4 (7%)
(9)
2 (22°!0)
Hydroquinone,NTP TR, 366
TABLE A5. SUMMARY OF THE INCIDENCE C9I'+ NONNEH2PI .AS'TIC LESIONS IN MALE RATS IN THE
TWO-YEAR (aAiyAGE STUDY OF HYI)TtOQUIN6DNE (Continued)
Low Dose
Vehicle Control
ALIMENTARY S'Y'STEM (Continued)
Pancreas
Atrophy
I'IypePpISS18ls nodular
.
Inflammation, chronic
Acinus, tayperplasia
Arteriole, inflammation, chronic
Duct, inflammation, chronic
Pharynx
Abscess
Salivary glands
Atrophy, focal
Cytogrlasenic alteration
Hyperplasia
I9uct, hyperplasaa
Duct, inflammation, chronic
Duct, metaplasia,squamous
Stomach,Forestomach
Abscess
Acanthosis
Edema
Hemorrhage
Fiyperkeratosis
Hyperplasia, papillary
Inflammation, chronic
Ulcer
Ulcer, chronic
Epithelium, degeneration, ballooning
Musctalaris, mineralization
Stomach, glandular
Erosion
Inflammation, acute
Inflammation, chronic
Mineralization
Ulcer
Tooth
Pulp, proliferation connective tissue, focal
CARDIOVASCULAR SYSTEM
Heart
Cardiorrayapsthy
Mineralization
Thrombus
Atrium, dilatation
Atrium, thrombus
ENDOCRINE SYSTEM
Adrenal gland, cortex
Accessory adrenal cortical nodule
Angiec4,asis
Cyst
L3egeneration,fatty,focal
Hyperplasia
Necrosis, coagulative
;7acuolizationcytoplasmic
Capsule, hyperplasia
Adrenal gland, medulla .
Atrophy
Fibrosis
Heenatopoietic cell proliferation
Hyperplasia
Hydroquinone, NTP'Pit 366
(36)
6 (1Z%)
I (3%)
(53)
6 (11%)
1 (29'0)
1
1
1
(1 )
I
(54)
(2%)
(2%)
(2%)
(lOQ%)
(37)
,
I t29"o9
15 (28%)
12 (22%)
(5b)
1 63%9
1 (3%)
3 (Sqo)
2 (S%)
(36)
fl (3%)
3 (5°0)
1 (2%)
(4%)
(5%)
(7%)
(2%)
2
2
3
g
1 (2%)
(6%)
(3%)
(8%)
c3%,
(34)
1 (39'0)
1 (3%)
1 (39'a)
(54)
1 (3qn)
(9)
(8)
(38)
28 (74%)
(55)
46 (84%) .
fl (2%)
4 (7%)
(54)
'
fl (3%)
5 (13%)
7 (1s%)
5 (9%)
(55)
1 (2%)
49 (3bqa)
126
(55)
1 (2qo)
6 (9%)£ (11%)
(55)
2 (4%)
2
4
1
Y
(49'0)
(2%)
(2%)
(2%)
(55)
1 (2%a)
5 (9%)
1 (2eYo)
(40)
(55)
47 (8596)
7 (13%)
fl (2%)
4 (7°fo)
(54)
(37)
1 (2%)
1 (23'0)
6 (fll%)
(54)
5 (9'30) : .
1 (2%)
2 (49'0)
2
3
4
1
High Dose
1 (z%)
1
4 (11%)
(2%)
6 (11%)
4 (ii%)
ia c2o%,
(19%)
(3%)
7 -(Y3%)
1 (2%)
(55)
fl
7
1
(48)
1
i
(2%a)
(29a)
'
19 (4096)
22 (40%)
;
ENDOCRINE SYSTEM
Adrenal gland, medulla (Continued)
Mineralization
Islets, pancreatic
HYPegpTasia
Parathyroid gland
Cyst
Hyperplssia
Pituitary gland
Paesdistalis,cyst
Pars distalis, fibrosis
F'ars distalis9, hemorrhage
Pars disY.alis, hyperplasia
Pars distalis, necrosis
Pars intermedia, cyst
Thyroid gland
Ultimobranchial cyst
C-cell, tsyperpIasia
Follicle, cyst
Follicular cell, hyperplasia
(55)
(54)
3 (63"a)
(54)
13 (24%)
(54)
? (139'o)
1 (2%)
12
1
1
(55)
2
4
(229'0)
(2%)
(29'0)
(44'o)
(7%)
1 (2%)
(48)
1 (2%)
(36)
2 (6%)
(36)
6 (17'90)
(54)
8 (15%)
1 (2%)
14 (B6R'o)
1 (2g'o)
(3fi)
5 (13%)
4 (3~'0)
(55)
(54)
(b4)
1 (2%)
19 (3Ps3b)
(54)
7 (13%)
-
11 (20%)
(55) 1 (29'a)
7 (I3%)
GENERAL BODY SYSTEM
None
GENITAL SYSTEM
Coagulating gland
Inflammation, chronic
Inflammation, suppuratnve
Epididymis
Degeneration, mucoid
Inflammation, chronic
F'reputisI gland
Abscess
Cyst
Hyperplasia
Inflammation, chronic
Inflammation, suppttrative
Necrosis, coagailative
Pigmentation, hemosiderirt
Prostate
Abscess
Hemorrhage
,
,
',
,
I
'
Hyperplasia
F$ypeeplasia,fooal
Inflammation, chronic
Inflammation, supipuraCive
Seminal vesicle
Inflammation, chronic
Mineralization
Testes
Atrophy
Cyst
Bilateral, interstitial cell, hyperplasia
Interstitial cell,hyperplasia
Seanireiferous tubule, degeneration, cystic
(1)
(53)
1
1
(53)
1
5
2
12
5
(2%)
(2%)
(29'o)
(9%)
(4%)
(239b)
(99'0)
(53)
(2)
2 (140~'0)
(3?)
(34)
1
2
L
13
2
(3%)
(6%)
(3%)
(38%)
(63"o)
(4f)
1 (2%)
3 (6%)
7 (139'0)
9 (17%)
(53)
1 (2%)
(54)
39 (?2°fo)
1! (20~°0)
127
1 (2%)
4
1
1
- 8
(3f)
(54)
31
1
1
7
(10%)
(2%)
(2°Bo)
(20%)
(57g'a)
(2%a)
(23b)
(139'a) .
1 (50%)
(55)
4 (79'0)
(54)
1
7
1
13
P
1
(2%)
(139'0)
(2%)
(24%)
(2%)
(2%)
(55)
1 (23°0)
4 (7~'0)
5 (S3'o)
13 (24Q/o)
(b5)
1 (2%)
(5b)
35 (64%)
1 (2g'o)
7 (I33'o)
1 (2%)
Hydrocquinonem N"PP TR 366
IN MALE RATS %N THE
TABLE A5 . SUMMARY OF THE INCIDENCE OF NOP7NEmPfpAS'I'IC LESIONS
TWO-YEAR GAV.AGrE STUDY OF HI'lJii.OQLRNONE (Continued)
Vehicle Control
HEyJIATOg'63IETIC SYSTEM
Blood
Anemia
Hypersegmentatioas
Left shift
Neutraphilia
Thrombocytopenia
Bone marrow
i (5°!o)2 (9%)
fl
q
1 43%)
2 t5%>
I (2%)
Iliac, hyperplasia, plasma cell
1 ("G%)
Iliac, sinus, BC9:$Sla
Inguinal, hyperplasia, lymphoid
Ixeguinal, hygerplasia, plasma cell
Inguinsl, sinus, ectasia
Lumbar, hyperplasia, macrophage
Lumbar, hyperpBasis, plasma cell
Lumbar, pigmentation, hemosidera`n
Lumbar, sinus, ectasia
Mediastflnaln hyperplasia, macrophage
Mediastinal, hypeeplasis, plasma cell
NFediastinal, pigmentation, hemosideirin
Merliastinal, sinus, ectasia
Pancreatic, hyperplasia, macrophage
Pancreatic, sinus, ectasia
Renal, pigmentation, hemosiderin
Renal, sinus, eetasia
Lymph node, mandibtilar
Congestion
Fiyperplasia, lymphoid
Hgperplasia, plasma cell
Sinus, ectasia
Lymph node, mesenteric
Congestion
Depletion lymphoid
I--Yygerplasfa, macrophage
Hyperplasia, plasma cell
Pigmentation, hemosiderin Sinus, ecfasia
Spleen
Fibrosis
Hernatapoietic cell proliferation
Hemorrhage
I-Iyperplasia, macrophage
Capsule, infarct
1 (2°Jo)
1 (29b)
2 (4%)
1 (2%a)
1 (2%)
2 (4°l0)
1 (2%)
(52)
1 (2%a)
2 (4%)
7 (13%)
(53)
1 (29'0)
3 (6%)
1 (2%)
9 (17%)
(b5)
3 (5%)
1 t2%7
1 (2%)
Capsul e, infl ammation, ch ronic
Red pulp, depletion
Congestion
Cyst
Inflammation
Epithelial cell, hyperplasia
Hydroquinone, NTP TR 366
.
3 (8%)
(41)
fl (2%)
1 (A)
.
y
Corte
x, ~~l11aS41n81y atroph
Thymus
3 (123'0)
2 (8%)
(37)
.
Depletion
Myeloftbrosis
]Erythroid cell, hyperplasia
Myeloid cell, hyperplasia
Lymph node
Bronchial, pigmentation, hemosiderin
Bronchial, sinus, ec tasia
;
(25)
2 t89'o9
1 (4%)
(22)
.
Low Dose
(46)
I (2%)
i
1
1
2
1
(2~%'o)
(2'%)
(2%)
(5gb)
(250)
(2%)
2 (5%)
1 (2%)
1 (2%)
129
(29)
1 (3%)
t55)
3 (S°rb)
2,(4%)
3 (5%)
(55)
1
1
1
1
2
1
(2%)
(2%)
(2%)
(2°k)
(4%)
(2%)
1 (2%a)
1
1
1
3
(2g"o)
(2%)
(2~7'0)
(5%)
1 (29'0)
1 (2%)
(38)
(54)
1 (3%)
4 (dI°lo)
3 (89`0)
(38)
3 (6%)
4 (7%)
(54)
2 (5%)
3 (89'a)
5 (18~'0)
(52)
5 (lO%)
5 (l0%)
1 (2a/o)
(2%)
f357
fl (2%)
High Dose
Y (3%)
1 (3%)
1 (2%)
1 (2%)
1 (29'0)
3 (6%)
(55)
8 (15'Yo)
3 (5°Jo)
1 (2%)
2 (2g'o)
(46)
1 (2%a)
2 (49'0)
LESIONS
MALE RATS IN THE
TABLE A5 : SUMMARY OF THE INCIDENCE OF NODINEO&'LAS'TTC
TWO-YEAR GA't''AGE STUDY OF H'YY3ROQT3iPdONE (Continued)
Vehicle Control
;NT'EGtJMENTAR'Y SYSTEM
(49)
Mammary gland
Cyst
14 (29°k)
Hypsen-plasia
Mineralization
(55)
Skin
Abscess
Cyst epithelial inclusion
Inflammation, chronic
Inflammation, granutoanatous
` Inflammation, suppurative '
inflammation, proliferative
Z
i (25'0)
Ulcer
Right, hizadlimb, subcutaneous tissue,
inflammation, acute
Right, hindlimb, epidermis, abscess, multiple
Right, hindlimb, epidermis, degeneration,
ballooning
Scrotal, inflammation, suppurative
Sebaceous gland, hyperplasia
Subcutaneous tissue, abscess
Subcutaneous tissue, cyst
Subcutaneous tissue, edema
Subcutaneous tissue, hemorrhage
2 (4`Yo)
Subcutaneous tissue, inflammation, chronic
Subcutaneous tissue, inflammation, suppurative
MLTSCLTi.CAxKELETAI. SYSTEM
Bone
Fibrous osteodystrophy
Inflammation, chronic
(29)
(53)
1
10
1
(S4)
1
8 (2E%)
(37)
1 (3%)
4 (73'0)
6 (16%)
1 (3~'0)
Y (39b)
1 (2%)
1 (3%)
2 (4%)
I (3%)
1 (2%)
1 (2%a)
1 C3°!o?
1 (2%a)
{5b)
1 (3%) .
RESPIRATORY SYSTEM
Larynx
Hemorrhage
Inflammation, chronic
Lung
Atelectasis
Congestion
Crystals
Hemorrhage
Fiyperplasia, macrophage
Hyperpfasia, adenoenatous
Inflammation, acute
Inflammation, granuloanaY.ous
Inflammation, suppurative
Mineralization
1 (2%)
1 (I73'o)
1 (26`J6)
(55)
4 (7g'o)
(2'Yo)
I (2%) _
1 (17%)
Mineralization
NERVOUS SYSTEM
Brain
Compression
Cerebellum, embolus tumor
Cerebellum, infarct
Choroid plexus, inflammation, chronic
Ventricle, dilatation
. (2%)
.(19%)
(23'0)
6 . (9%)
3
(37)
(55)
Inflammation, chronic active
Skeletal muscle
Degeneration
High Dose
Low Dose
(55)
3 (5%)
(37)
2 (5%)
1 (3°h)
1 (3%)
1 (3~'0)
(1)
1 (1003'0)
(1 )
1
(55)
(i0o%)
t55?
1 (2%)
(38)
2 (4%)
% (3%'o)
7 (13%)
3 (59'0)
1 (30/0)
2 (5%)
2 (5%)
I (2%)
129
1
3
6
1
(23'0)
(6g'o)
(11%)
(2%)
1 (29'0)
2 (4%)
Hydroqazinone, NTP TR 366
TABLE A5. SUMMARY OF THE INCIDENCE OF NONNEOPI.IsS1'IC LESIONS IN MALE RATS IN THE
TWO-YEAR GAVAGE STUDY OF HYDROQUINONE (Continued)
Vehicle Control .
RESPIRATORY SYSTEM
Lung (Continued)
Necrosis, coagulative
Necrosis, HiquifaCtive
Proliferation connective tissue
Arteriole, thrombus
Arteriole, media, hyperplasia
Bronchiole, foreign body
interstitium, fibrosis
Interstitium, inflammation, chronic
Pleura, inflammation, chronic
Nose
Inflammation, chronic
Infla mmatiort,suppura8ive
MeU2p laaia, sqcaamous
1Vasolacrimal duct, inflammation, chronic
Nasolacrimal duct, inflammation, suppurative
Nasolacsimal duct, rnetaplasia, sqaaasnous
Respiratory epithelium, cyst
Trachea
Exudate
Inflammation, chronic
Glands,cyst
g~
SPECIAL SENSES SYSTEM
Ear
Exixdmt2
Middle ear, inflammation, suppueative
Eye
Hemorrhage
Synechia
Cornea, inflammation, subacute
Cornea, necrosis
Cornea, proliferation
Retina, atrophy
URINARY SYSTEM
Kidney
Cyst
Hemorrhage
Infarct
Inflammation, chronic
Mineralization
Necrosis, coagulative
Nephropath ;y
Pelvis, heanatopoietic cell proliferation
Pelvis, inflammation, suppurative
Renal tubule, hyperplasia
Renal tubule, hyperplmsia, focal
Renal tubule, inflammation, suppurat,ive
Transitional epithelium, hyperplasia, papillary
Urinary bladder
Hypeepiasia, papillary
Inflammation, chronic
Inflammation, chronic active
Submucosa, edema
Hydroquinone,NTP Tlt 366
(55)
i (29'0)
1 (290)
4
4
(55)
8
1
.
27
3
45
(?9b)
(7%)
(169b)
(2~0)
.
(499'0)
(596)
(82%)
(53)
1 (2%)
3 (6%)
4 (S%)
(2)
1 (50%)
(2)
LOW Dose
(38)
(55)
1 (3%)
2 (5%)
(37)
T (F9%)
g
A
22
2
24
1
(37)
(3%)
(57%)
(5%)
(65%)
(3%),
1 (3%)
(3)
4 (33%)
2 (67%)
(55)
2 (4%)
1 (29'a)
27 (49%)
1. (2%)
4 (2%)
53 (96%)
4 (7%)
1 (2°la)
(51)
? (I49'a)
130
1 (2~'0)
1 (2%)
2 (4°k)
fl
1
2
(55)
6
2
(2%)
(2%)
(4°l0)
(fll%)
(4%)
34 (62'Yo)
2 (4%)
47 (85%)
(55)
1 (2%)
2 (43'0)
f2)
1 (50°9o)
1 (33%)
3 (Y00%)
(55)
High Dose
1 (2%)
30 f55%p '
52 (95%)
1 (296)
7
6
(37)
3
f
(13'~'a)
(11%)
{33'0}
(3%)
(4)
1 (25%)
i (2596)
2 (509'0)
(55)
6 (11%)
1 (2%)
27 (49%)
55 (400%)
! (2%)
1 (2%)
1 (2%)
5 (99'o)
(b5)
3 (590)
1 (2R'o)
1 (2%)
.
APPENDIX B
SUMMARY
THE TWO-YEAR
I
I
FA
AGY
131
F
TS I
UI
Hyciroqazinone, NTP TR 366
TABLE B1 . SUMMARY OF THE INCIDENCE OF NEOPLASMS IN FEMALE HATS IN THE TWO-YEAR
GAVE1GE STUDY ()F TTYTDR6'1QUINCDNE
Vehicle Control
Animals initially in study
Animals removed
Animals examined histopathologically
ALIMENTARY SYSTEM
Intestine large, cecum
Leukemia mononuclear
Intestine large, colon
Leukemia mononuclear
Intestine large, rectum
Leukemia mononuclear
Intestine small, duodenum
Leukemia mononuclear
Intestine small, ileum
Leukemia mononuclear
Sarcoma
Intestine small, jejunum
Cystadenocascinoma
Leukemia mononuclear
Sarcoma
Liver
Leukemia mononuclear
Mesentery
Leukemia mononuclear
Pheochromocytoma malignant, extension,
metastatic, adrenal gland
Pancreas
Leukemia mononuclear
Salivary glands
Leukemia mononuclear
Stomach, forestomach
Leukemia mononuclear
Stomach, glandular
Leukemia mononuclear
Tongue
Papilloma squamous
Tooth .
Pulp, leukemia mononuclear
CARDIOVASCULAR SYSTEM
Heart
Leukemia mononuclear
ENDOCRINE SYSTEM
Adrenal gland, cortex
Adenoma
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochromocytoma malignant
Pheochromocytoma complex
Pheochromocytoma benign
Bilateral, pheochroinocytflma benign
Islets, pancreatic
Leukemia mononuclear
Parathyroid gland
Leukemia mononuclear
Hyclroqcainone, NTP TR 366
66
Low Dose
High Dose
65
65
55
65
65
55
(53)
1 (2%)
(55)
Y (2%)
(55)
1 (2°Jo)
(55)
*(55)
(54)
I (2%)
*(55)
(54)
*(55)
65
55
*(55)
*(55)
fl (23'0)
*(55)
(bb)
15 (27g'a)
"t55?
5 (9%)
(55)
1 (2%)
(55)
2 (49'0)
*(55)
t (2Wo)
(5b)
Y
'°(55)
2
*(55)
Y
*(5b)
2
(55)
'1(55)
*(5b)
3 (5%)
(55)
5 (9%)
*(55)
fl (2~'0)
*(55)
(55)
6 (11%)
(54)
& (11%)
1 (29b)
9
(55)
S
i
fl
2 (4%)
(296)
(23'0)
(2%)
(4%)
'°(55)
7 (13%)
(55)
(16°h)
(1b%)
(2%)
(2%)
(53)
P (2%)
*(55)
(54)
*(5b)
132
(4%)
(4~Po3
(29b)
(5%)
(6%)
1 (2%)
1 (2%)
(55)
9 (16%)
*(55)
3 (5%)
.~
(53)
2
(54)
2.
(51) .
1
(5b)
3:
(53)
3
(51)
1
]
1
(55)
22
*(55)
8
(29u)
(2%)
(2%)
(409b)
(15%)
1 (2%)
(55)
4 (7%)
(55)
4 (7%)
(54)
4 (79'a)
(54)
4 (7%)
*(5b)
'°(55)
5 (99b)
(55)
13 (24qo)
(55)
1
14
(b4)
12
1
(2%)
(25°k)
(22%)
(23°a)
4 (7%n)
(65)
1 (2%)
(54)
i (2%)
.
TABLE Bi, SUMMARY OF THKINCrDExcE OF NEoPLAsMS IN FEMALE RATS IN THE TWO-YEAR
GAvaGE STUDY OF HYDttOQcnNONE°(contanuea)
.
ENDOCRINE SYSTEM (Continued)
Pituitary gland
Leukemia mononuclear
1lSenengioma malignant, metastatic
E'srs distalis, adenoma
Pars distalis, carcinoma
Pars distalis, leukemia mononuclear
Thyroid gland
Leukemia mononuclear
Bilateral, C-cell, adenoma
C-cell, adenoms .
C-cell, carcinoma
.
Follicular cell, adenocarcinoma
Folli~ular cell, adenoma
Vehicle Control.
(54)
4 (7'9b)
23 (43%)
i (2%)
~
(55)
2
1
8
4
1
(23b)
(2%b)
(154'0)
('79'0)
(2%)
.
.
LOW Dose
. .
(54)
1 (2°k)
21 (39%)
1 (29~0)
2 (43'0)
(54)
3
1
1
1
(&%)
(2%)
(2%)
(2%a)
High ' D050
(54)
8 (159'0)
1 (2%)
16 (30R'o)
1 (2~°0)
(Sb)
1 (2%)
5 (9%)
3 (5°k)
GENERAL BODY SYSTEM
None
GENITAL SYSTEM
Clitoral gland
Adenoma
Leukemia mononuclear
Ovary
(sranulosa cell tumor malignant
Leukemia mononuclear
I.taLQOma
Oviduct
Leukemia mononuclear
Uterus
I.eiomyosarcoma
Leukemia mononuclear
Polyp stroanal
Bilateral, polyp stromal
Endometrium, adenocarcinoma
Endoemetrium, sarcoma stromal
Vagina
Squmnous cell carcinoma
HEMATOPOIETIC SYSTEM
Blood
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lymph node
Axillary, leukemia mononuclear
Deep cervical, leukemia mononuclear
Inguinal, leukemia mononuclear
Lumbar, leukemia mononuclear
hiediastinal, leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, mandibnlar
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear ~
Spleen
Leukemia mononuclear
Thymus
Leukemia mononuclear
(51)
4
1
(55)
1
2
*(55)
*(55)
3
2
*(55)
1
3
I
*(55)
(b5)
(55)
(8%)
(29b)
(2~°0)
(4%)
(52)
9 (17g'o)
2 (4%)
(b5)
(5'3'0)
(4'Yo)
(2%)
(53b)
(29'0)
8 (153°0)
*(5b)
g (2%)
(5b)
1 (29'o)
*(55)
2
5
1
1
1
'"t551
*(55)
7 (13%a)
(65)
5 (9%)
(55)
*(55)
fi (15%)
*(55)
7 (13%)
*(55)
3 (5w)
12 (22%)
(49"0)
(9't''o)
(29'0)
(2%)
(296)
4 (7%)
9 (16%)
*'(55)
1 (2%)
2 (496)
3
3
(55)
6
(53)
7
(55)
3
(52)
6
(5%)
(5%)
(9%)
(13%)
(16%)
(1.2°/a)
133
3
2
*(5b)
5
*(55)
8
G55?
15
*(55)
6
t53'o9
(4%)
(9~"0)
(15%)
(27%)
(1I%)
'°(b5)
15
(bb)
11
(55)
1
1
3
2
6
4
(52)
13
(54)
16
(55)
22
(51)
9
(27%)
(20%)
(2%)
(23'0)
(5~'0)
(4%)
(11%)
(7%)
(25%)
(3030)
(40%)
(1$R'o)
Hyciroqtainone, NTP Tii, 366
TABLE Bi : SUMMARY- OF THE INCIDENCE OF NEOPLASMS IN FEMALE RATS IN THE TWO-YEAR
GAVAGE STUDY OF HYDROQUINONE (Continued)
Vehicle Control
FNTEG
NTARY SYSTEM
Mammary gland
Adenocarcinoma
Adenor,arcinoma, multiple
Adenoma.
Fibre>adenoma
Fibraadenoma, multiple
Leukemia mononuclear
Skin
Basal cell adenoma
I{eratoacanthoma
Papilloma squamous
Subcutaneous tissue, leukemia mononuclear
Subcutaneous tissue, sarcoma
MUSCULOSKELETAL SYSTEM
Bone
Cartilage, adenocarcinoma, extension,
metastatic, thyroid gland
Skeletal muscle
Leukemia mononuclear
Pheochromacytoma malignant, extension,
metastatic, adrenal gland
NERVOUS SYSTEM
Brain
Asteocytoma malignant
Leukemia mononuclear
Meninges, leukemia mononuclear
lUlen3nges, Yneningioma malignant
Pons, carcinoma, metastatic
Spinal card
Leukemia mononuclear
Meninges, leukemia mononuclear
RESPIRATORY SYSTEM
Lung
Alveolar/bronchiolar carcinoma
Carcinoma, metastatic, thyroid gland
Leukemia mononuclear
F'heochromocytoma malignant, metastatic,
adrenal gland
Nose
Leukemia mononuclear
Trachea
Leukemia mononuclear
SPECIAL SENSES SYSTEM
Zymbai gland
Carcinoma
URINARY SYSTEM
Kidney
Leukemia mononuclear
Urinary bladder
Leukemia mononuclear
IIydroqugnone,NTP TR 366
(55)
2 (4%)
1 (2%)
28 (51%)
1 (2%)
3 (59b)
(5b)
3 (5%)
(54)
Low Dose
f55)
_
2 (43`0)
22 (40°10)
*(55)
Y (2 51.)
1 (29b)
3 (5%)
*(55)
*(55)
i (2%)
1 (29b)
*(5b)
1 (2%)
High Dose
(54)
1 (2%)
21 . (39%)
1 (2%)
3 (69'0)
(55)
2 (4%)
' .L (2%a)
4 - (73'0)
g (2%)
(55)
*(55)
1 (2%)
1 (2%)
(56)
(55)
2 (4%)
3 (590)
*(55)
1 t2%3
3 (5°!0)
1 (29b)
1 (2%)
*(S5)
1 {BR6}
2 (4%)
*(55)
1 (2°l0)
1 (2%)
*(55)
(56)
*(55)
1 (2~'0)
6 (ll%)
(55)
5 (9g'o)
(65)
*(55)
6 (il%)
*(55)
3 (5%)
*(55)
"`(55)
(5b)
6 (11%)
(55)
4 (7%)
134
(55)
EO (18'Yo)
*(5b)
3 (5%)
4 (7%)
1 (2%)
8 (Y6%)
(55)
1 (2°fo)
2 (2%)
15 (27%)
1 (2%)
(55)
6 (1 1%)
(b5)
2 (4%)
*(55)
1 (2%)
(55)
16 (29%)
(51)
8 (16%)
.
TABLE BY . SUMMARY OF THE INCIDENCE OF NEOPLASIVIS IN FEMALE RATS IN THE TWO-YEAR
GAVA(aE STUDY OF glYfl.lROQUiNQ9riE (Continued)
,
SYSTEMIC LESIONS
Multiple organs ,
Leukemia mononuclear
ANIMAL DISPOSITION SUMMARY
Animals initially in study
Terminal sacrifice
Moribund, .
Interval sacrifice
Dead
~'.avage death
Accident
TUMOR SUMMARY
Total animals with primary neoplasms
Total primary neoglasms
Total animals with benign neoplasms
Total benign neoplasms
Total animals with malignant neopissaxas
Total malignant neoplasms
Total animals with secondary neogalasens `~°°~'
Total secondary neoplasms
Vehicle Control .
Low Dose
High Dose
*(5b)
9 (16Ro)
"(55)
15 (27%)
*(5S)
22 (403°0)
66
39
14
10
2
47
100
44
79
18
21
fl
1
65
27
19
10
6
g
65
31
14
10
6
49
89
41
63
24
26
1
1
50
1.04
42
69
32
35
3
5
g
.
'~ Number ofanimals receiving complete necropsy examination; all gross lesions including masses examined microscopically
Primary tumors: all tumors except secondary tumors
°°"* Secondary tumors : rnetastatic tumors or tumors invasive into an adjacent organ
135
Hydroquanone,lVTF''I°R,.366
TABLE B2.
.
.
INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS IN THE TWO-YEAR
GavAcE STUDY OF HYDROQUINONE : VEHICLE CONTROL
WEEK
STUDY
N
.
CARCASS
ID
A7 .
ENT
Y SYSTEM
Esophagus
Intestine large
Intestine large, cecnm
Leukemia mononuclear
Intestine large, colon
Leukemia mononuclear
Intestine large, rectum
Leukemia mononuclear
Intestine small
Intestine small,duodenum
Intastine small, ileum
Leukemia mononuclear
Intestine small ; jejunum.
Leukemia mononuclear
Liver
.
Leukemia mononuclear
Mesentery
Leukemia mononuclear
Pancreas
-
.
0
6
8
0
7
2
0
7
2
0
7
9
0
8
3
0
9
3
0
9
3
0
9
4
0
9
7
0
9
8
0
9
8
1
0
1
1
0
2
1
0
4
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1.
0
5
1
0
5
1
0
5
--42
5
2
4
4
0
5
4
0
4
4
5
4
4
2
4
4
3
5
4
8
4
4
3
4
4
9
4
5
2
3
5
0
5
4
1
4
5
0
4
4
0
3
4
0
2
4
2
3
4
4
4
4
5
1
4
5
2
4
5
3
6
3
8
2
8
3
9
3
+
+
h
t
+
+
-f
+
+
+
+
t
+
+
+
+
+
t
+
+
+
+
+
+
. ..
+
+
+ A
.
+
+
+
+
+
+ +
.. .
+ +
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-F
a-
+
+
+
+
+
+
X
+
.
..
+
+
+
+
+
+
-h
+
+
+
+
+
+
.
..
+
+
+
.
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+;
+
+
+
+
+
+
+
+
-i-
+
+
+
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+
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+
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+
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+
X
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+
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+
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%
+
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+
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t
+
X
+
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+
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+
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+
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.
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+
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%
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.
+
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.
Leukemia mononuclear
Salivary glands
. Leukemia mononuclear
Stomach
Stomach, forestomach
Leukemia mononuclear
Stomach, glandular
Tooth
Pulp, leukemia mononuclear
CAR)IOVASCULAR. SYSTEM
Heart
Leukemia mononuclear
0
5
4
-
ENDOCRINE SYSTEM
Adrenal gland
Adrenal gland, cortex
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochromocytoma malignant
Phoochmmocytoma benign
Islets, pancreatic
Parathyroid gland
Pituitary gland
Leukemia mononuclear
Parsdistalis,adenoma
Pars distalis, carcinoma
Thyroid gland
Leukemia mononuclear
Bilateral, C-cell, adenoma
Gcell, adenoma
C-cell, carcinoma
Follicular cell, adenocarcinoma
-6^
-F
.
.
i-
-F
.
+
+
.+
+
+
+
+
+
+
-1+
+
+
+
+
+
+
+
+
+
+
-4~
+
+
i-
f
+
+
+
+
+
+
+
X
+
%
+
+
X
+
+
+
-t-
+
+
X
+
X
+
~F
+
+
+ . +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
%
.
7i
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ +
+ +
X R
+ +
% .7C
+
+
,-
+
+
X
+
+
+
+
+
+
X
+
X.
+
.
+
+
+
+
+
+
+
R
+
+
ii-
+
.+
+
M
+
+
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+
+
+
.
+
-i-
+
.
+,
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
R
R
X
+
+.
-F
X
+
+
+
X
.
i
+
X
R
%
R
R
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
+
+
7C
+
X
+
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1
0
5
X
+
X
+
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R
+
+
+
ft
+
X
.
R
.
+
R
A
R
R
X
%
%
GENERAL BODY SYSTEM
None
GENITAL SYSTEM
Clitoral gland
Adenoma
Leukemia mononuclear
Ovary
1iP3IIUlOSH C011 tumor malignant
Leukemia mononuclear '
Uterus
Leukemia mononvclear
Polyp stmmal
Endometrium, sarcoma stromal
Vagina
M
.
.
+
+
+
+
+
+
+
+
+
+
+
M
+
+
+
.
+
+
+
+ .+
+
X
+
+
+
X
7C
X
R
+
.
3
+
+
%
+
+
X
+
R
+
+
136
+
k
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
%
M:
A
X:
+
+
R
R
+
+ : Tissue examined microscopically
: Not examined
- : Present but not examined microscopically
I: Insufficient tissue
Hydroquinone,lVTP T1Z 366
+
Missing
Autolysis precludes examination
Incidence of listed morphology
X
X
+
+
+
R
+
TABLE BI INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS- VEHICLE CONTROL
(Continued)
wEExs ox
1
STUDY
CARCASS
III
Esophagus
intestine large
Leukemia mononuclear
Intestine large,colon
Leukemia mononuclear
Intestine large, rectum
Leukemia mononuclear
Intestine small
Intestine small,duodenum
Intestine small, ileum
Leukemia monormclea
Intestine small, jejuaurit
Leukemia mononuclear
Liver
Leukemia mononuclear
Mesentery
Leukemia mononuclear
Pancreas
Leukemia mononuclear
Salivary glands Leukemia mononuclear
.
Stomach
Stomach, forestomach
Leukemia mononuclear
Stomach, glandular
Tooth
Pulp, leukemia mononuclear
~
1
1
1
1
1
1
1
1
1
1
1
0
5
0
5
0
5
1
1
0
5
0
5
1
1
1
0
5
0
5
4
1
1
1
1
0
5
0
5
-570
1
3 5
2
2
1
2
1
3
3
1
3
2
3
3
4
2
4
3
6
2
0
2
1
2
1
3
1
4
0
1
1
1
2
1
2
2
4
1
6
1
7
1
7
2
7
3
8
1
0
5
+
+
Intestine large, eecnm
Heart
1
9
5
SYSTEM
Leukemia mononuclear
ENDOCRINE SYSTEM
Adrenal gland
Adrenal gland, cortex
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochromocytoma malignant
Pheochromocytoma benign
Islets, pancreatic
Parathyroid gland
Pituitary gland
Leukemia mononuclear
Pars distalis, adenoma
Pars distalis, carcinoma
Thyroid gland
Leukemia mononuclear
Bilateral, C-cell, adenoma
GcaCl, adenoma
Gcell, carcinoma
Follicular cell, adsnocarcinoma
.
,
.
,
.
'.
..
.
-
.
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
1
0
5
0
5
0
5
0
5
1
+
A
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
¢
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
-F
+
+
. +
+
+
+
t
+
+ . +
+
+
+- +
.
+
+
+
d-
t
+
+
+
+
+
+
+
+
+
+. +
.+
+
+
+
.
+
+
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+
+
+
+
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+
+
+
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+
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A
+
+
+
+
+
+
+
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+
+
+
+
+
+
+
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t
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+
+
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+
+
+
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+
+
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+
+
+
+
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+
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+
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+
+
+
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+
+
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+
+
+
+
+
+
+
+
+
+
+
+
+
+
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+
+
+
+
+
+
+
+
.
+
+
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+
+
+
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+
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+
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+
.
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+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
.
+
+
+
.
+
x
.
+
+
+
+
+
X
+
+
+
+
+
+
+
+
+
%
R
X
+
+
+
+
t
+
+
+
+
+
+
+
+
+
A
+
+
+
i+
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+
+
+
X
A
t
+
+
+
+
t
t
+
+
+
+
+
+
+
+
+
+
+
+
M
+
+
+
+
+
+
X
+
.
+
+
+
+
+
¢
+
+
R
+
M
+
+
+
+
7E
%
X
%
%
+
+
+
+
+
X
X
X
+
d-
+
+
h
7t
+
+
+
R
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
.
°
+
+
+
X
GENERAL BODY SYSTEM
None
SYSTEM
Clitoral .gland
Adenoma
Leukemia mononuclear
Ovary
Granutosa call tumor malignant
Leukemia mononuclear
Uterus
Leukemia mononuclear
Poiyp stromal
Endometrium, sarcoma stromal
Vagina
+
Ni
+
+
+
+
+
R
+
+
+
+
i
+
+
+
+
+
+
M
+
+
+
+
+
+
+
+
-F
+
+
+
t
+
+
+
+
+
.
+.
+
+
+
+
.
+
+
+
t
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
A
+
+
+
+
X
X
%
f
137
X
.
Hydroquinone, NTP'TR 366
TABLE B2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS- VEHICLE CONTROL
(Continued)
WEEKS
STUDY
N
CARCASS
ID
ALIMENTARY SYSTEM
Esophagus
later
large
Intestine large,cecum
Leukemia mononuclear
Intestine large, colon
Leukemia mononuclear
Intestine large, rectum
Leukemia mononuclear
Intestine small
Intestinesmall,duodenum
lot
estinesmall,ileura
Leukemia mononuclear
Intestine small;jejunum
Leukemia mononuclear
Liver'
Leukemia mononuclear
Mesentery
Leukemia mononuclear
Pancreas
Leukemia mononuclear
Salivary glands
Leukemia mononuclear
Stomach
Stomach, forestomach
Leukemia mononuclear
Stomach, glandular
Tooth
Pulp, leukemia mononuclear
CARDIOVASCULAR SYSTEM
Heart
Leukemia mononuclear
DOCRINE SYSTEM
Adrenal gland
Adrenal gland, cortex
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochromocytoma malignant
Pheochromocytoma benign
Islets, pancreatic
Parathyroid gland
Pituitary gland
Leukemia mononuclear
Pars disYalis, adenoma
Pars distalis, carcinoma
Thyroid gland
Leukemia mononuclear
Bilateral, C-cell, adenoma
C-cell, adenoma
C-call, carcinoma
Follicular cell, adenocarcinoma
tta
None
1
0
5
1
0
5
1
0
5
2
0
5
1
0
5
9
1
9
2
4
1
1
1
2
1
TOTAL :
TISSUES
TUMORS
55
.~5
53
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-tr
+
+
+
+
+
55 .
s+
+
+
+
+
+
+
+
+
+
+
+
t
+
55
55
54
+
+
+
+
+
+
+
¢
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
3-
+
+
+
+
+
+
+
+
+
+
¢
+
+
+
+
+
+
55
55
+
+
+
+
+
54
+
+
+
+
+
+
+
+
+
+
-I+
+
+
.+
+
+
,
S5
'
.
X
+
.
.
.
+
.
.
+
+
+
54
.
~
,
55 `
7
.
.
.
55 .
55
SS
55
1
55
-
.
. -
-
55
1
53
54
23
X
+
,
55
+
K
1
m
Clitoral gland
Adenoma
Leukemia mononuclear
Ovary
Granulosa cell tumor malignant
Leukemia mononuclear
Uterus
Leukemia mononuclear
Polyp stromal
Endometrium,sarcoma stromal
Vagina
+
±
i-
+
+
+
i.
~. .
+
+
51
4
1
55
+
+
-!-
+
+
55
X
X
HydTOq111T10Tley NTP '1'R 366
12
2
138
TABLE B2 . INDIVIDUAL ANIMAL ItMOR PATHOLOGY OF FEMALE RATS: VEHICLE CONTROL
(Continued)
WEEKS ON
STUDY
CARCASS
ID
EMATOPOIETIC SYSTEM
Blood
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lymph node
'
Inguinal, leukemia mononuclear
Mediastinal,laukamia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, ma¢dibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
Spleen
~ Leukemia moaonnclear Thymus
Leukemia mononuclear
.
TEGUMENTARY SYSTEM
Mammary gland
Adenocarcinoeaa
Adanocarcinoma, multiple
Ffibroadenoma
Fibroadenoma, multiple
Leukemia mononuclear
0
6
8
0
7
2
0
7
2
0
7
9
0
8
3
0
9
3
0
9
3
0
9
4
0
9
7
2
5
2
4
0
5
0
4
5
4
2
4
3
5
8
4
3
4
9
4
2
3
+
+
+
+
+
%
+
X
+
+
+
X
+
+
+
X
+
x
+
+
+
+
+
+
+
+
+
r
+
+
+
+
M
+
+
+
+
%
+
X
+
X
+
X
+
+
+
+
+
X
.
Skin
t . +
Subcutaneous tissue, leukemia
mononuclear
+
X
+
X
+
%
+
%
+
X
+
+
+
+
+
+
+
+
+
X
X
+
+
.
k
+
+
+
+
+
+
%
+
+
+
+
+
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
+
. +
+
+
+
+
+
+
+
+
+
+
1
Q
5
1
0
5
1
0
5
1
0
5
1
0
5
- 1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
0
5
1
4
Q
4
0
3
0
2
2
3
4
4
5
1
5
2
5
3
6
3
8
2
8
3
9
3
r
+
+
+
IC
+
X
+
+
+
t
+
+
+
+
-i-
+
+
%
+
+
-"r
7C
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
X
X
+
i-
+
r
+
+
+
+
+
+
+
+
+
+
+
M
R
X
+
+
X
+
+
R .
+
+
R
+ +
X
+
+
+
+
+
X
. i-
i-
+
X
i-
+
+
X
+
X
+
x
+
%
+
+
X
t
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
%
o--
+
+
+
+
+
+
+
+
+
+
+
+
+
+
%
Yvf
+
+
.
+
+
+
+
+
+
X
X
X
X
t
i-
+
g
X
X
;-
t
+
+
t
t
+
+
X
t
+
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
R
+
+
+
+
+
+
+
+
+
+
+
.
+
+
X
X
+
+
+
,-
+
+
+
i-
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
i-
+
+
f
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
%
+
X
X
+
X
+
+
X
+
+
X
+
X
+
+
R
+
X
X
+
X
+
1
Q
4
X
+
+
+
-(1 - 0
9
9
8
8
Y
+
+
+
X
1 1
0
0
1
2
X
X
+
Nose
Leukemia mononuclear
Trachea
+
+
%
+
X
+
%
+
IC
Y
RESPIRATORY SYSTEM
Lung
Leukemia mononuclear
+
R
Bone
Skeletal muscle
Leukemia mononuclear
NERVOUS SYSTEM
Brain
Leukemia mononuclear
Meninges,leukemia mononuclear
Pons, carcinoma, metastatic
Spinal cord
Leukemia mononuclear
IIReninges, leukemia mononuclear
Q
5
4
X
X
+
7C
X
X
+
-
+
+
SPECIAL SENSES SYSTEM
Eye
Harderian gland
URINARY SYSTEM
Kidney
Leukemia mononuclear
Urinary bladder
Leukemia mononuclear
-
+
+
139
+
X
+
R
+
x
+
X
+
+
Hydroquinone, NTP `I'R-366
TABLE B2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS : VEHICLE CONTROL
(Continued)
WEEK
STUDY v+
CARCASS
ID
HEMATOPOIETIC S,
Blood
Leukemia mononuclear
1
0
5
1
0
5
1
0
5
2
0
5
I
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
I
0
5
1
0
5
1 1
0
0
5
5
I-,
0
5
I
0
5
1
0
5
10
5
1
0
5
.1
0
5
1
0
5
1
0
5
1
0
5
I
0
5
0
3
1
5
2
2
1
2
1
3
3
1
3
2
3
3
4
2
4
3
6
2
0.
2
1
2
1
3
0
1
1
1
2
1
2
2
4
1
6
1
7
1
7
2
7
3
1
+
1
4
+
+
+
Bone marrow
Leukemia mononuclear
Lymph node
Ioguinal, leukemia mononuclear
Med7astinal,leuksmia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, mandibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
Spleen
Leukemia mononuclear
Leukemia mononuclear
INTEGUMENTARY
Mammary gland
Adanocarcinoma
Adenocarcinoma, multiple
Fibroadenoma
Fibroadenoma, multiple
Leukemia mononuclear
Skin
Subcutaneous tissue, leukemia
mononuclear
MUSCULOSKELET
Bone
Skeletal muscle
Leukemia mononuclear
+
t-
+
+
+
..
.
+
+
+
-F
fr
.
+
+
+
+
+
+
+
+
+ . + . . +.
+ .
+
X
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
fr
+
-F
-i-
+
+
i-
-r
+
+
i-
+
+
t
-h
+.
+
-F
+
+
+
+
+
+
+
+
+
+
+
.. .
M
+
+
+
+
+
+
+
+
+
+
+
-+
.
+
+
'+
+: +
A:
X
A
.
i-
.
+
+
+
+
+
+
-F
+
+
+
+
,t
+
+
+ . +
+
+
+
+
+
+
+
+
+
. . .
+
X
+
+
+
+
+
.
+
+
+
+
+
.
+
+
+
+
+
-h
+
i-
+
+
+
+
+
4-
+
+
+
+
+
+
+
+
+
+
+
i-
+
+
+
X
X
X
X
X
X
X
R
R
R
+
+
+
-0-
+
+
+
+
+
+
-F
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+_
+
-+ .
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
i-
t-
+
+
+
-0-
+
+
+
.
+
+
+
'r
+
+
+
+
+
+
+
Leukemia mononuclear
Meninges, leukemia mononuclear
Pons, cantinoma,meCastatic
Spinal cord
Leukemia mononuclear
Meninges,leu ..emia mononuclear
+
%
+
+
+
+
+
+
+
X
Lung
Leukemia mononuclear
Nose
Leukemia mononuclear
Eye
SPECIAL SENSES SYSTEM
+
+
.
Brain
Trachea
+
+
+
+
Thymus
8
1
0
5
-
.
,
-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-F
+
+
+
+
+
t
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-h
+
+
f
.
+
+
+
t
+
+
+
+
+
+
i-
+
t
+
+
+:
+
+
+
+
+
+
+
+
+
.
+.
+
Harderiaa gland
Kidney
.
Leukemia mononuclear
Urinarybladder
Leukemia mononuclear
Hydroquinone, NTP TR 366
`
+
+
.
.
+
+
i-
140
+
.
+
+
+
+
+
+
t
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
a
TABLE Bi INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS : VEHICLE CONTROL
(Continued)
f
f
r
WEEKS ONSTUDY
1
0
5
1
0
S
1
D
5
1
0
5
1
Cs
5
CARCASS
ID
4
9
1
4
9
2
5
0
1
5
1
1
5
2
i.
+
+
+
+
'+
+
r
+
+
+
fr
+
-r
+
+
+
+
-I-
+
+
+
+
i-
gs
+
+
+
~
-!-
52
+
+
+
i_
%
X
X
+
+
+
+
t-
+
Blood
Leukemia mononuclear
Hone marrow
Leukemia mononuclear
Lymph
14!uinal
di.stmal
node
.leukerniamonorraclear
leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, maudibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
Spleen
Leukemia mononuclear
Thymus
Leukemia mononuclear
Mammary gland
Adenxarcinoma
Adsnacarcinoma, multiple
Fibroadenoma
k°ibroadeaoma, multiple
Leukemia mononuclear
Skin
Subcutaneous tissue, leukemia
mononuclear
MUSCULOSKE
Bone
Skeletal muscle
Leukemia mononuclear
Brain
Leukemia mononuclear
Meainges, leukemia mononuclear
Pons, carcinoma, metastatic
Spinal cord
Leukemia mononuclear
Meningas, leukemia mononuclear
RESPIRATORY SYSTEM
Lung
Leukemia mononuclear
Nose
Leukemia mononuclear
Trachea
-t-r
.
TOTAL:
TISSUES
TUMORS
.
.
'
55
.,
.
55
2
55
.
53
SS
F
1
28
+
-r
55
+
,
54
I
. +
+
+
+
-1
-
55
-
_
g
.
+
+
+
+
-+
+
+
+
+
-1-
+
+
+
+
-7-
+
+
+
+
-t
+
i-
+
+
-r
.
-
55
g
55
g
55
Harderian gland
Kidney
Leukemia mononuclear
Urinary bladder
Leukemia mononuclear
55
g
55
q
141
Hydroqczgnone, NTF''Pii, 366
TABLE B2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS IN THE TWO-YEAR
GAVA(xE STUDY ()I+ HYDROQUINONE : LOW DOSE
-
WEEKS 014
STUDY
CARCASS
TD
ALIMENTARY SYSTEM
Esog'aagus
Intestine large
Intestine large, cecum
Intestine large, colon
Intestine large, rectum
Leukemia mononuclear
Intestine small
Intestine small,duodenum
Intestine small, ileum
InCestina small, jejuaum
Liver
Leukemia mononuclear
Mesentery
Leukemia mononuclear
Pancreas
Pharynx
Salivary glands
Leukemia mononuclear
Stomach
Stomach, £orestomach
Leukemia mononuclear
Stomach, glandular
Leukemia mononuclear
Tongue
Papilloma squamous
Toath
Pulp, leukemia mononuclear
4
5
4
0
6
4
0
7
0
0
7
1
0
8
0
0
8
3
0
8
5
0
9
0
0
9
0
0
9
0
0
9
1
0
9
4
0
9
4
0
9
4
0
9
5
0
9
6
0
9
6
0
9
6
0
9
6
1
0
0
1
0
0
1
0
0
1
0
2
1
0
2
1
0
2
5
3
5
6
0
5
5
4
5
6
4
4
5
8
5
5
6
5
5
4
4
5
8
4
5
7
5
5
8
3
6
1
5
6
2
5
5
7
4
6
-1
*4
6
5
5
5
7
3
6
3
3
53
2
6
5
4
5
9
4
6
2
2
6
2
3
6
1
3
6
4
3
0
4
+
+
+
+
i-
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
A
-t+
+
+
1
A
+
+
+
A
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
±
. .
a+
+
+
.
+
+
+
+
+ '
+
+
+
+
+
+
+
+
+
+ ~
+
+
-F
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ +
+ +
+ +
. . .
+ +
. . .
+ +
+ -I. .A
a- +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-h
+
+
+
+
+
A
A
t
+
A
A
t
+
A
A
+
t
+
.
+
+
tr
+
+
+
+
+
-F
+
+
+
+
+
+
+
+
+
i~
+
+
+
+
+
+
+
+
+
+
.
+
. .
+
+
+
.
+
+
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
R
iX
IG
R .
+ .
X
+
R
+
%
R
R
+
-
+
+
+
.
+
t
+
+
+
M
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
Adrenal gland
Adrenal gland, cortex
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pbeochromocytoma malignant
Pheochmmocytoma complex
Bilateral, pheochromocrytoma benign
Islets, pancreatic
Parathyroid gland
Pituitary gland
Leukemia mononuclear
Pars distalis, adenoma
Pars distalis,carcinoma
Pars distalis, leukemia mononuclear
Thyroid gland
C-celi, adenoma
C-cell, carcinoma
Follicular cell, adenocarcinoma
Follicular cell, adenoma
+
R
+
%
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
R
+
-i-
+ . +
+
.
+
+
+
+
+
+
+
+
+
+
+
+
,r
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
a-
+
+
+
+
-t
X
i%
-7-
.-F . + ~ +
.
+
.
+
t
+
+
+
+
+
+
+
+
+
+
+
..
t
+
+
+
+
+
-1-
+
+
+
+
%
~
+
+
+
+
+
+
+
+
+
+
+
°.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-
+
+
+
.
+
4
+
+
+
+
.
+ .+
.
+
+
.
+
+
X
+
+
X
+
+
%
+
+
+
X
+
+
X
+
+
+
+
+
+
+
%
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
.
+
+
+
+
+
+
+
X
+
7C
+
+
+
+
+
X
+
%
+
+
+
+
+
X
+
X
+
+
+
+
+
X
t
%
+
+
+
+
+
X
+
%
-
+
+
+
+
+
X
+
X
+
+
+
+
+
+
+
+
+
4M
+
M
+
+
M
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
M
+
+
+
+
+
M
+
+
+
+
+
+
+
+
+
+
+
M
+
+
+
+
R
X
R
R
+
+
.
%
+
X
+
+
R
+
-r
+
+
+
.
+
X
+
+
¢
X
+
+
+
X
+
+
+
X
+
+
lC
+
R
+
-F
=DIOVASCULAR SYSTEM
Heart
Leukemia mononuclear
+
+
+
A
A
+
+
+
t-
+
X
+
+
%
-r
+
+
+
+
X
+
+
X
+
+
X
X
GENE RAL BODY SYSTEM
None
SYSTEM
Clitoral gland
Adenoma
Leukemia mononuclear
Ovary
Graaulosa call tumor malignant
Leukemia mononuclear `
Luteoma
Uterus
Leiomyosarcoma
Leukemia mononuclear
Polyp stromal
Bilateral, polyp stromal
Endometrium, adenocarcinoma
Endometrium, sarcoma stromai
Vagina
Hydrocguinoney NTP TR 366
-F
+
1WI
+
I12
+
'r
+
-F
+
+
X
+
}
+
+
+
X
X
+
X
+
+
%
+
+
+
+
-I-
X
7C
}
+
t
+
i-
-S-
+
+
+
+
+
}
t
.
t
t
t
t
t
+
+
+
X
+
M
t
+
+
+
+
-F
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
R
+
X
+
R
X
%
+
X
,
-----
142
+
X
+
-
.
TABLE B2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS: LOW DOSE
(Continued)
WEEKS ON
i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
STUDY
4
0
0
0
0
0
0
0
CARCASS
ID
,
ALIMENTARY SY
EsoPh aB~
Intestina large
Intestine large, cecum
Intestine larga,colon
Intestine large, rectum
Leukemia mononuclear
Intestine small
Intestine small, duodenum
Intestine small, ileum
Intestine small, jejunum
Liver
Leukemia moaonuclear
Mesentery
Leukemia mononuclear
Pancreas
Pharynx
Salivary glands
Leukemia moaonuclear
Stomach
Stomach, foeestomach
Leukemia morionuclear
Stomach, glandular
Leukemia mononuclear
0
5
1
0
5
111
0
0 4
5
5
5
4
2
4
1
5
1
6
1
0
6
2
6
3
+
+
+
+
+
+
3
4
5
5
5
0
5
5
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
9
3
3
1
5
2
7
2
0
3
2
1
1
2
2
1
3
2
5
1
5
2
5
3
4
2
4
3
6
4
7
1
0
2
3
1
4
1
+
+
A
+
.
+
+
+
+
+
+
+
+
+
.
+
+
+
A
+
.
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
X
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
.
1
3
.,.
+
+
M
+
+
+
+
+
+
+
+
+
X
+
+
+
X
+
+
+
a-
Tongue
+
+
t
+
R
+
+
.
-
Papilloma squamous
Tooth
Pulp, leukemia mononuclear
CARDIOVASCULAR SYSTEM
Heart
Leukemia mononuclear
.
ENDOC RINE
STEM
Adrenal gland
Adrenal gland, cortex
Leukemia monoauclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochmmocytoma malignant
Pheochromocytoma complex
Bilateral, pheochromocytoma benign
Islets, pancreatic
.
Parathyroid gland
Pituitary gland
Leukemia monoauclear
Parsdistalis,adenoma
Pars distatis, carcinoma
Pars distalis, leukemia mononuclear
Thyroid gland
Gce1l, adenoma
C-cell, carcinoma
Follicular cell, adenocareinoma
Follicular cell, adenoma
N RA
None
DY
YS
+
-i-
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
.
+
i-
+
M
+
+
+
+
+
+
X
%
X
+
+
+
.
+
Y
+
M
+
+
+
+
+
+
+
+
+ - +
+
+
+
+
+
+
+
+
+
+
+
X
-F
i+
+
i-
+
,
M
.
.
X
+
+
g
+
+
+
+
M
+
R
R
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
X
X
X
+
+
+
+
M
+
+
+
+
.
X
X
X
+
+
+
+
+
+
+
+
-
M
1A
+
X
Ovary
+
-E
+
+
+
+
Graaulosa cell tumor malignant
Leukemia mononuclear
Luteoma
Uterus
Leiomyosarcoma
Leukemia mononuclear
+
+
;;
GENITAL SYSTEM
Clitoral gland
Adenoma
Leukemia mononuclear
+
+
X
+
g
+
g
M
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Polyp stromal
Bilateral, polyp stromal
Endometrium, adenocarcinoma
Endometrium, sarcoma stmmal
Vagina
.
143
I-IydrOqUlnOne, NTP TR. 366
TABLE B2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS: LOW DOSE .
(Continued)
WEEK ON
STUDY
CARCASS
ID
ALIMENTARY SYST
Esophagus
Intestine large .
Intestine larga,cecum
Intestine large, colon
Intestine large, rectum
Leukemia mononuclear
Intestine small
Intestine small,duodenum
Intestine small, ileum
Intestina small, jejuaum
Y
0
5
.
1
0
5
1
0
5
1
0
5
1
0 .
5
-5 - 5-5- 5
8
8
9
9
1
2
1
2
-TOTAL:
TISSUES
TUMORS
6
0
1
28
28
24
26
28
.
. .
Liver
-
.
+
Leukemia mononuclear
Mesentery
Leukemia mononuclear
Pancreas
.
.
. .
Pharynx
Salivary glands
.
Leukemia mononuclear'
Stomach
Stomach, Eorestomach
Leukemia mononuclear
Stomach, glandular
"
+
+
X
~
.
+
.
+
X
.
.
.
-
.
.
28
,Zg
24
23
,
-
55
.
~15
is
g
28
1
26
L
28
28
I
28
.
.
.
Leukemia mononuclear
Tongue
Papilloma squamous
Tooth
Pulp, leukemia mononuclear
-
CARDIOVASCULAR SY6'rk;M
Heart
Leukemia mononuclear
NDOCRINE SYSTEM
Adrenal gland
Adrenal gland, cortex
.
Leukemia. mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochromocytoma malignant
Pheochmmocytoma complex
Bilateral, pheochromocytoma benign
Islets, pancreatic
Parathyroid gland
Pituitary gland
Leukemia mononuclear
Pars distalis, adenoma
Parsdistalis,carcinoma
Pars distalis, leukemia mononuclear
Thyroid gland
Gcell, adenoma
C-cell, carcinoma
Follicular cell, adenocarcinoma
Follicular cell, adenoma
1
1
3
2
28
7
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
55
55
9
55
8
.
+
+
+
+
,
M
-i-
-
1
.
.
-
+
a
+
+
+
X
1
28
22
54
1
21
1
2
54
3
1
1
1
GENER-41 ROM SYSTEMNone
GENITAL SYSTEM
Clitoral gland
Adenoma
Leukemia mononuclear
Ovary
Granulosa cell tumor malignant
Leukemia mononuclear
Luteoma
Uterus
Leiomyasarcoma
Leukemia mononuclear
Polyp stromal
Bilateral, polyp stromal
Endometrinm, adenoearcinoma
Endometrium, sarcoma stromal
Vagina
M
+
Hydro+quinone, NTP TR 366
+
+
M
+
+
Ts
%
'
.
144
24
3
2
29
1
3
1
55
1
2
5
1
1
1
1
TABLE B2* INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS : LOW DOSE
(Continued)
WEEKS ON
0 0 0 0 0 0 0 0 0 0
STUDY
CARCASS
2D
HEMATOPMETic SYSTEM
Blood
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lymph node
Mediastiaal, leukemia mononuclear
Pancreatic, leukemia mononuclear Lymph node, mandibular
Leukemia mononuclear
5
4
6
4
7
0
7
1
8
0
8
3
8
5
9
0
9
0
9
0
9
1
3
5
0
5
4
5
4
4
8
5
6
5
4
4
8
4
7
5
8
3
-I-
+
f
+
+
+
+
A-
+
+
+
+
.
.
R.
+
11
+
+
M
+
Lymph node, mesenteric
+
+
+
+
.
Spleen
-!-
+
+
k
-i-
+
bt
+
+
+
R
+
. .
+
+
+
+
Leukemia mononuclear
~
Leukemia mononuclear
Thymus
Leukemia mononuclear
`
INTEGUMENTARY SYSTEM
Mammary gland
.Adenoma
Fibroadenoma
Skin
Basal cell adenoma
Kezatoacanthoma
Subcutaneous tissue, leukemia
mononuclear
MUSCULOSKELETAL SYSTEM
Bone
Cartilage, adenocarcinoma, extension,
metastatic, thyroid gland
Skeletal muscle
Levkemia mononuclear
NERVOUS SYSTEM
Brain
Astrocytomamalignant
Leukemia mononuclear
Meninges, leukemia mononuclear
Spinal cord
Leukemia mononuclear
11Seniages, leukemia mononuclear
RESPIRATORY SYSTEM
Lung
Alveolar/bronchiolar carcinoma
Leukemia mononuclear
Nose
Leukemia mononnclear
Trachea
+
X
+
+
+
Y- S
EM
Leukemia mononuclear
Urinary bladder
+
i-
+
+
+
R
,
f
+
.
t
+
+
X
+
R
+
%
+
+
+
+
+
i-
+
%
.
R
iX
+
+
+
%
+
%
+
X
.
%
+
9
4
9
4
9
5
9
6
9
6
9
6
9
6
0
0
0
0
0
0
0
2
0
2
0
2
1
5
2
5
7
4
1
4
5
5
7
3
3
3
3
2
5
4
9
4
2
2
2
3
1
3
4
3
0
4
i-
i-
+
X
+
X
+
R
f
+
+
+
+
X
+
R
+
+
¢
R
t
+
+
X
%
.
+
¢
+
.,
a
+
+
+
X
+
R
+
+
+
g
%
+
R
g
ig
R
R
%
R
t
X
X
+
R
+
+
+
+
+
+
+
-h
+
+
.
X
+
+
i-
+
+
i~
+
t-
+
+
i-
t
i-
+
-i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
t
r
+
+
+
+
i-
t
+
+
+
4
+
+
+
+
+
+
+
X
+
g
i-
+
+
+
+
+
+
%
+
g
+
+
+
+
.
t
+
+
+
t
+.
+
t
+
%
F
+
R
+
R
+
R
+
R
+
+
R
+
+
R :
+
+
+
+
+
+
+
X
+
+
R
+
t
+
X
+
+
+
X
+
R
+
+
+
+
+
X
k
R
+
X
X
+
S-
+
+
%
+
+
X
+
.
+
+
.+ - +
+
+
+
i-
i-
+
+
.
+
+
i-
+
+
+
-+
+
+
+
+
-
R
.
+
+
R
X
+
X
X
+
+
+
+
+
t
S
+
X
+
+
+
.
X
+
+
+
g
+
X
+
1 1 i1
9
4
+
X
SPECIAL SENSES SYSTEM
Eye
Harderian gland
Zymbal gland
Kidney
+
+
%
t
+
X
0 0 0 0 0 0 0 0 1 1
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
1-
+
R
+
g
+
R
+
t
+
+
R
+
+
t
+
,
t-
+
+
+
.
+
+
+
i-
X
i-
$
+
i-
+
+
+
.
t
+
+
+
+
+
+
+
+
+
+
+
+
i-
4
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
X
R
-F
t
+
+
+
+
.
f
+
+
+
i~
+
+
+
+
+
I-
+
+
+
+
t
X
+
+
+
145
+
X
+
+
%
X
+
+
X
-i-
+
+
X
+
+
R
+
%
+
+
Fiydroquinone, NTP TR 366
TABLE B2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS: LOW DOSE
(Continued)
WEEK
N
STUDY v
CARCASS
ID
~t.`1C3A'PO~~TE
Blood
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lymph node
"
Yfediastinal, leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, :nandibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
1
0
3
1
0
3
1
0
4
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
Y
0
5
1
0
5
1
0
5
1
0
5
1 1
0
4
5
5
1
0
5
1
0
5
Y
0
8
L
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
9
3
3
1
5
2
7
2
0
3
1
1
1
2
2
1
3
2
5
1
5
2
5
3
4
2
4
3
6
4
0
2
3
1
4
1
4
2
4
1
5
1
6
1
6
2
6
3
7
1
+
+
+
+
+
+
+
+
+
+
+
+
Spleen
Leukemia mononnclear
+
+
-F
Thymns
Leukemia mononuclear
+
a-
+
Mammary gland
Adenoma
Fibioadenoma
Skin
Basal call adenoma
Karatoacanthoma
Subcutaneous tissue, leukemia
mononuclear
+
+
+
X
+
X
+
.
.
.
.
. .
_
+
+
+
X
M
+
+
+
+
+
+
+
7C
+
f
+
+
+
M, M
M
+
X
+
+
+
+
%
+
t
.
'
+
+
R
x
,
,.+
+
R
+
.
+
+
+
t
+
7K
X
+
Lung
tllveolar/bronchiolar carcinoma
Leukemia mononuclear
Nose
Leukemia mononuclear
Trachea
-1-
+
+
M
+
+
+
+
.. . .+
+
R
R . .X
'
+
+
+
.
.
.
IFES
+
-
+
Astrocytoma malignant
Leukemia mononuclear
Meninges, leukemia mononuclear
Spinalcord
Leukemia mononuclear
Meninges, leukemia mononuclear
+
Ivi
i
Brain
+
.
/ +
Bone
Cartilage, adenocarcinoma, extension,
metastatic, thyroid gland
Skeletal muscle
Leukemia mononuclear
'
. .
+
+
+
+
+
+
+
+
+
i-
+
+
+
+
+
.
.
SPECIAL SENSES
Eye
Harderian gland
Zymbal gland
Kidney
Leukemia mononuclear
Urinary bladder
.
'
Hydroqtxinone, N"rP Tft 366
+
+
+
+
.
146
+
+
+
+
+
.
+
+
.
+
+
+
+
+
+
+
+
+
LE B2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS: LOW DOSE
(Continued)
WEEKS
STUDY
rr
CARCASS
ID
i
i
a
i
i
5
5
5
5
5
o 0 o a o
TOTAL :
TISSUES
TUMORS
~5-33-~S
8
9
9
0
I
2
1
2
1
r
Blood
emia mo¢onuclear
Bone marrow
Leukemia mononuclear
Lymph node
Mediastinal, leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, mandibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
Splee
Leukemia mononuclear
Thy is
Leukemia mononuclear
Mammary gland
Adenoma,
oadeaoma
Skin
Basal cell adenoma
toacanthoma
Subcutaneous tissue, leukemia
mononuclear
UL S
E AL
10
8
28
7
28
+
+
+
+
26
5
28
8
55
+
27
6
.
+
+
t
+
R
+
55
2
22
30
1
1
%
.
3
Y TEM
28
Bone
Cartilage; adenocarcinoma, extension,
;astatic, thyroid gland
Skeletal muscle
Leukemia mononuclear
1
2
1
NERVOUS SYSTEM
Brain
icytoma malignant
Leukemia mononuclear
nges, leukemia mononuclear
Spinal cord
Leukemia moaonuclear
nges, leukemia mononuclear
28
2
3
1
.
7
+
R
Lung
Alveolarlbronchiolarcarcinoma
Leukemia mononuclear
Nose
Leukemia mononuclear
29
1
6
28
3
28
Trachea
SPECIAL SENSES SYSTEM
Eye
Harderian gland
Zymbal gland
nn
Kidney
a
Leukemia mononuclear
Urinary bladder
'
1
1
+
+
R
+
+
+
55
10
27
147
Hyclroquirxone, NTP TI$ 366
THE TWO-YEAR
TABLE B2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS IN
GAVPeGE STUDY OF IiI'I)ROQLTIN(BNE : HIGH DOSE
STUDY
CARCASS
ID
Esupyagns
Y
~
,$
6
1
8
5
0
4
8
5
5
3
+
+
+
+
+
+
5
6
6
1
2
7
5
3
5
9
5
1
5
8
3
+
+
+
+
+
+
+
+
+
+
+
+
+ +
+. +
+
+
+
+
+
9
4
+
+
.
3
5
5
6
5
2
1
1
8
6
6
+
+
+
+
+
+
+
+
i+
+
+
+
+
+
+
+
+
+
+
A
+
+
+
+
A
+
.
+
+
M
+ .
+ +
+
.+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
4
5
6
6
1
+
+
+
-F
+
+
+
2
+
+
+
+
+
2
5
+
. +.
+
4
+
+
+
4
.
+
+
4
+
i-
+
3
+
+
2
1
A
+
3
+
2
A
1
+
1
+
2
+
+
+
t-
+. +. t
±
+
+
+
+
s+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
t
+
+
+
+
+
.
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
-h
+
+
+
A
+
A
+
+
+
+
+
+
i
+
+
+
+
+
+
-h
+
+
+
+
A
+
+
A
+
A
+
+
+
+
+
R
+
+
+
+
%
+
7C
++
+
X
+
R
+
X
+
X
+
+
R
+
R
+
+
X
+
X
+
3C
+
+
X
+
X
+
%
+
+
R
+
R
+
a%
+
-.F
+
R
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
++
+
+
+
+
+
+
+
+
+
+
+
+
-1 -
+
+
+
+
+
i-
+
+
+
+
t
+
A
A
+
+
+
+
+
+
+
+
+
+
+
+
R
+
+
R
+
A
+
+
+
+
+
. X
+
x+
+
R
+
X
+
X
+
+
+
+
+
i-
A
+
+
+
+
.+
.
+
+
+
.
+
M. M
+
+
+
+
+
-F
+
+
+
+
+
+
+
+
+
+
+ . +
A
+
+
+
+
+
.
+
+
++ ++
+
+
+
+
+
i-
+
+
+
-t-
_
+
+
+
+
+
+
+
+
++
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
-1-
+
+
+
+
+ +
+ _ +
+
+
.
+
+
+
+
+
+
+
+
+
+ +
. . .
+
+
+
+
+
+
+
+
+
+
X
+
R
.
.
X
+
X
+
M
+
X
+
R
.
+
+
X
+
R
X
+
R
+
X
+
R
+
X
+
%
+
X
+
+
%
+
+
+
%
+
+
+
+
+
+
+
+
+
+
+
R
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
+
+
+
+
+
+
+
+
Arf
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
R
+
i~
+
A
+
+
+
+
+
+
+
+
X
+
.
+
+
+
+
I
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
M
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
A
R
+
+
+
+
+
X
Vagina
Squamous cell carcinoma
Hyciroquinone, NTP TR 366
2
+
None
~
2
+
.
.
1
+
-
Adrenal gland
1
Adrenal gland, cortex
Adenoma
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochromocytoma malignant
PheochromocyY.oma benign
Islets, pancreatic
Leukemia mononuclear
Parathyroid gland
Leukemia mononuclear
Pituitary gland
Leukemia mononuclear
Meningioma malignant, metastatic
Parsdistaiis,adenoma
Pars distalis, leukemia mononuclear
Thyroid gland
Leukemia mononuclear
C-cell, adenoma
,
C-cell, carcinoma
1
8
+
+
+
F'
+
+
+
+
7
4
A
.
Heart
Leukemia mononuclear
9
4
+
~ +
Intestine large
Iatestine large, cecum
Leukemia mononuclear
Intestine large, colon
.
Leukemia mononuclear
.
.
Intestine large, rectum
Leukemia mononuclear
Intestine small '
Intestine small, duodenum
Leukemia mononuclear
Intestine small, ileum
Leukemia mononuclear
Sarcoma
.
Intestine small, jejunum
Cystadencearcinoma
Leukemia mononuclear
Sarcoma
Liver
Leukemia monoauclear
.
Mesentery
Leukemia mononuclear
malignant,
extension,
Pheochromocytoma
metasfatic, adrenal gland
Pancreas
Leukemia mononuclear
Salivary glands
Leukemia mononuclear
Stomach
Stomach, forestomach
.
Leukemia mononuclear
Stomach, glandular
mononuclear
Leukemia
Tooth
Pulp, leukemia mononuclear
Clitoralglaad
Adenoma
Leukemia mononuclear
Ovary
Leukemia mononuclear
Oviduct
Leukemia mononuclear
Uterus
Leukemia mononuclear
Polyp stromal
1 1 1 1 1 1 -1 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 09 09 10 01
4 6 7 8 8 8 9 9 9 94 94 94 94 96 7 9 0 0
WEEKS N
148
M
f
+
+
M
+
+
.
+
X
+
+
+
.
+
+
+¢+++++
x
X+
+
+
+
+
t
+
.
+
+
+
+
+
+
+
A
Y
+
+
+
+
+
+
+
+
X
+
+
+
+
+
.
TABLE B2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS:' HIGH DOSE
(Continued)
WEEKS
.STUDY
N
-
.
CARCASS
ID
Esophagns
Intestine large
Intestine large, cecum
Leukemia mononuclear
11
0
0
5 5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
I' l
0
0
5
5
1 . 1 . 1
0
0
0
5
5
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
4
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
-B--T
9
0
3 3
7
1
1
7
2
1
7
4
3
7
4
4
7
6
3
7
7
2
7
7
3
7
7
4
6
7
3
6
9
1
6
9
2
7
0
2
7
3
2
7
3
3
7
3
4
-7
4
1
7
4
2
6
2
7- 7
7
8
1
3
7
8
4
6
7
2
6
7
2
+
+
+
+
.+
+
+
+
.
Intestine large, colon
Leukemia mononuclear
Intestine large, rectum
Leukemia mononuclear
Intestine small
Intestine small, duodenum
Leukemia mononuclear
Intestins small, ileum
Leukemia mononuclear
.
.,
.
.
Sarcoma
Intestine small, jejunum
CysCadeaocarciaoma
Leukemia mononuclear
Sarcoma
Liver
Leukemia mononuclearMesentery
Leukemia mononuclear
PheocLromocytoma malignant, extension,
metastatic, adrenal gland
Pancreas
.
.
+
+
+
i~
+
+
-t
-c.
+
+
+
+
+
+
+
+
+
i~
+
,-
i+
+
+
+
+
+
'+
+
t
+
+
+
-it
+
+
+
t
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
.
+
+
+
+
+
+ . +
i-
+
-h
+
+
+
+
+
+
+
+` +
+
+
+
.
+
+
-F
.
+
+
+
+
t
+
+
+
+
+
+
+
-F
+
+
+
-t+
t
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t-
i+
+
+
+
+
+
+
+
+
+
+
¢
+
+
+
+
+
+
+
+
+
+
..
+
.
+
^
.. .
+ .+
+
+
+
+
+
+
+
+
-F
+
%
+
t
+
+
+
+
+
+
+
+
+
+
+
3-
+
+
+
+
+
+
+
+
X
+
.
+
+
-h
i-
+
+
+
+
+
+
+
i-
+
+
+
.
+
+
t
R
.
Leukemia mononuclear
Salivary glands
Leukemia mononuclear
Stomach
Stomach, forestomach
Leukemia mononuclear
Stomach, glandular
Leukemia monanuclear
Tooth
Pulp, leukemia mononuclear
CARDIOVASCULAR SYSTEM
Heart'
Leukemia mononuclear
ENDOCRINE SYSTEM
Adrenal gland
Adrenal gland, cortex
Adenoma
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochroacocytoma malignant
Pheochromocytoma benign
Islets, pancreatic
Leukemia mononuclear
Parathyroid gland
Leukemia mononuclear
Pituitary gland
Leukemia mononuclear
1Lieningioma malignant, metastatic
Parsdistalis,adenoma
Pars distalis, leukemia mononuclear
Thyroid gland
Leukemia mononuclear
C-cell, adenoma
C-cell, carcinoma
+
+
+
+
+
.
+
+
+
+
+
+
+
+
R
NL
+
+
+
+
+
.
+
+
+
+
a+
+
+
+
-
X
%
+
+
+
+
+
+
+
+
+
+
+
+
X
-'r
X
+
+
X
+
X
+
t-
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
a
+
+
+
+
t
+
X
f
+
+
+
+
+
.+
+
+
+
+
+
+
+
+
+
+
+
-h
+
+
i+
+
%
+
+
+
+
+
+
X
+
r
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
,-
+
+
+
+
+
+
+
X
+
I{
+
+
%
%
+
+
+
+.
+
+
+
+
+
+
+
+
+
+
+
A
+
+
+
+
+
+
+
+
+
+
+
-e+
+
+
.
+
S
+
X
+
+
+
+
i-
+
+
+
+. +
i-
+
+
+
+
+
+
+
t
X
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
i+
+
+
+
+
+
+
.
+
+
a-
+
+
+
+
+
+
+
+
+
+
X
+
X
+
+
+
+
+
.
X
+
X
+
+
+
+
. ..
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
%
+
R
+
+
X
+
+
+
+
+
+. +
X
+
X
X
+
.
+
+
X
R
+
R
+
-
X
X
X
+
+
+
R
+
+
+
X
X
R
+
+
+
+
+
+
+
+
.+
'+
+
+
%
+
X
R
t
X
+
+
t
+
+
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
X
+
%
+
+
+
R
+
+
+
X
+
+
+
R
+
+
X
%
+
X
+
R
GENERAL BODY SYSTEM
None
GENITAL SYSTEM
Clitoral gland
Adenoma
Leukemia mononuclear
Ovary
Leukemia mononuclear
Oviduct
Leukemia mononuclear
Uterus
Leukemia mononuclear
Polyp stromal
Vagina
Sqnamaus cell carcinoma
'
I
~
~
+
+
+
+
r
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
X
+
+
+
+
X
X
X
+
+
X
-h
+
%
+
X
¢
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
X
X
149
+
X
X
+
+
+
+
%
+
+
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
+
+
+
+
i-
X
X
I
I
I
Hydroquinone,-1VTP TR 366
TABLE B2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE HATS: HIGH
(Continued)
WEEKS ON
STUDY
CARCASS
ID
Esophagus
2ntestine Iarge
Intestine large,cecum
Leukemia mononuclear
Intestine large, colon
Leukemia mononuclear
rectum
Intestine large,
Leukemia mononuclear
Intestine small
Intestine small,duodenum
Leukemia mononuclear
Intestine small, ileum
Leukemia mononuclear
Sarcoma
Intestine small, jejunum
Cystadencearcinoma
Leukemia mononuclear
Sarcoma
Liver
Leukemia mononuclear
Mesentery
Leukemia mononuclear
Pheochromocytoma malignant,
exCensioa,metastatic, adrenal gland
Pancreas
Leukemia mononuclear
Salivary glands
Leukemia mononuclear
Stomach
Stomach, Forestomach
Leukemia mononuclear
Stomach, glandular
Leukemia mononuclear
Tooth
Pulp, leukemia mononuclear
CARDIOVASCULAR SYSTEM
Heart
Leukemia mononuclear
ENDOCRINE
Adrenal gland
Adrenal gland, cortex
Adenoma
Leukemia mononuclear
Adrenal gland, medulla
Leukemia mononuclear
Pheochromacytoma malignant
Phaochmmocytoma benign
Islets, pancreatic
Leukemia mononuclear
Parathyroid gland
Leukemia mononuclear
Pituitary gland
Leukemia mononuclear
Meningioma malignant, metastatic
Pass distalis, adenoma
Para distal* leukemia mononuclear
Thyroid gland
Leukemia mononuclear
C-cell, adenoma
C-cell, carcinoma
r
i
0
5
i
0
5
i
0
5
SE
x
0
5
0
5
TOTAL:
TISSUES
TUMORS
-'~'7---'7--'f0 3
6
8 8
1
1
1
1
2
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ . -r
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-h
+
+
+
+
+
+ .
55
55
53 ,
.
.
54
.
,
+
+
+
+
+
+
+
+
+
M
-
-
51
1
55
22
16
+
x
+
+
+
+
+
55
+
+
+
55
+
+
+
+
+
+
+
+
54
54
.
+
+
+
.
,
-
54
.
5
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
+
Q
55
+
+
+
+
.
54
+
+
+
+
+
54
R
%
+
+
+
+
lg
L
55
%
X
.
P.
+
55
13
-
55
55
1
14
54
12
_
GEN
None
GENITAL S
Clitoral gland
Adenoma
Leukemia mononuclear
Ovary
Leukemia mononuclear
Oviduct
Leukemia mononuclear
Uterus
Leukemia mononuclear
Polyp stromal
Vagina
Sqvamous cell carcinoma
'
53 - .
53
. '
.
+
X
51
.
-tR
+
+
-i-
+
+
+
+
+
+
+
+
%
X
I-iyds'oq111Y1Orle, NT'$''T`R 366
+
+
2
52
.
55
+
55
X
+
1
150: .
TABLE B2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS: HIGH DOSE
(Continued)
v~rEEx oN
- --
STUDY
CARCASS
ID
M
Blood
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lymph node
Asillary, leukemia mononuclear
Deep cervical, leukemia mononuclear
InguYnal, leukemia mononuclear
Lumbar, leukemia mononuclear
Mediastinal leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, mandibular
Leukemia mononuclear
Lymph node, mesenteric
Leukemia mononuclear
Spleen
Leukemia mononuclear
Thymus
Leukemia mononuclear
INTEGUMENTARY SYSTEM
Mammary gland
Adsncearcinoma
Fibroadeoama
Fibroadenoma, multiple
Leukemia mononuclear
Skin
Keratoacanthoma
Papilloana squamous
SubcuCaaeoua tissue, leukemia
mononuclear
Subcutaneous tissue, sarcoma
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1
4
9
6
6
7
1
8
4
8
5
8
6
8
6
9
1
9
2
9
4
9
4
9
4
9
4
9
6
9
7
9
9
0
0
0
0
0
1
0
1
1
1 1 1
0
2
0
2
0
3
0
5
0
5
16
8
5
7
0
4
7
8
5
7
5
3
7
7
5
7
3
5
6
9
5
7
1
5
6
8
3
6
9
4
6
7
4
6
8
2
7
4
5
7
5
2
7
6
4
6
6
4
7
1
4
6
6
3
7
5
1
7
2
2
7
1
3
7
1
2
6
8
1
6
6
1
6
6
2
+
+
X
+
k
+
X
+
7C.
+
i-
.
+
+
. X
+
R
+
R
+
R
+
+
+
+
+
+
+
+
+
X
+
+
+
X
+
+
+
-F
+
+
. i-
.
+
+
M
+
+
+
+
+
+
+
aB
+
+
X
.
R
+
+
+
+
+
+
X
+
%
+
R
+
X
+
+
+
+
+
+
+
+
i-
i-
+
+
X
+
R
S
7{
R
X
+
A
+
R
+
7C
+
X
,
4
+
+
+
aC
+
+
X
+
+
%
+
R
+
X
+
:C
+
R
+
%
+
X
+
7C
+
X
+
+
+
+
R
R
+
+
+
+
+
+
+
+
+
+
A
.
X
+
Leukemia mononuclear
Meninges, leukemia mononuclear
Meninges, meaingioma malignant
Spinal cord
Meninges, leukemia mononuclear
RESPIRATORY S STEM
Lung
Alveolar/bronchiolar carcinoma
Carcinoma, metastatie, thyroid gland
Leukemia mononuclear
Pheochromocytoma malignant,
metasCatie, adrenal gland
Nose
Leukemia mononuclear
Trachea
Leukemia mononuclear
+
+
+
+
+
+
f
+ +
% ,
+ +
+
+
t
+
+
X
X
+
'
+
X
URINARY SYSTEM
Kidney
Leukemia motonuclear
Urinary bladder
Leukemia mononuclear
+
+
+
A
+
.
+
+
R
-i-
.R
+ +
+
+
+
+
X
+
+
+
+
+
+
+
+
+
+
i-
-t-
7C
X
+
+
+
+
R
+
+
R
+
t
+
X
+
+
X
%
+
+
t
It
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
¢
+
+
+
+
+
+
+
+
+
+
+
-F
+
M
+
+
+
X
,
+
+
+
+
-
+
+
7C M +
+
+
+
k
+
R
151
X
+
R
+
X
+
X
.
+
1
1
%
+
R
+
%
+
X
+
R
+ riA
X.
+ +
7C
+ +
A
+ +
A
+
X
+
X
+
R
t
+
R
+
S
t
X
.
+
+
o-
+
+
+
+
+
t
+
+
+
+
+
+
+
+
.
Yf
+
+
+
+
R
+
+
+
+
%
IdY
+
-t-
+
+
i-
+
+
+
+
.+
+
+
+
+
+
+
+
+
X
%
+
+
X
%
+
+
+
+
+
+
X
i-
-F
+
X
+
+
+
+
R
+
+
+
+
%
+
f +
+
X
+
X
+
+
R
X
+
IC
+
%
+
t
R
+
R
+
%
+
R
+
R
+
R
SPECIAL SEN SES SYSTEM
Harderian gland
Zymbat gland
Carcinoma
.
%
MUSCULOSK ELETAL SYSTEM
Bone
Skeletal muscle
Leukemia mononuclear
Pheochromocytoma malignant, extension,
metastatic, adrenal gland
NERVOUS SYSTEM
Brain
+
%
X
X
+
+
1
+
X
+
+
+
X
X
+
+
+
+
+
+
R
+
R
+
+
%
t
+
+
+
+
+
+
%
.
X
X
+
+
+
R
+
A
f
+
+
+
+
+
R
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Hydroquinone, NTP TR; 366
OF FEMALE RATS: HIGH DOSE
ANIMAL TUMOR PATHOLOGY
TABLE B2. INDIVIDUAL
.
(Continued)
WEEK
STUDY
CARCASS
ID
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5=
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
0
5
9
3
0
3
1
1
2
1
4
3
4
4
6
3
7
2
7
3
7
4
7
3
9
1
9
2
0
2
3
2
3
3
3
4
4
2
4
2
6
2
7
1
8
3
8
4
7
1
7
2
+
X
+
-I'
.
Lymph node
Anllary, leukemia mononuclear
Deep cervical, leukemia mononuclear
Ingninal, leukemia mononuclear
Lumbar, leukemia mononuclear
Mediastinal, leukemia mononuclear
Panc reatic, leukemia mononuclear
Lymph node , maadibular
Leukemia monohnclear
Lymph node, mesenteric
Leukemia mononuclear
Spleen
Leukemia mononuclear
Thymus
Leukemia mononuclear
Mammary gland
Adeaocarcinoma
Fibmadeaoma
Fibroadenoma, multiple
Leukemia mononuclear
Skin
Keratoacanthoma
Papil3oma squamous
Subcutaneous tissue, leukemia
mononuclear
Subcutaneous tissue, sarcoma
-
.
. .
0
5
+
Blood
Laukemia mononnclear
Bone marrow
Leukemia mononuclear
-
0
5
..
'S'
Alveolar/bronchiolar carcinoma
Carcinoma, metastatic, thyroid gland
Leukemia mononuclear
Pheochromocytoma malignant,
metastatic , adrenal gland
.
.
-F
F
.
+
+
+
+
+
+
-F
+
+
+
+
+
+
a-
+
+
+
+
+
+
+
+
%
+
+
+
+
+
+
X
R
+
+
+
t
+
+
+
M
+
M
+
~
+
+
+
+
+
X
-F
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
K
R
~
+
+
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
.
t
t
+
+
+
+
+
+
¢
+
+
.
i'
+
.
.
+
R
.
+
+
+
+
+
+
R
+
+
x
+
+
R
+
+
X
+
.
+
+
+
+
+
+
+
+
X
+
+
+
+
+
+
+
+
~
+
+
-F
+
+
+
+
+
+
-F
.
+
. . .
+
+
+
x
+
X
+
+
+
+
+
+
+
+
+
+
+
+'
~.
X
+
-F
+
+
+
+
X
?~
x
+
+
x
X
X
~
X
+
i-
-F
+
+
+
+
t
+
+
t
+
fi
S
+
X
%
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
X
+
+
--.
+
+
+
Lung
-F
°
+
X
-I-
+
+
13raie
Leukemia mononuclear
Meninges, leukemia mononuclear
Meninges, meningioma malignant
. .
Spinal cord
Meninges, leukemia mononuclear
+
7C
-F
X
+
x
Bone
Skeletal muscle
Leukemia mononuclear
Pheochenmocytoma malignant, extension,
metastatic, adrenal gland
Nose
Leukemia mononuclear
Trachea
-f
+
X
'F
X
+
+
+
+
R
+
+
+
X
+
.
+
.
,
+
.
+
+
.
.
+
+
+
+
+
x
+
+
:C
+
Leukemia mononuclear
Eye
Harderiangland
Zymbal gland
Carcinoma
Kidney
Leukemia mononuclear
Urinary bladder
Leukemia mononuclear
Fiydroquinone, NTP TR, 366
.
+
+
+
+++
.
+
+
f
+
M
+
+
X
+
X
++
++
+
+
+
i-
+
+
+
+
+
+
+
+ ~+
+
t
+
+
+
+
X
X
+
+
+
X
X
k
+
a-
+
+
i-
i-
+
+
.
;-
-h
+
+
+
+
+
+
+
+
+
+
+
+
+
152
+
+
X
+
+
+
+
+
%
_
X
.
.
X
+
+
+
+
+
i-
-5-.
+
+
+
+
.
.
+
+
+
R
i-
a-
+
+
i-
+
+
+ +
+
+
+
+
+
+
+
X
+
+
X
+
x
+
*
.
.
+
+
'r
+
+
+
i
-h
i-
+
+
+
+
X
+
X
+
+
+
+
+
+
+
+
+
+
+
6
:
E
t
TABLE B2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF FEMALE RATS- HIGH DOSE
(Continued)
-
WEEI~S-ON ~
STUDY
1 . 1
Q
0
5
5
1
0
5
1
0
5
1
0
CARCASS
TD
7
0
T
7
3
1
7
6
2
7
8
1
E
f
+
*
+
f
+
+
+
t-
+
Slood
V
Leukemia mononuclear
Bone marrow
Leukemia mononuclear
Lymph node
' Asillary, leukemia mononuclear
Deep cervical, leukemia mononuclear
Inguinal, leukemia mononuclear
Lumbar, leukemia mononuclear
Mediastinal, leukemia mononuclear
Pancreatic, leukemia mononuclear
Lymph node, azandibular
Leukemia mononuclear .
Lymph node, mesenteric
Leukemia mononuclear
Spleen
Leukemia mononuclear
Thymus
Leukemia mononuclear
GUMENTARY SYSTEM
Mammary gland
Adenocarcinoma
Fibmadenoma
Fibroadenoma, multiple .
Leukemia mononuclear
Skin
Keratoacanthoma
Papilloma squamous
Subcutaneous tissue,leukemia
mononuclear
Subcutaneous tissue, sarcoma
MMC ULOSKELFTAL SYSTEM
Bone
Skeletal muscle
Leukemia mononuclear
Pheochmmocytoma malignant,
extension, metastatic, adrenal gland
~ 'RVOUS
Brain
Leukemia
Meninges,
Meninges,
Spinal cord
Meuinges,
SYSTEM
mononuclear
leukemia mononuclear
meningioma malignant
.
.
18
15
55
11
55
,
.
.
.
°
g
g
+
+
-t-
R
+
+
+
a-
+
t
:
~F-
_~-
+- +
+
+
$
M
+
+
+
R
+
+
+
-F
ri-
.
.
. .
,
.
.
.
. .
.
.
55
22
51
9
54
21
-F
r
+
+
+
.
a-
+
+
+
+
-~
g
55
_
q
55
55
q
+
+
lg .
,
.
+
.
52
13
54
},
-
+
.
.
.
,
-
leukemia mononuclear
RESPIRATORY SYSTEM
Lung
Alveolar/bronchiolar carcinoma
Carcinoma, metastatic, thyroid gland
Leukemia mononuclear
Phxochromocytoma malignant,
metastatic, adrenal gland
Nose
Leukemia mononuclear
Trachea
Leukemia mononuclear
TOTAL:
TISSUES
TUMORS
i-
12g
.
'
.
+
+
+
-h
,
+
+
+
+
-;
55
15
.
y
55
55
SPECrA~$
Ha rderian gland
Zymbal gland
Carcinoma
UIIN
Kidney
Leukemia mononuclear
Urinary bladder
Leukemia mononuclear
r
6
1
+
+
+
c-
,
+
+
+
+
.
55
16
51
g
153
Hydroquinone, NTPTI$ 366
TABLE s3 . ANALYSIS OF PRIMARY TUMORS IN FEMALE RATS IN THE TWO-YEAR GAVAGE STUDY
OF xYDROQtraNorrE
Adrenal Medulla : Pheochrornoeytorria
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day ofFirst Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Ccehran-Arrimitage Trend Test (d)
Fisher Exact Test (d)
Vehicle Control
25 mg/kg
50 mg/kg
2/54(4%)
4.9%
1140(3%)
722
P=0 .19fl
P=0 .230
P=0238
1/55(2%)
2 .1%
0/27(0%)
625
P=0 .b93N
P=0 .496N
4/54(7%)
11 .3%
3/32(9%) ,.
652
P=0256
P=0 .310
P=0.493N
P=0 .339
3/54(6%)
7 .3%
2/40 (5%)
722
P=0 .207
P=0260
P=0283
3/56(5%)
9 .4%
2/27(7%)
625
P=d .502
P=0.629
5/54(9%)
14 .0%
3/32(9%)
652
P=0259
P=0 .320
P=0.652N
P=0 .358
4/51(8%)
10 .1%
3/38(8%)
710
P=0 .046
P=0 .058
3/55(5%)
9 .6%
1/27(4%)
672
P=0 .637
F'=0 .546N
9/52(17%)
26 .8%
8/32(25%)
669
P=0 .066
P=0 .089
P=0 .458N
P=0 .125
2915b t53°!o)
612%
22/40(55%)
500
P=0 .377N
P=0 .121N
P=0 .Id6N
22/65(40%)
54 .9%
10/27(37%)
595
P=O.b15
P=0 .161N
22/55(40%)
55 .0%
15/32(47%)
588
P=0 .397N
P=0 :138N
P=0 .126N
P=0 .126N
29/55(53%)
61 .2%
22/40(55%)
500
P=0 .382N
P=0 .122IlI
P=0 .10&1V
23155(42%)
57 .5°l0
11/27(41%)
595
P=0 .439
P=0 .217N
22/55 (40%)
55.0%
15/32 (47%)
588
P=0 .397N
P=0 .138N
P=d .l'70N
P=0 .126N
3/55(5%)
6 .8%
1/40(3%)
646
P=0228N
P=0 .183N
P=0 .1761>T
0/65 (0%)
O .Q°r'o
0/27(0%)
P=0 .175N
P--0.123N
1155 (2%)
3 .1%
1/32(3%)
729
P=0 .371N
P=0 .312N
P=0 .122N
P=0.309N
Adrenal Medulla: PheOCI1COIllOCytOE'Yl`sk°°BeR1gYlr Complex, or Malign ant
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day ofFirst Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cachran-Armitage Trend Test (d)
Fisher Exact Test (d)
Clitoral Gland : Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Lay of First Observation
Life Table Tests (d)
Logistic Regression Tests (ci)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
Mammary Gland: Fibroadenama
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
Mammary Gland: Adenoma or Fnbroadenoana
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
'
Mammary Gland : Adenocarcinama
Overall Races 1 a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests td7
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
Hydroquinone,l<1TI' Tft 366
P=0.075
154
ANALYSIS OF PRIMARY 'TUMORS IN FEMALE RATS IN THE TWO-YEAR GAVAGE STUDY
OF HYI9ROQil%NODIE (Continued)
Vehicle Control
t
j
'
j
25 mg/kg
50 mg/kg
23/55(42%)
57.59'o
11/27(41%)
596
P=0 .496
P=0 .16bId
22/55(40%)
55 .0%
15/32(47%)
588
P=0.3391V
P=0 .100N
P=0 .126N
P=0 .091N
21154(39%)
54.?%
11/27 (41%)
492
P=0 .272
P =0 .456N
16/54(30%)
44.5'% .
13/32( 41%)
492
P=0 .300N
P=0 .126N
F=0 .422N
P=0.215Pd
24154(44%)
b0.49'0
18/39(46%)
476
P=0 .2SSN
P=0 .077P1
1'=4 .069RI
22154 (41 %)
54 .79'0
11127 (4I9'o)
492
P=0 .272
P=0.463N
16/54 (30%)
44.59'0
13/32(41%)
432
P=0 .300N.
P=0 .090N
P=0 .423N
F'=0 .O81N
Thyroid Gland: C-Cell Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
9/55(16%)
22 .2%
7/40(18%)
674
P=0 .245PT
P'=0 .172N
P=0 . 137N
3/54(6%)
1E1 .0%
2/27(7%)
700
P=0 .1&7M
P=0 .110N
6/55(9%)
13 .9%
3/32(9%)
676
P=0 .322N
P=0 .230N
P=0 .066I61
I'=0 .196N
Thyroid Gland : C-Cell Carcinoma
Overall Rates (s)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d) .
Fisher Exact Test (d)
4/55(7%)
9.49'0
3/40(8%)
647
P=0 .511N
P=0.448N
P=0 .412N
1/54(2%)
3.196
0/27 (03'0)
709
P=0 .285N
P=0 .207N
3/55(5%)
9.4%
3/32(9%)
?23
P=0 .606N
P'=0 .536Id
F=0 .L87IV
P=0.500N
Thyroid Gland : C-Cell Adenoma or Carcinoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
13/55 (24%)
29 .9°l0
10/40(25%)
64?
P=0 .244N
P=fD .153N
P=0 .I16IV
4/54(7%)
12 .8%
2/27(7%)
700
P=0 .O8SN
P=0 .03$N
8/55(15%)
22.SR'o
6/32(19%)
676
P=0 .320Pd
P=0 .205N
P=O .OflSN
P=0 .166N
Mammary Gland: Adenoma, Filbroadenorna, or Adenocarcieaoma
Overall Rates (a)
30/55(55%)
Adjusted Rates (b)
62 .1%
Terminal Rates (c)
22140 (55%) .
Day of First Observation
500
Life Table Tests (d)
P=0 .326N
Logistic Regression Tests (d)
&'=Q.097N
Cochran-Armitage'Prend Test (c3)
P=0.075IV
Fisher Exact Test (d)
Pituitary ~°xt$Y1d/P$Y'9 Distalis : Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Teat (d)
Fisher Exact Test (d)
23/54(43%)
50 .4%
17/39 (44%)
476
P=0 .295iV
P=0.1(38Pd
P=0 .098N
Pituitary Glfl7dfUP3H'8 Distalis : Adenoma or Carcinoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
155
Hyda°oquinone, IVTP TR, 366
RATS IN THE TWO-YEAR CaAVAGE STUDY
TABLE B3o ANALYSIS OF PRIMARY TUMORS IN FEMALE
OF Yi'Y'I3IZOQl1INONE (Continued)
Uterus: atroaiad Polyp
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
,
Day of First Observation
Life Table Tests (cl)
Logistic Regression Tests (d)
Cochran-Armatage Trend Test (d)
Fisher Exact Test (d)
Vehicle Control
25 mglfsg
50 mg/kg
12/55(22%)
27 .4%
9140(23%)
647
F'=0.407N
P=02'd1N
P°-0.260N
6155(11%)
15 .9%
2/27(7%)
626
Pr0.2'10N
P=0.414N
9/55(16%)
23 .3%
5/32(16%)
597
P=0 .479N
P=0 .331N
P=0 .098N
P=0.314Id ,
15/55(27%)
37.9%
6/27(22%)
576,
P=0 .048
F'=0 .129
22/55(40%)
49 .6%
11132 (34%) ,
492
P=0.003
P=0 .006
P=0 .224
P=0 .005
Hematopoaetnc System : Mononuclear Leukemia
9l55 (16%a)
Overall Rates (a)
49.4%
Adjusted Rates (b)
4/40(10%)
Terminal Rates (c) :
853
Day of First Observation
P =0 .003
Life Table Tests (d)
P=(D .d304
Logistic Regression Tests (d)
P=0 .a04
Cochraaa-Armif.age Trend Test (d)
Fisher Exact Test (d)
(a) Number of tumor-bearing animals/number of animals examined at the site ,
for interctirrent mortality
(b) Kaplan-MeSer estimated tumor incidences at the end of the study after adjusting
terminal
kill
tumor
incidence
at
(c) Observed
trend test. Beneath the dosed group incidence are
(d) Beneath the vehicle control incidence are the P values associated with the and the vehicle controls. The life table analysis
that
dosed
group
between
the P values corresponding to paiiwise comparisons
indirectly) the cause off death . The logistic regresregards tumors in animals dying prior to terminal kill as being (directly or exact tests compare directly the overall incidence
and
Fisher
Cochran-Armitage
as
nonfatal
.
The
regards
these
lesions
sion test
rates. A negative trend or lower incidence in a dosed group is indicated by (?d) .
Hydroquinone, IVTP TR 366.
156
TABLE B4a . HISTORICAL INCIDENCE OF LEUKEMIA IN FEMALE F344/N RATS (a)
Incidence in Controls
Study
Historical Incidence for All Water Gavage Vehicle Controls
Iodinated glycerol (b)
Malonaidehyde, sodium salt (c)
Chtorpheniramine maleate (c)
°fetieakis(hydroaymetlayl)phosphanium chloride (c) .
Tetrakis(hydrosymethyl)phosp6onium sulfate (c)
Methyl carbamate (d)
1S/50
515(}
11f50
4150
23/49
1TI50
75/299 (25.1'Yo)
14 .90%
TOTAL
SD (e)
Range (f)
High
Low
23/49
4/5U
Overall Historical Incidence foe Untreated Controls
TOTAL
SD (e)
35304,983 (flS.3%)
6.6&~'0
Range (f)
High
Tow
15/49
3/50
(a) Data as of April 29,1987, for studies of at least 104 weeks
(b) Study performed at EG&G Mason Research Institute
(c) Study performed at Sattelie Columbus Laboratories
(d) Study performed at 1lgicrobiological Associates
(e) Standard deviation
(f) Range and SD are presented for groups of 35 or more animals.
157
I-¬ydroquznonee NTP TR,`366
'
FEMALE F344/N
TABLE B4b . HISTORICAL INCIDENCE OF THYROID GLAND C-CELL TUMORS IN
RATS (a)
Steady
Adenoma
Incidence in Controls
Carcinoma
Adenoma or
Carcinoma
Historical Incidence for All Water Gavage Vehicle Controls
0146
9150
4/47
6/5m
2f49
2150
iodinated glycerol (b)
113alomaldehyds, sodium salt (c)
Ch9orpheniramine maleate (c)
Tetrakis(hydrosymethyI)phosphonium chloride (c)
Tetrakis(hydrogymethyl)phosphonium sulfate (e)
Methyl carbamete (d)
TOTAL
SD (e)
2146
0150
0/47
1150
3149
d/50
23l292 (7 .9%)
6 .50%
6/292(2 .1%)
2 .63`3'0
9/50
0/46
3149
0150
Range (f)
High
Low
2/46
915fl
4/47
?/50
5/49
2/b0
29/292 (9 .99'0) ;
5 .48%
9150
2150
Overall Historical Incidence for Untreated Controls
TOTAL
5D (e)
Range (f)
High
Low
155f1,938 (8 .0%)
7 .21%a
17/50
0/50
(a) Data as of April 29,1987, for studies of at least 104 weeks
(b) Study performed at EG&G Mason Research Institute
(c) Study performed at Battelle Columbus Laboratories
(ci) Study performed at Microbiological Associates
(e) Standard deviation
(fl Range and SD are presented for groups of 35 or more animals.
Hydroquinone, IV'PP TR 366
159
66/1,938 (3 .4%)
2 .753'0
5/50
0J50
218/1,938 (11 .2%)
7 .20%
19/50
0/50
TABLE B5 . SUMMARY OF 'THE INCIDENCE OF NONNEOPLASTIC LESIONS IN FEMALE RATS IN THE
TWO-YEAR GAVAC*E STUDY OF HYDROQUINONE
Vehicle Control
Animals initially in study
Animals removed
Animals examined histopatlaologically
ALIMENTARY SYSTEM
Intestine small, duodenum
Erosion
Inflammation, suppuiative
T .iver.
Basophilic foeus
Ctear cell focus
Congestion
Cytomegaly
Degeneration, cystic
Eosinophilic focus
Fatty change
Fibrosis, focal
Focal cellular change
FIematopoietic cell proliferation
Hemorrhage
iepatodiaphragmatic nodule
Hype rplasis, focal
Inflammation, chronic
Inflammation, granuTomatous
Mineralization
Mixed cell focus
Necrosis, coagulative
Arteriole, inflammation, proliferative
Bile duct, hyperplasia
CenCrilobular, atrophy
Sinusoid, dilatation
Mesentery
Pigmentation, hemosiderin
Arteriole, degeneration, hyaline
Arteriole, inflammation, chronic
Fat, hemorrhage
Fat, inflammation, acute
Fat, inflammation, chronic
Fat, inflammation, granulamatous
Fat, mineralization
Fat, necrosis
Fat, pigmentation, hemosiderin
Pancreas
Atrophy
Focal cellular change
Inflammation, chronic
Duct, fibrosis
Duct, necrosis, coagulative
Pharynx
Hyperkeratosis
Inflammation, chronic
Salivary glands
Atrophy, focal
Cytoplasmic alteration
Arteriole, inflammation, proliferative
Duct, ectasia
Duct, inflammation, chronic
Duct, metaplasia, squamous
Low Dose
High Dose
6s
65
56
65
65
55
65
65
65
(55)
(28)
(55)
1
1
(55)
30
5
1
2
(5b)
30
5
1
1
1
1
9
(b5~'~)
(9%)
(2%)
(29'0)
(2%)
(2~'0)
(16%)
2 (4%)
9 (469'0)
39 (71%)
1 (2%)
4 (7%)
4 (7~/'0)
41 (75%a)
4 (7%)
3 (63'0)
(7)
1 (14%a)
(55)
38
fs
1
2
1
2
10
(69%)
(11%)
(2%)
(4~3'0)
(2%)
(4°l0)
(18%)
I
2
1
t0
(2%)
(4%)
(2°ln)
(I8%)
30 (553°0),
3 (5%)
1 (2%)
3 (5%)
36 (65%)
3 (5%)
I (2%)
(13)
1 (8%)
1 (8%)
6 (46R'o)
1 (8%)
3 (43%)
(55)
2 (4%)
1 (2°lo)
P (23'0)
(55)
1 (2%)
3 (5%)
13 (24%)
5 (99'0)
159
a cs%>
5 (38%)
(28)
L (4%)
1
(1)
1
1
(26)
1
(2%)
(24'0)
(55%)
(99b)
(29'0) ,
(4%)
9
2
1
1
(16%)
(4%)
(2%)
(2%)
11
1
31
1
1
2
4
I
41
10
3
(16)
I
(205'0)
(2%)
(56%)
(2%)
(2g'o)
(4%)
(9%)
(29'0)
(75%)_
(18~''n)
(5%)
(63'0)
2 (13%)
1 (6%'0)
5 (31R'o)
7 (44%)
1 (64'0)
(55)
I (2%)
(4%d)
(100Wo)
(100%)
(4%)
i (4%)
I (43'0)
3 (1`L~Y'o)
(55)
3 (5%)
2 t4%?
1 (2%)
6 (11%)
12 (22~'a)
Hyclroquinmne, NTP TFd, 366
OF NoNrrEoPLASTIc LESIONS Ix FEMALE RATS IN THE
TABLE Bs. SUMMARY OF THE INCIDENCE
taAB7AH3E STUDY OF H'dr3IiOQUIF70P1E (Continued)
TWO-YEAR
.
.
.
.
ALIMENTARY SYSTEM (Continued)
Stomach, forestomach
Acanthosis
H3'Perkeratosis .
Hyperplasia, papillary
Inflammation, acute
Inflammation, chronic
Ulcer
Stomach, glandular
Inflammation, acute
CARDIOVASCULAR SYSTEM
Heart
~
fp:ab t'diamy~o~ypathy
.
Vehicle Control
(55)
Y 62%3
1 (2~3'0)
1 (2%)
1 (2%)
3 (5%)
(b6)
(55)
46 (84g'o) .
High Dose
Low Dose
(64)
2 (4%a)
2 (4%)
(28)
2 (7%)
2 (7%)
g (4%)
1 (2%) .
2 (7%)
(28)
fl (4%)
(54)
(28)
20 (71°l0)
(55)
42y (/ 7ry6~y%)
.tBOny c h ronic
114rLUmy
nflammation,
Atrium, iI1L1a$n$Tl~
A
Atrium, thrombus
ENDOCRINE SYSTEM
Adrenal gland, cortex
Accessory adrenal cortical nodule
Angiectasis
Atrophy
Cyst
I2egeneratian,fatty,focal
Degeneration, focal
Fiematopoietic cell proliferation
Hyperplasia
Hypertrophy
Hypertrophy, focal
Necrosis, coagtilative
Pigmentation, hemosiderin
Vacuolization
Capsule, h7rperplasia
Adrenal gland, medulla
Hyperplasia
Islets, pancreatic
Hyperplasia
Parathyroid gland
Hyperplasia
Pituitary gland
Cyst
Hyperplasia
Pars distslis, angiectasis
Pars distalis, cyst
Pars dis2alis, hemorrhage
Parsdistalisqhyperplasia
Parsintermedia;cyst
Rathke's cleft, crystals
Thyroid gland
U9timobranchial cyst
( :-cell , hyperplasis
Follicle, cyst
(55)
1 (2tYa)
5 (9%)
8
L
2
10
1
(15%)
(240)
'
(4%a)
(18°l0)
(2%)
1 (290)
' .
3 (5`~O)
(54)
13 (24%)
(53)
1 (2%)
(54)
3 (6%)
(54)
1
23
1
28
1
(2%)
(43%)
P2%1
(52%)
(2%)
(55)
Y (2%)
19 t359'o?
GENERAL BODY SYSTEM
None
Hyarmquznmne, NTP TR 366
160
(55)
f (21%)
1 (29°0)
8 (lb`~)
2 (4%)
11 (20%)
1 (2%)
1 (2`Yo~
3 (5%)
.
\ 4%D
(55)
2
4
1
3
8
i
2
12
(4%)
(7%)
(2'Yo)
(b%)
(15%)
(2qo)
(4%)
(22~01
7 (139'0)
1 (2%)
8 (15%)
(28)
11- (2090)
(55)
(22)
2 (9%)
(5d)
1 (2%)
(54)
2 (4%
(54)
1 (230)
2 (4%)
28 (33%)
20 (37%)
22 (41%)
26 (48%)
(54)
15 (28~0)
'
1 (2%)
(55)
14 (25%)
TABLE B5 . SUMMARY OF THE INCIDENCE OF NONNEOPI.tlS'I'IC LESIONS IN FEMALE RATS IN THE
TWO-YEAR GAVAGE STUDY OF HYDROQUINONE (Continued)
Vehicle Control
GENITAL SYSTEM
Clitoral gland
Abscess
Cyst
Hyperplasia.
Inflammation, chronic
Inflammation, graaauloanatous
Inflammation, suppurative
Pigmentation, hemosiderin
Ovary
Atrophy
Corpus Iuteum, cyst
Follicle, cyst
Peeiovarian tissue, cyst
Oviduct
Inflammation, chronic
Uterus
Inflammation, suppurative
Cervix, abscess
Cervix, inflammation, proliferative
Cervix, prolapse
Cervix, epithelium, degeneration, anucoad
Endometriurn, hyperplasia, cystic
Vagina
Dilatation
HEMATOPOIETIC SYSTEM
Blood
Neutrophilia
Thrombocytopenia
Erythrocyte, poikilocytosis
Bone marrow
Rdyelofabrosis
Erythroid cell, hyperplasia
Myeloid cell, hyperplasia
Lymph node
iVlediastinal, hyperplasia, macrophage
Mediastinal, hyperpTasia, plasma cell
NYediastinal, pigmentation, hemosiderin
Medaastinal, sinus, ectasia
Pancreatic, hetnatopoietic cell proliferation
Pancreatic, sinus, eckasia
Lymph node, mandibular
I-Iyperplasia, lymphoid
Iiyperplasia,macrophage
fiyperplasia, plasma cell
Sinus, ectasia
Lymph node, mesenteric
Congestion
Hemorrhage
Hyperplasia, macrophage
I-Iyperptasia, plasma cell
Sinus, ectasia
Spleen
Fibrosis
Hematopoietic cell proliferation
Infarct
Inflammation, chronic
Pigmentation, hemosiderin
(51)
1
4
2
7
(2%)
(9%)
(4%)
(14~°0)
~ (109'0)
(55)
2 , (43'0)
2 (4%)
fl (230)
(55)
2 (4%a)
2 (4%)
17 (319°0)
(2)
1 (509°0)
(8)
(55)
1 (29'o)
1 (2%)
1 (2`90)
(56)
Low Dose
High Dose
(24)
Y
2
2
1
1
1
(29)
1
1
i
1
(52)
9 (17%)
(4%)
(8%)
(8%)
(4%)
(49'0)
(4%)
5 (10%)
1' (29b)
2 (4%)
(55)
(33'a)
(39'0)
(3%)
(39'0)
1 (2%)
(55)
1 (290)
6 (11%)
1 (2qo)
26 (289'0)
(1)
(10)
2
1
1
(28)
l.
(20%)
(109'0)
(103'v)
(4%)
(55)
4 (79'0)
3 f5%?
(53)
1 (2%)
2 (4%)
1
(2%)
161
(50%)
(4%)
(7~'0)
(29'0)
1 (23'0)
15 (279'0)
(1)
(1$)
2 (Y1%)
(55)
(55)
2 (2%)
(28)
1 (2%)
1. (4%)
1 (4%)
(26)
1 (4%)
(52)
1 (2%)
& (4~'a)
2 (4%)
2 (4g'a)
1 (2%)
2 (4qo)
6 (115°0)
(55)
(4'%)
1 (296)
i (4%)
1 (2%)
2
(2)
1
(55)
B
4
fl
Z
(55)
1
5
1
1
2
Z
3
(55)
2
2
1
('Y9'o)
(2%)
(99'a)
(23'0)
(2`Yo)
(2%)
(6R'o)
(4%)
(4%)
(2'90)
I-iydroquinone, NTP TR
366
-
Vehicle .Control
HEAKATOPOIETIC SYSTEM (Continued)
Thymus
Cyst
Arteriole, mediasCinum, inflammation, chronic
IIeF'TEGLTMEDTTARY SYSTEM
Mammary gland
Abscess .
Cyst
Iiyperplasia
Mineralization
Duct, fibrosis
Skin
Abscess
Cyst epithelial inclusion
Inflammation, chronic
Ulcer
Subcutaneous tissue, cyst
Subcutaneous tissue, inflammation, chronic
Low Dose
High Dose
(52)
4 (8%)
1 (2%)
(27)
1 (4%)
(51)
5 (10%)
(55)
(55)
(54)
1 (2%)
14 (26%)'
30 (56°k)
16 (28%)
36 (65%)
1 -(2%)
(5b)
1
(2°Jo)
'
2 (43b)
12 (22%)
45 (&29b)
1 (2%)
(3tb)
1
fl
2
2
(3%)
(3%)
(7%)
(7%) .
2 (4%)
(55)
1 (2R'o)
2 (4'9'0)
1 (2%)
MUSCULOSKELETAL SYSTEM
None
NERVOUS SYSTEM
Brain
Compression
Cerebrum, mineralization
Meninges, hemorrhage
Pons, hematocyst
Ventricle, dilatation
RESPIRATORY SYSTEM
Lung
Congestion
Edema
Hemorrhage
' giyperplasia, macrophage
Hyperplasia, adenomatous
Pigmentation, hernosiderin
dnterstitium, inflammation, chronic
Interstitium, inflammation, grarauloanatous
Pleura, inflammation, chronic
Nose
Ezudate
Hemorrhage
Inflammation, chronic
Inflammation, supptu'ative
Lumen, foreign body
Nasolacrimal duct, cyst
Nasolacriacaal duct, inflammation, chronic
Idasoiacrimal duct, inflammation, suppurative
Nasolacrimai duct, xnetaplasia, squama>us
Trachea
Inflammation, chronic
Glands, cyst
fiydroquinorae, NTP TR 366
(55)
7 (13~'0)
(28)
6 (2fl%)
1 (2%)
1 (2°!0)
2 (4%)
(55)
(55)
2 (4~'0)
.
(29)
2 (7%)
23'0)
(55)
1 (2%)
1 (2'Ya)
1 (2%)
1 (2%)
1 (3~3'0)
L (3%)
1 (2g'o)
2 (4%)
3 (5%)
2 (7%)
i (29'0)
i (29'0)
3 (59'0)
(55)
1 (23'0)
1 (2%)
(b5)
(28)
1 d4%>
7 (13%)
1 (2°k)
L (2%)
4 (14%)
1 (2%)
4 (7°!0)
(71°1o)
(2~'0)
(95%)
17 (613'0)
i (2%)
28 (51%)
39
1
52
(55)
3
1
(5%)
(2%)
i62
20 (723'0)
(28)
2 (7%)
I (4g°o)
40 (73%)
(b5)
6 (11%)
j,
Vehicle Control
..
'
k . .
SPECIAL SENSES. SYSTEM
Eye
Hemorrhage
Cornea, proliferation
Retina, atrophy
Fiarderian gland
r. .at_ .' .v_a:_~
. .L ...,~. : ..
High Dose
Low Dose
(2)
fl?
2 4100%'oD .
(2)
2 (1003°o)
di)
1 (100%a)
URINARY SYSTEM
(55)
Kidney
cyst
17 (319°o)
Inflammation, chronic
3 (5%)
Mineralization
Necrosis, caagulative
47 (85%)
Pbephropathy
1 (2%)
Pelvis, dilatation
2 (4°1a)
Renal tubule, inflammation, suppurative
Transitional epithelium, hyperplasia, papillary
(55)
Urinary bladder
5 (9%)
Inflammation, chronic
Transitional epithelium, hyperplasia, papillary
163
(55)
1 (2°h)
14 (25°l0)
1 (2°k)
47 (85%)
1 (29'0)
1 (2qo)
(27)
4 (153°n)
(6)
3 (50%)
1 (173'0)
2 {339'o)
(l)
(55)
3.
18
4
i
46
(2%)
(33%)
(7%)
(2%)
(8430)
(51)
3 (69'0)
1 (2%)
Hyciroquinone, N'I'P `I'R 366
Hydroqiainone, NTF' TR 366
164
165
Hydroquinone, NTP TFt 366
TABLE CI . SUMMARY OF THE INCIDENCE OF P7EOPI.ASMS IN MALE MICE IN THE TWO-YEAR
GAVAGE STUDY OF HYDROQUINONE
Vehicle Control
Animals initially in study
Animals removed
Animals examined kaistopathologically
ALIMENTARY SYSTEM
Gallbladder
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Intestine large, cecum
Lymphoma malignant histiocytic:
Intestine large,colon
°
Lymphoma malignant lymphocytic
Intestine large, rectum
Sermsa, carcirivid tumor benign
Intestine small, ileum
Adenocarcinoma
Lymphoma malignant lymphocytic
Jejunum, lymphoma malignant lymphocytic
Intestine small, jejunum
Lymphoma malignant lymphocytic
Liver
Fabrosarcoma, metastatic, skin
gIemangioma
fiemangioma, marked
HCFri$hg10S8PC0Iri8
Iiepatocellularcarcinoma
FIepatocellular carcinoma, multiple
I-iepatvcelIular adenoma
Hepatoceliuiar adenoma, multiple
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Sinusoid, sarcoma
Mesentery
Alveolar/bronchiolar carcinoma, metastatic;
lung
Lymphoma malignant Eaistiocqtic
Lymphoma malignant lymphocytic
Pancreas
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Salivary glands
Lymphoma malignant histiocytic
Lymphoma malignantiymphocytic
Stomach, Forestomach
Papil2oma squamous
CARDIOVASCULAR SYSTEM
Heart
Alveolar/bronchiolar carcinoma, metastatic,
lung
Lymphoma malignant iymphocqtic
Pericardium, lymphoma malignant histiocytic
Hydroquinone, NZ'P TK 366
65
65
56
Low Dose
High Dose
&5
65
54
65
65
55
(4¢)
l (2%)
*(54)
(48)
(49)
*(54)
(49)
*(54)
I (2°l0)
*(54)
(50)
(4.8)
1 (2%)
1 (2%)
*(54)
(50)
*(54)
3 (6°l0)
(55)
2 (4%)
1 (23°0)
i (2%)
Y
(`L%)
12 (22%)
1 (29'0)
9 (16%)
2 (4%a)
2 (4%)
(52) .
1 (29'0)
(47)
1 (2%)
1 (2%)
(45)
(55)
1 (2%)
(2%)
11 (20%)
2 (4%)
7 (13g'o)
15 (289°o)
6 (flfl9'o)
15 (27%)
5 (99'0)
2 (49'0)
1 (23°0)
1 (29~0)
*(54)
*(35)
fl (2%)
(49)
2 (2%)
(48)
3 (2%)
I (2%)
*(5b)
1 (2'Yo)
(64)
1 (2%)
1 (29'0)
*(54)
1 (29'0)
(55)
*(54)
2 (4%)
(55)
2 (4%)
1 (2%)
*(54)
1 (2g'o)
(55)
1 (2%)
Y (2%)
(53)
(55)
*(54)
(5b)
1 (2°Jo)
1 (2°l0)
166
(53)
1 (2%)
!
MALE MICE IN THE TWO-YEAR
TABLE Cl . SUMMARY OF THE INCIDENCE OF NEOI'LASMS IN (Continued)
GAVAGE STUDY OF f$YI3R.OQiJIiVONE
Vehicle Control .
ENDOCRINE SYSTEM
Adrenal gland .
Capsule , lymphoma malignant lymphocytic
Adrenal gland, cortex
Adenoma
Adrenal gland, medulla
Phea>chromocytoma benign
Pituitary gland
Parsaistalis,adenoma
Thyroid gland
Follicular cell, adenoma
GENERAL BODY SYSTEM
Tissue, ATt9S
Carcinoma
GENITAL SYSTEM
Epididymis
Lymphoma malignant lymphocqtic
Prostate
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Seminal vesicle
Lyanphomamalignant lympisocyti c
Testes
Lymphoma malignant lymphocytic
Interstitial cell, adenoma
(55)
2 (4%)
(b4)
I (2%)
(50)
(52)
2 (4%)
(52)
3 (fi%)
* (54)
(55)
2 (4%)
(b3)
1 (29°0)
(5¢)
(50)
(54)
2 (4%)
*(55)
*(54)
1 (2%)
*(55)
(54)
(54)
(55)
4 (2%n)
*(54)
I (2%)
*(54)
2 (4%)
(55)
*(54)
1 (2%)
(55)
(55)
*(54)
(55)
I (290)
'
(55)
1. (2%)
3 (5%)
(b5)
°(b4)
(2%)
(2%)
(2%)
(2%)
(23"0)
(2%)
(2%)
(4%)
(2~o)
'
(5%)
1 (2%)
1
1
2
1
Lymph node, mesenteric
Lymphoma malignant histiacytic
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
(54)
2 «%t
3 (6%)
2 (4%)
167
(2%)
(2%)
(4°to)
(230)
'
2 (4%)
1 (2%)
I (24'0 )
g (2%)
1
Lymph node, mandibular
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
1 (2%)
1 (2R'o)
* (54)
(52)
Lymphoma malignant mixed
(54)
(53)
(55)
H1EPldA'dOPOTETIC SYSTEM
(55)
Lymph node
Alveolar/bronchiolar carcinoma, metastatic,
lung
Axill~scy, lymphoma malignant mixed
1
Bronchial, lymphoma malignant lymphocytic
1
lymphocytic
malignant
cervical,
lymphoma
Deep
1
Iliac, lymphoma malignant ixistiocytac
1
Iliac, lymphoma malignant lymphocytic
Iliac, lymphoma malignant mixed
I
Iesa'ina1, lymphoma malignant histiocytic
1
Inguinal, lymphoma malignant lymphocytic
Ianguinal, lymphoma malignant mixed
Lumbar, lymphoma malignant lymphocytic
Medaastinal, lymphoma malignant lymphocytic
Mediastinaly lymphoma malignant mixed
1
Pancreatic, lymphoma malignant histiocytic
B
Pancreatic, lymphoma malignant lymphocytic
1
Renal, lymphoma malignant histiocy2ic
3
Renal , lymphoma. malignant lymphocytic
Renal, lymphoma malignant mixed
Thoracic, lymphoma malignant histiacyl,ic
Thoracic, lymphoma malignant lymphocytic
High Dose
Low Dose
(2%)
(51)
1 (2%)
1 (2°Io)
3 (6%a)
(50)
*(54)
6 (11%)
3 (6%)
1
Ilydroquinone, NTP TR 366
TABLE Cl . SUMMARY OF THE INCIDENCE OF NEOPLASMS IN MALE MICE IN THE TWO-YEAR
GAVAt'sE STUDY OF HYDROQUINONE (Continued)
Vehicle Control
FiEMATOPOIETIC SYSTEM (Continued)
Spleen
Lymphoma malignant histaocytic
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Thymus
Lymphoma malignant lymphocytic
IN1'EGUMENTARY SYSTEM
Skin
Fzbeoma
Fsbaosagcoma
Papil9oma squamous
Subcutaneous tissue, fibrama
Subcutaneous tissue, fibroma, multiple
Subcutaneous tissue, fibrosarcoma
Subcutaneous tissue, hemangiosarcoma
Subcutaneous tissue, lymphoma malignant
lymphocytic
Subcutaneous tissue, neurofibeoma
Subcutaneous tissue, sarcoma
MUSCULOSKELETAL SYSTEM
Bone
Osteasarcoana
Skeletal muscle
IntercostaI, alveolar/bronchiolar carcinoma,
metastatic, dung
NERVOUS SYSTEM
Brain
Lymphoma malignant lymphocytic
RESPIRATORY SYSTEM
Lung
AlveoIar/bronchfoflat'sdenoma
Alveolar/bronchiolar adenoma, multiple
Alveolar/bronchiolar carcinoma
HepatocelIular carcinoma, metastatie, liver
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Nose
Mucrosa, lymphoma malignant lymphocytic
SPECIAL SENSES SYSTEM
Ear
Pinna, txistiocytic sarcoma
Harderian gland
Adenoma
Hydroquinone, NTP TR 366
(55)
(b2)
3 (5%)
(39)
2 (5%)
(55)
Z
2
1
1
Low Dose
f2R'oi
(4%)
(2%)
(2%)
5 (9%)
1 (2%)
1 (2%)
1 (296)
(54)
1 d29O?
*(5b)
4 (8%)
2 (4%) .
°(54)
*(54)
;
1 (2qo)
1 (29~a)
! (2%)
1 (2%)
(15%)
High Dose
(54)
1 (2%)
1 (23'0)
(42)
1 (2%)
(55)
1 (2%)
2 (d%'m)
1 (2%)
2 (4%)
3 (6~'0)
*(54)
(56)
*(54)
*(55)
1 (2%)
(55)
(55)
5
1
fi
5
(9%)
(2%)
(153'o)
(9%)
*(54)
1 (2~'0)
(55)
"(54)
9 (179"0)
(5b)
3
1
6
3
1
1
4 (7%)
3 (5~'0)
1 (2°k)
(55)
`°(54)
1 (25'0)
(55)
*(55)
*(54)
I (23'0)
*(54)
2 (P4%)
*(55)
*(5b)
5 (9°l0)
168
(5%)
(2%)
(11%)
(5%)
(2%)
f2%D
*(5fi)
6 (li%a)
i
1
I
TABLE Ci . SUMMARY OF THE INCIDENCE : 0F~PdE(DPLASIIRS IN MALE MICE IN THE TWO-YEAR
GAV!lGIE STUDY OF H'iCI9ROQLJYNCDIVE (Continued)
;
i
Vehicle Control
URINARY SYSTEM
Kidney
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Lymphoma malignant mixed .
Renal tubule, carcinoma
Urinary bladder
Lymphoma malignant lymphocytic
SYSTEMIC LESIONS
Multiple organs
Lymphoma malignant lymphocytic
Lymphoma malignant histiocytic
I-Iemaatgiosarcoma
EIemangioma
Lymphoma malignant mixed
(55)
1 (2%)
I (29'0)
1 (2%)
*(64)
(56)
1 (230)
2 (4%)
(b4)
i (2%)
*(55)
4
2
i
1
High Dose
Low Dose
.
(7%)
(4%a)
(2%)
(2%a)
*(54)
(55)
*(54)
9 (17%)
1 (2%)
2 (4%)
*(55)
4
2
3
4
1
ANIMAL DISPOSITION SUMMARY
Animals initially in study
Terminal sacrifice
Moribund
Dead
Interval sacrifice
Wrong sex
65
33
12
BO
10
65
37
10
7
10
1
65
36
6
14
10
TUMOR SUMMARY
Total animals with primary neoplasms *"
Total primary neoplasms
Total animals with benign neoplasms
Total benign neoplasms
Total animals with malignant neoplasms
Total malignant neoplasms
Total animals with secondary neoplasms
Total secondary neoplasms
39
?9
23
38
30
41
7
9
46
84
31
41
34
43
44
69
29
41
23
28
.
(73'0)
(4%)
(5%)
(2%)
(2%)
4
* Number of animals receiving complete necropsy examination; all gross lesions including masses examined microscopically .
Primary tumors : all tumors except secondary tumors
*** Secondary tumors: metastatic tumors or tumors invasive into an adjacent organ
169
Hydroquinone, NTPTFt 366
STUDY
CARCASS
ID
ALIMENTARY SYSTEM
Esaphagus
Galibladdex
Lymphoma malignant lymphocytic
Intestine largo
Intestine large , cecum
Intestine large, colon
Intestine large, rectum
Intestine small
Intestine small, duodenum
Intestine small,ileum
.
Adenocarcinoma
Lymphoma malignant lymphocytic
Intestine small, jejanum
Liver
Fibrosarcoma, metastatic, skin
Hemangioma, marked
Semangiosaxcoma
Repatocellularcarcinoma
Hepatocellularcarcinoma, multiple
Hepatocetlularadenoma
Lymphoma malignant histiocytic
Lymphoma malignant Iymphocytic
Mesentery
Alveolar/bronchiolar carcinoma,
metastatic, lung
Pancreas
Lymphoma malignant lymphocytic
Salivary glands
Lymp homa mali gnant lymp hocytic
Stomach
Stomach, forestamach
Papiltoma squamous
Stomach, glandular
Tooth
0
2
0
5
0
5
0
5
0
4
4
0
1
4
7
3
1
3
3
4
3
3
9
3
1
2
0
1
2
0
2
3
4
2
-F
M
+
i-
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. WEEKS
STUDY
N
CARCASS
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ALIMENTARY S .
Esophagtts
Gallbladder
Lymphoma malignant lymphocytic
Intestine large .
Intestine large, cecum
Intestine large, colon
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Intestine small, duodenum
Intestine small, ileum
Adenocarciaoma
Lymphoma malignant lymphocytic
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Liver
Fibmsarcoma, metastatic, skin
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Hemangiosarcoma
Hepatocellularcarcinoma
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-
.
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gland
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Hydroquinane, NTP T1Z 366
TABLE C2 :° INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE MICE : VEHICLE CONTROL
(Continued)
i
o
5
i
a
5
i
o
5
a
0
5
a
0
5
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2
3
9
0
0
1
1
1
2
1
CARCASS
ID
Eso~hagus
Gallbladder
Lymphoma malignant lymphocytic
Intestine large, cecum
Intestine large, colon
Intestine large, rectum
Intestine small
Intestine small, duodenum
Intestine small, ileum
Adanocarcinoma
Lymphoma malignant lymphocytic
Intestine small, jejunum
Liver
Fibrosarcorda, metastatic, skin "
He maagioma, marked
FTemangiosarcoma
Hepatocellulaz carcinoma
FTepatoce}lnlar carcinoma, multiple
Flepatocellular adenoma
Lympboma malignant histiocytic
Lymphoma malignant lymphocytic
Mesentery
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metastatic, lung
+
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metastatic, lung
Lymphoma malignant Iymphocytic
+
+
+
+
+
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Adrenal gland, cortex
Adenoma
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Pbeochromocytoma benign
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+
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Stomach
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.
+
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44
1
50
49
49
50
50
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1
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6
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1
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2
55
55
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55
6
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55
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54
1
53
46
50
3
55
2
--
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Coagnlating gland
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Hydroquznone,NTP TR 366
2
54
1
12
55
1
55
55
1
172
TABLE C2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE MICE : VEHICLE CONTROL
(Continued)
0 0 --o-00 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1
WEEKS x
STUDY
CARCASS
ID
£
Bone marrow
Lymph node
Bronchial, lymphoma malignant
lymphocytic
Deep cervical, lymphoma malignant
lymphocytic
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Iliac,lymphoma malignant lymphocytic
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lymphocytis
Pancreatic, lymphoma malignant
histiocytic
Pancreatic, lymphoma malignant
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Lymph node, mandibular
Lymphoma malignant lymphocytic
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Lymphoma malignant lymphocytic
Spleen
Lymphoma malignant lymphocytic
Thymus
Lymphoma malignant lymphocytic
T
Osteosarcoma
Skeletal muscle
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carcinoma, metastatic, lung
Brain
Spinal cord
RES
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Fiepatocellular carcinoma, metastatic,
liver
Lymphoma malignant lymphocytic
Nose
Trachea
7
7
8
0
8
7
8
7
9
0
9
1
9
3
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.
+
t
+
+
+
+
+
+
+
+
f-
+
+
+
+
-F
t
.
+
+
+
+
+
+
+
t
+
9- +
i-
+
+
+
+
+
+
+.
t
+
+
+
+
+
+
-F
+
+
+
+
+
7C
+
+
7;
+
+
+
+
$liE
Eye
Harcerian gland
Adenoma
Kidney
Lymphoma malignant tymphocytic
Urethra
Urinary bladder
Lymphoma malignant lymphocytic
1
6
1
PapilIoma squamcus
M
Bone
1
5
8
+
+
Mammary gland
Skin
FiUroma
Fibrosarcoma
Subcutaneous tissue, fibroma
Subcutaneous tissue, fibrosarcoma
Subcutaneous tissue, lymphoma
malignant lymphocytic
Subcutaneous tissue, neurofibroma
Subcutaneous tissue, sarcoma
1
5
0
4
8
+
t
+
+
+
.
+
+
+
+
-6-
+
X
+
+
+
+
+
+
4
+
+
+
+
+
+
173
.
X
R
.
X
x
+
'+
+
+
+
+
+
+
R
.
t
+
+
+
+
+
+
+
t.
+
+
+
X
+
+
+
+
.
+
+
+
+
+
+
+
~+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
+
+
-F
+
+
t
+
+
+
+
+
+
a- +
+
+
.
+
+
Hydroquinone, NTP TR 366
HO .~GY OF MALE MICE : VEHICLE CONTROL
TABLE C2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY
(Continued)
WEEKS
STUDY
N
CARCASS
ID
"L
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
Y
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
I
0
5
1
0
5
1
0
5
1
0
5
!
0
5
1
0
5
1
0
5
1
0
5
~
5
5
6
8
1
S
2
8
3
9
2
0
3
2
3
3
3
1
1
2
1
2
2
3
2
4
1
6
2
7
2
1
1
2
2
3
2
u
3
1
5
1
6
1
7
1
+
+
+
+
+
+
+
f
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
-F
+
. +
+ '+
3
Lymph node
Bronchial, lymphoma malignant
lymphoeytic
Deep cervical, lymphoma malignant
lymphocytic
I1iac, lymphoma malignant histiocytic
Iliac,lymphoma malignant lymp&ocytic
Inguinal, lymphoma malignant
histiocytic
Inguinal, lymphoma malignant
lymphocytic
Pancreatic, lymphoma malignant . ,
histiocytic.
Pancreatic, lymphoma malignant
lymphocytic
Renal, lymphoma malignant histiocytic
Renal, lymphoma malignant lymphocytic
Lymph node, mandibular
Lymphoma malignant lymphocytic
Lymph node, mesenteric
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Splee¢
Lymphoma malignant lymphocytic
Thymus
Lymphoma malignant lymphocytic
Mammary gland
Skin
Fibroma
Fi6rosarcoma
Papilioma squsmous
Subcutaneous tissue, fibroma
Subcutaneous tissue,fibrosarcoma
Subcutaneous tissue, lymphoma
malignant lymphocytic
Subcutaneous tissne,neuro6broma
Subcutaneous tissue, sarcoma
3
+
-r
+
+
Bone marrow
3
2
+
+
+
+
+
+
+
+
+
x
,
x
.
+
+
.
-
.
-
+
+
+
~-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-t-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+ -+
M
+
M
+
M
+
M
+
X
.
.
+
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
M
+
+
M
+
M
+
+
+
+
+
+
+
+
+
.
+
+
+
M
+
M
+
M
+
M
+
M
+
M
+
M
+
M
+
M
+
M
+
M
.
M
+
M
+
+
"R
-s-
n1
+
M
+
M
+
M
+
M
+
+
+
+
+
+
+
+
+
M
+
+
+
'+
+
M
+
X
X
(
Osteosarcoma
Skeletal muscle
Intercostal, alveoIarlbronchiolar
carcinoma, metastatic, lung
j
Brain
+
+
+
+
+
+
+
+
-F
+
+
+
+
+
-i-
+
+
+
+
+,
+
+
+
+
+
-7-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-F
+
+
+
+
+
-7i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
-+
+
+
Spinal cord
Lung
Alveolarlbronchiolaradeaoma
Alveolar/bronchiolar adenoma, multiple
Alveolarlbronchiolarcarcinoma
Hepatocellular carcinoma, metastatic,
liver
Lymphoma malignant lymphocyt'sc
Nose
Trachea
S~CIICL SE
Eye
Harderian gland
Adenoma
+
i-
+
+
¢
+
+
+
+
+
+
E
Hydroquinone, NTP TIt 366
+
+
+
.
+
+
+
+
+
+
+
+
%
7{
~RYIQAT~
Kidney
Lymphoma malignant lymphocytic
Urethra
Urinary bladder
Lymphoma malignant lymphocytic
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
174
-
I
WEEKS ON
STUDY
CARCASS
ID
Bone marrow
Lymph node
Bronchial, lymphoma malignant
lymphocytic
Deep cervical, lymphoma malignant
lymphocytic
- Iliac, lymphoma malignant histiocytic
Iliac, lymphoma malignant lymphocytic
Inguinal, lymphoma malignant
kistixytic
Inguinal, lymphoma malignant
i
i
i
0
5
0
5
0
5
9
1
0
1
+
+
+
+
.
i
t
0
5
0
5
0
2
Z
1
3
I
+
f
+
+
-t+
TOTAL:
TISSUES
TUMORS
.
55
55
.
.
.
,
,
.Y SYSTEM
Mammary gland
Skin
Fibroma
Fibrosarcoma
.
Papilloma sqvamous
Subcutaneous tissue, fibzoma
Subcutaneous tissue,fibrosarcoma
Subcutaneous tissue, lymphoma
malignant lymphocytic
Subcutaneous tissue, neurofibroma
Subcutaneous tissue, sarcoma
MUSCULOSKELETAL SYSTEMBone
Osteosarcoma
i,
1
1
1
i
2
lymphocytic
Pancreatic, lymphoma malignant
histiocytie
.
Pancreatic, lymphoma malignant
lymphocytic
Renal, lymphoma malignant histiocytic
Renal, lymphoma malig. lymphocytic
Lymph node, mandibular
Lymphoma malignant lymphocytic
Lymph node, mesenteric
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Spleen
Lymphoma malignant lymphocytic
Thymus
Lymphoma malignant iymphocytic
1
.
. .
.
1
X
+
+
+
X
+
+
+
+
M
+
i-
+
+
+
+
M
+
X
+
.
+
N%
+
M
+
M
+
M
+
M,
+
-
.
2
1
3
52
-
54
2
3
55
3
39
2
.
+
1
55
.
5
1
.
-
.
+
5'S
+
+
+
+
+
+
+
-i-
+
55
3
+
+
+
+
X
+
55
Skeletal muscle
Intercostal,alveo(ar/bronchiolar
carcinoma, metastatic, lung
t~RVOUS
Brain
Spinal cord
$
Lung
Alveolarlbronchiolar adenoma
Alveolaribronchialar adenoma, multiple
Alvoolarlbronchiotar carcinoma
Hepatocellular carcinoma, metastatic,
liver
Lymphoma malignant lymphocytic
Nose
Trachea
X
5
+
+
+
+
+
+
+
.
55
55
i+
SPECIAL SENSES SYSTEM
Eye
Harderian gland
Adenoma
URINARY SYSTEM
Kidney
Lymphoma malignant lymphocytic
Urethra
Urinary bladder
Lymphoma malignant lymphocytic
5
+
+
+
+
+
+
+
+
e-
-1+
+
.
175
,
55
3
54
I-iydroquinone, NTP'I'R 366
.
TWO-YEAR GAVAGE
TABLE C2. INDIVIDUAL ANIMAL .TUMOR PATHOLOGY OF MALE MICE IN THE
STUDY OF fYYDRaDQITINONE : LOW DOSE
WEEK
STUDY
CARCASS
ID
0
0
3
P3
.
3
4
Esophagus
Ga}lbladder
Intestine large
Intestine large, cecum
Intestine large, colon
Lymphoma malignant lymphocytic
Intestine large, rectum ,
Zntestinesmall .
Intestine small, duodenum
Intestine small, ileum
Lymphoma malignant lympbocytic
Intestine small, jejunum.
Lymphoma malignant lymphocytic
Liver
Hemangiosarcoma
Hepatocellularcarcinoma
Fiepatocetlnlaiadenoma
Hepatocellnlar adenoma, multiple
Lymphoma malignant lymphocytie
Sinusoid, sarcoma
Mesentery
Lymphoma malignant lymphocytio
Pancreas
Lymphoma malignant lymphocytic
Salivary glands
Lymphoma malignant lymphocytic
Stomach
Stomach, forestomach
Stomach, glandular
Tooth
Heart
0
5
3
0
6
3
0
6
7
0
6
9
0
7
9
0
8
6
0
9
3
0
9
4
0
9
4
0
9
4
0
9
4
0
9
5
0
9
8
4
9
9
0
9
9
1
0
1
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
6
4
5 . 5
6
3
7
5
0
5
3
3.
6
5
7
4
3
2
1
5
4
3
9
5
4
1
0
3
7
3
9
4
4
2
7
2
8
5.
9
2
9
3
0
1
0
2
1
1
+
A
+
A
+
+
A
+
A
A
+
A
+
+
t
+
+
+
+
+
+
Pd
+
+
+
+
+
'r
+
+
+
+
+
+
+
+
+
A
+
A
A
A
+
+
+
M
+.
+
+
A
A
+
+
+
+
+
-0
3
2
+
+
A
.
.
+ + +
+ + +
+ A +
+ . . , +
+
+ ,
.
. +
+
+
+
+
A
.
A
+` +
'
+
+
X
-h
+
.
Adrenal gland
Capsule, lymphoma malignant
lymphocytic
Adrenal gland, cortex
Adenoma
Adrenal gland, medulla
Pheochromocytoma benign
Islets, pancreatic
Parathyroid gland
Pituitary gland
Thyroid gland
Follicnlar cell, adenoma
+
+
-F
t
+
+
+
+
+
+
+
+
+
+
+
dM
+
-F
+
+
+
+
+
+
A
+
.
+
+
+
+
+
+
+
+
+
+
-h
+
+
-F
+
-h
+
+
+
+
+
+
+
+
+
i-'
+
+
+
+
+
+
+
+
+
+
+
+
+
A
+
X.
A
R
R
+
+
+
-t~
fe
-h
+
+
t-
+
+
+
+
X
1S
%
X
X
X
.
+
R
+
..
_
.
,
.
+
+
+
.
+
f
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
+
h
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
NL
+
+
+
+
+
+
+
i-
+
+
d-
+
+
+
.
+
+
+
+
+
+
M
+
+
+
+
+
i-
.
A
+
+
+
A
+
+
+
+
+
+
+
+
r
+
+
+
+
+
+
+
+
a-
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
A
+
-h
+
+
+
-F
+
+
+
+
+
+
+
+
+
+
+
+
+
M
M
+
+
+
+
+
+
+
+
M
+
+
+
+
+
+
M
M
+
+
+
M
+
+
+
j"
+
+
+
+
+
+
+
.
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
-F
.+
+
+
+
.
-
+
+
t
+
¢
+
+
+
~-
+
k
-I+
+
+
+
+
+
+
+
+,
+
+
+
+
+
+
+
+
+
.
.
+
+
+
+ ,
+
+
t
+
+
+
+
+
+
+
+ . +
+
+
+
+
+
+
+
+
+
+
+
+
+
I-Iydroquinone9 N'I'P Tlt 366
+
+
-7-
.
+
176
t
.
-
+
+
+
±
.
X
+
+
+
+
+
+
'+
+
+
+
-+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
~-
+
++
Tissve,NOS
Carcinoma
Coagulating gland
Epididymis
Lymphoma malignant lymphocytic
Preputialglaad
.
.
Prostate
Lymphoma malignant tymphocytic
Seminal vesicle
Lymphoma malignant lymphocytic
Testes
Lymphoma malignant lymphocytic
+
+
R
+
A
.
-
+
.
.,
,
+
CE : LOW DOSE
TABLE C2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE
(Continued)
WEEKS
STUDY
1V
CARCASS
ID
~v
'I~~Y2~5
Esophagus
GetlbFadder
Intestine large
Intestine 3arqe,cecum
Intestine large, colon
Lymphoma malignant lymphocytic
Intestine large, rectum
Intestine small
Intestine small, duodenum
Intestine small, ileum
Lymphoma malignant lymphocytic
Intestine small, jejunum
1
0
5
1
0
5
1
0
5
I
0
5
1
0
5
L
0
5
2
0
5
1
0
5
I
1
11
1
0
0
0
0
0
5
5
5
5
5
8
8
3- 4
2
4
3
1
4
1
5
2
5
3
6
2
6
4
5
1
1
0
5
1
0
5
10
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
1 . I
0 . 0
0
5
5
5
1
2
1
3
1
4
2
5
4
2
5
4
5
3
5
4
6
2
8
1
8
2
'
.
.
Hemangiosarcoma
Hepatocollutarcarcinoma
HepatoceIlularadenoma
Hepatocallularadeaoma,multiple
Lymphoma malignant lymphocytic
Sinusoid, sarcoma
Mesentery
Lymphoma malignant lymphocytic
Pancreas
Lymphoma malignant lymphocytic
Salivary glands
.
i-
X
%
+
+
A
x
+
+.
k
+
R
+
+
X
+
f
+
X
+
+ -f
+
+
R
+; +
+
.,
%
X
X
X
.
Lymphoma malignant lymphocytic
-
,
.
Stomach
Stomach, forestomach
Stomach, glandular
Tooth
9
t
.
+
+
+
7
1
.
t
"
6
1
.
.
Lymphoma malignant lymphocytic
Liver
5
2
-
-
.
.
.
+ . +,
.
.
-
.
ARf5IU9A~TUUAR SYSTEM
Heart
Adrenal gland
Capsule, lymphoma malignant
+
Adrenal gland, cortex
Adenoma
Adrenal gland, medulla
.?hexhromocytoma benign
Islets, pancreatic
Parathyroid gland
Pituitary gland
Thyroid gland
Follicular cell, adenoma
+
,-
t
+
+
+
+
+
lymphocytic
Tissue, NOS
+
+
+
-
+
t
+
+
+
+
+
f
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
,-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
X
+
+
+
.
.
+
+
+
+
+
+
+
X
+
M
+
+
+
+
+
+
+
+
r
h
+-
+
+
+
+
+
.
+
+
+
+
+
+
t
o
YSTEM
+
.
Carcinoma
GEN
Coagulating gland
Epididymis
Lymphoma malignant lymphocytic
Preputial gland
Prostate
Lymphoma malignant lymphocytic
Seminal vesicle
Lymphoma malignant lymphocytic
Testes
+
.
I
.
+
+
Lymphoma malignant lymphocytic
177
Hydroquinone, NTPTR 366
LOW DOSE
TABLE C2 . INDIVIDUAL ANIMAL TUMOR PATHOLOGY (}F MALE MICE :
(Continued)
WEEKS
STUDY
CARCASS
ID
Esophagus
Ga llbl add er
Intestine large
Intestine large, cecum
Intestine large,colou
Lymphoma malignant lymphocyCic
Intestine large, rectum
Intestine small
Intestine small, duodenum
Intestine small, ileum
Lymphoma malignant lymphocytic
.Intestine small, jejunum
Lymphoma malignant lymphocytic
.
Liver
,
Hemangiosarcoma
Hepatocallular carcinoma
Fiepatocellvlaradenoma
Hepatocellularadenoma,multiple
Lymphoma malignant lymphceytic
Sinusoid, sarcoma
Mesentery
Lymphoma malignant lymphocytic
Pancreas
Lymphoma malignant lymphocytic
Salivary glands
Lymphoma malignant lymphocytic
Stomach
Stomach, forestomacfi
Stomach, glandular
Tooth
Heart
IUV
7.
(a
5
1
0
5
1
D
5
~``z
2
2
?
L
2
3
5
1
B
1
1
p
0
5
5
N
'
TOTAL:
T ISSUES
T UMORS
17
11
15
13
.
14
15
16
10
10
+
+
7C
+
.
,
+
13
.
+
+
+
,
K
3
54
.
11
15
.
-
15
1
16
.
15
15
15
I
'
M
Adrenal gland
Capsule, lymphoma malignant
lymphocytic
Adrenal gland, cortex
Adenoma
Adrenal gland, medulla
Pheochromocytoma benign
Islets, pancreatic
Parathyroid gland
Pituitary gland
Thyroid gland
Follicular cell, adenoma
.
1
4
17
+
+
+
+
+
+
+
+
+
+
+
-t-
+
+
+
t
+
+
+
'
+
53
.
2
52
2
.
$2
15
15
14
53
.
.
~~FT$
1
Tissue, NOS
Carcinoma
1
U`~i~T'1'rTG-SY$'i`
1
Coagulating gland
Epididymis
17
Lymphoma malignant lymphocytic
Preputial gland
Prostate
Lymphoma malignant lymphocytic
Seminal vesicle
Lymphoma malignant lymphocytic
Testes
Lymphoma malignant lymphocytic
Hydroquinone, NTP TiZ 366
.
9
17
2
17
1
18
1
179
WEEKS
STUDY
N
CARCASS
TD
HEMATOPOIETIC SYSTEM
Bone marrow
Lymph node
Asillary, lymphoma malignant mixed
"
Ingufinal, lymphoma malignant mixed
Lumbar, lymphoma malignant lymphocytic
Mediastinal, lymphoma malignant
Iympbocytic
Riediastinal, lymphoma malignant mixed
Pancreatic, lymphoma malignant
1ymphocytic
Renal, lymphoma malignant lymphocytic
Renal, lymphoma malignant mixed
Thoracic, lymphoma malignant
lymphocytic
Lymph node, mandibular
Lymphama malignant lymphocytic
Lymphoma malignant mixed
Lymph node, mesenteric
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Spleen
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Thymus
Mammary gland
Skin
Fibroma
Fibrosarcoma
Subcutaneous tissue, fibroma
Subcutaneous tissue, fibroma, multiple
Subcutaneous tissue,fibrosarcoma
Subcutaneous tissue,sarcoma
MUSCULOSKELETAL SYSTEM
Hone
NERVOUS SYSTEM
Brain
Lymphoma malignant lymphocytic
TRA
Y -SYSTEM
Lung
AlveolarlbronchioYaradenoma
A1veoLarl6ronchioIar carcinoma
Nose
Mucosa, lymphoma malignant lymphocytic
Trachea
0
0
3
0
3
2
6
5
3
0
6
3
0
6
7
0
6
9
0
7
9
0
8
6
0
9
3
0
9
4
0
9
4
0
9
4
0
9
4
0
9
5
0
9
8
0
9
9
0 - 1
9
0
9
1
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
S
1
0
5
3
4
6
S
4
5
6
3
7
5
0
5
3
3
6
5
7
4
3
2
1
5
4
3
8
5
4
2
0
3
7
3
9
4
4
2
7
2
8
S
9
2
9
3
0
1
0
2
1
1
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ +
. . .
+
+
+
+
+
+
+
+-
+
i-
+
+
+
+
+
X
+
M
+
+'
+
+
+
"
X
+
R
.
+
+
X
t
M
+
+
+
+
A
+
+
X
+
+
+
A
+
+
+
+
A
a-
+
X
+
+
+
+
+
+
IYl
M
+
M
P/C
+
+
M
+
M
+
M
+
M
-r
M
+
M
+
M
+
X.
+
+
+
+
+
+
+
+
.
+
+
+
+
+
- +
+
+
+
+
+
+
+
+
+
+
+
+
.
A
+
+
+
+
+
+
+
+
+
+
+
+
+
A
+
+
+
t
+
+
+
+
i-
+
+
X
+
M
+
R
+
+
+
X
+
+
+
+
+
+
+
A
M
+
+
+
%
+
M
M
M
+
M
+
M
+
M
+
8
R
M
+
M
+
2v1
.
+
.
X
+
+
t
.
. .
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
X
t
+
+
+
+
+
+
+
+
+
X
,
+
+
+
+
+
X
+
+
+
-t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
X
+
+
+
+
+
+
+
+
+
+
X
X
X
.
X
i-
+
+
+
X
X
+
X
+
+
+
X
SPECLkL SENSES SYSTEM
Ear
Pinna, histiocytic sarcoma
Harderian gland
Adenoma
Lacrimat gland
URINARY SYSTEM
Kidney
Lymphoma malignant lymphocytic
Urinary bladder
179
X
+
HydTOE(ll1F'20r1e, NTP `I`R 366
: LOW DOSE
TABLE C2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE MICE
(Continued)
WEEKS
STUDY
Pt
.
CARCASS
ID
'
Bone marrow
Lymph node
Axillary, lymphoma malignant mixed
In inal, l m I~oma malignant mixed
Lumbar, lym pPhoma maligna nt lymphocytic
Mediastinal, lymphoma malignant
lymphocytic
n3ediastinal, lymphoma malignant mixed
Pancreatic, lymphoma malignant
tymphocytic
Renal, lymphoma malignant lymphorytic
Renal, lymphoma malignant mixed
Thoracic, lymphoma malignant . . .
.
lymphocytic
:
Lymph node, mandibviar
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Lymph node, mesenteric
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
I
0
5
1
I
0
0
5-5
1
0
5
1
9
5
1
0
5
1
0
5
I
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
2
1
3
1
4
2
5
4
2
5
4
5
3
5
4
8
1
8
2
8
3
8
4
2
4
3
1
4
1
5
2
5
3
6
2
8
4
5
2
5
2
6
2
1
1
9
1
+
X
K
-
+
S
2
t-
+
+
+
+
+
+
+
X
.
.
.
. _.
.
+
+
Spleen
Lymphoma malignant lympbocytic
Lymphoma malignant mixed
Thymus
Mammary gland
Skin
Fibroma
Fibrosarcoma
Subcutaneous tissue, fibroma
Subcutaneous tissue, fibroma, multiple
Subcutaneous tissue, fibmsarcoma
Subcutaneous tissue, sarcoma
+.
+
.
.
+
..
+ .
.
+
+
+
+
-h
+
+
. . .
+
+
+
-F
+
..
.
,
.
+
t
-F
i-
i-
+
t
`
+
+
+
+
+
+
+
~IST E
Ear
sarcoma
Pinna, bist'socytic
Harderian gland
Adenoma
Lacrimal gland
Kidney
Lymphoma malignant lympbocytic
Urinary bladder
Hydroquinone,NTP TR, 366
+
+.
+
.
i-
+
+
+
+
-
+
.
+
T
Brain V
Lymphoma malignant lymphocytic
Lung
Alveolar/bronchiolar adenoma
Alveolarlbroncbiolarcarcinoma
Nose
Mneosa, lymphoma malignant lymphocytie
Trachea
. .
+
.
$040
,
.
'
.
+
t
X
+
+
+
R
+
iX
+
+
X
~
-
,
180
_
-
+
X
TABLE C2a INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE MICE : LOW DOSE
(Czantinued)
WEEKS ON
STUDY
.
CARCAS S
ID
Bone marrow
Lymph node
Axilkary, lymphoma malignant mixed
Iaguinal, lymphoma malignant mixed
Lumbar, lymphoma malig. lymphocytic
A2edias4inal, lymphoma malignant
. lymphocytic
RSadiastinal Lymphoma malig. mixed
Pancreatic, lymphoma malignant
lymphocytic
Renal, lymphoma malig, lymphocytic
Renal, lymphoma malignant mixed
Thoracic, lymphoma malignant
lymphocytic
Lymph node, maadibular
Lymphoma malignant lymphocytic
Lqmphoma malignant mixed
Lymph node, mesenteric
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
5 taen
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Thymus
Mammary gland
Skin
Fibroma
Flbrosarcoma
Subcutaneous tissue, fibroma
Subcutaneous tissue, fibroma, multiple
Subcutaneous tissue,C~brosarcoma
Subcutaneous tissue, sarcoma
1
0
5
1
0
5
1
0
5
1
0
S
1
0
5
2
2
1
2
2
2
2
2
3
2--,r
5
6
2
1
-
..
TOTAL:
TISSUES
TUMORS
.
+
.
.
..
+
+
Z
1
2 ..
.
+
7C
}
17
29
17
3
23
+
+
52
10
+
+
.
33
1
,
-
Bone
32
Brain
Lymphoma malignant lymphocytic
Lung
Aieeolar/bronchiolar adenoma
Alveoladbronchiolar carcinoma
Nose
ritncosa,lymphoma malig, lymphocytic
Trachea
,
17Z
+
R
+
X
%
iR
+
31
17
1
16
Ear
Pinna, histiocytic sarcoma
Harderiaa gland
Adenoma
Lacrimal gland
1
R7SV .4TbY S~S
Kidney
Lymphoma malignant lymphocytic
Urinary bladder
17
15
181
Hydroquinasne, NTP TR 366
TABLE C2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY OF MALE MICE IN THE TWO-YEAR GAVAGE
STUDY OF HYDROQUINONE : HIGH DOSE
WEEKS ON
STUDY
ALIMENTARY SYSTEM
Esopbaavs
Gallbiadder
Lymphoma malignant mixed
Intestine large
Intestine large, cecum
Lymphoma malignant hisLiocytic
Intestine large, colon
Intestine large, rectum
Serosa, carcinoid tumor benign
Intestine small
Intestine small, duodenum
Intestine small, ileum
Lymphoma malignant lymphocytic
Jejunum, lymphoma malignant
0 0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
9
6
1
3
0
1
1
2
3
4
4
5
5
8
8
8
9
0
5
5
5
5
5
5
-3
1
- 5
3
9
5
2
9
4
2
7
4
3
8
1
2
8
4
2
7
3.
3
5
5
3
3
3
3
6
3
3
5
4-
3
3
2
3
7
5
3
2
5
3
1
3
3
1
1
3
7
4
3
7
3.
3
4
4
2
8
3
2
9
5
3
0
3
0
4
2
3
2
4
+
+
.
.
Intestine small;jejunum
_
Liver
Hemeagioma
Hemangiosarcoma
HapatocolluIar carcinoma
Aepatacellnlac adenoma
HepatocalluIaradenoma, multiple
Lymphoma malignant histiocyCic
Lymphoma malignant mixed
Mesentery
Lymphoma malignant histiocytic
Pancreas
Lymphoma malignant mixed
Salivary glands
Lymphoma malignant hisEiocytic
Lymphoma malignant lymphocytic
Stomach
Stomach, forestamach
Stomach, glandular
Tooth
Pericardinm,lymphoma malignant
histiocytic
0 00 0- o -o- -0
8
4 6 7 8 8 s s s s s s s s s s s s
CARCASS
ID
CARDIOVASCULAR SYSTEM
Heart
0
+
+
+
.
+
+
+
+
+
+
M
+
+
+
+
+
M
+
M
ii-
+
A
+
rL
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-V~
+
+
+
+
+
°
+
+
A
A
+
A
+
+
+
+
+
+
+
+
A
A
+
+
+
A
+
+
.
+
+
A
+
A
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
A
A
.4
+
A
A
+
+
+
+
+
i-
A
A
+
+
A
+
A
+
+
i-
+
+
A
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
M
.4.
A
A
+
+
A
A
A
A
;F
i-
+
+
+
,+
i-
A
A
A
+
+
+
+
+
A
+
+
+
-;-
A
A
A
+
+
A
+
+
+
+
+
+
-7t
+
+
+
f
+
4
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+.
+
+
A
A
A
A
-t-
+
+
R
+
A
+
-F
A
A
+
+
+
+
+
+
+
+
+
X
X
t
+
+
+
+
+
+
+
-F
X
+
R
+
Adrenal gland
Adrenal gland, cortex
Adrenal gland, medulla
Islets, pancreatic
Parathyroid gland
Pituitary gland
Thyroid gland
Follicular cell, adenoma
+
+
i-
+
+
X
I6
X
.
s 0 0 0 0 0 0 0
+
%
+
+
B
X
-I-
+
+
+
.
+
+
+
+
X
:C
+
+
+
A
+
.
A
+
+
+
+
+
+
+
-F
+
.
+
+
+
+
+
+
+
+
+
+
+
X
+
+
+
+
+
+
¢
+
+
+
+
.
T
+
+
+
+
+
+
+
+
+
-t-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
M
+
+
+
+
+
t+
+
+
+
+
+
+
.
+
,-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
'+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
M
+
+
+
+
+
+
+
M
+
t
+
+
+
A
+
+
+
+
+
+
+
M
+
+
+
+
.
+
+
+
t
aa
a+
+
+
+
+
+
+
+
+
-h
+
+
+
+
+
+
+
+
+
+
+
-F
M
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
X
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
M
+
+
+
+
+
+
M
+
+
+
+
-t+
+
M
+
+
+
+
+
+
.
+
+
+
+
+
t
-h
+
+
+
+
h
+
+
+
+
+
+
M
+
+
+
m .
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-h
+
+
i-
+
+
+
+
+
+
+
+
+
+
-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-h
+
+
+
+
+
+
+
+
i-
+
X
.
+
GENERAL 13ODY SYSTEM
Tissue, NOS
GENITAL SYSTEM
Coagulating gland
Epididymis
Preputiat gland
Prostate
Lymphoma malignant mixed
Seminalvesicle
Testes
Interstitial cell, adenoma
HydI'OqL8111OI2B, NTP TR 366
+
+
+
+
+
+
+
182
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
,
',
',
wr:M" ON
_
STUDY
-11 1
1
1
1
1
1
5
5
5
5
5
0 0 0 0 0 0 01 01 01
5
5
5
5
1
7
2
7
1
7
2
8
2
9
2
9
3
0
2
2
3
2' 1
+.
+
+
+
+
+
+
+
+
+
+
+
+
+
+.
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
+
+
-F
+
+
+
+
+
+
+
-h
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
+
+
0 0 0
CARCASS
ID
Esophagus
Cra~~bladder
Lymphoma malignant mixed
In testinelarge
,
. .
Intestiue large , rectum
cacum
.
Lymphoma malignant histiocytic
Intestine large, colon
~
..
Yntestiae Iarge ,
Serosa, carcinoid tumor benign
Intestine small
Intestine small, duodenum
Intestine small, ileum
Lymphoma malignant lymphacytic
Jejunum, lymphoma malignant
lympgayt;C
_;
Intestine small, jejunum
Liver
.
.
Hemangioma
Hemangiosarcoma
Hepatocellalarcarcinoma
Hepatocellutaradeaoma
F¬eQatocelluTaradonoma, multiple
Lymphoma malignant histiocytic
Lymphoma malignant mixed
,
5
5
5
5
3
B
2
-i+
+
+
+
+
+
+
+
X
g
g
1
1
1
5
5
5
5
5
1 1 1 1
0 0 0 0 0 10 01 01
5
5
5
4
3
5
2
6
8
1 -4
8
1
9
1
0
1
1
2
+
+
+
+
+
+
+
+
+
M
+
+
+
+
+
+
-~i-
+
+
+
+
.
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+.
+
+
+
+
+
+
+
+
+
-F
+
+
+
+
+
0 0 0 0 0
+
x
+
R
X
.
1
+
+
1
i-
+
x
Mesantery
Lymphoma malignant histiocytic
Pancreas
Saliva
Lymphoma malignant mixed
ryglands
Lymphoma malignant-histiocytic
Lymphoma malignant lymphacytic
Stomach
Stomach, forestomach
Stomach, glandular
.
Tooth
1
i-
x
+
+
5
5
5
5
2
E
4 "4
1
2
5
1
7
1
8
2
+
+
+
+
+
+
+
+
+
t
+
+
+
+
+n
+
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
.
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
+
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+
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+
+
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+
+
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+
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+
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+
.
+
i+
+
+
+
+
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-F
+
+
+
+
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i-
x
5
+
x
+
7{
t
+
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+
x
x
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
~-
+
+
+
+
+
a-
+
+
+
t
+
-F
+
+
i-
+
+
+
+
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+
+
i-
+
+
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. . .
+
+
t
.
+
+
+
+
+
a+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
t
+
+
+
+
Heart
Pericardium, lymphoma malignant
+
.
+
+
+
+
+
+
a-
+
+
+
+
+
+
+
.
+
+
-F-
+
+
+
+
+
Adrenal gland
Adrenal gland, cortex
Adrenal gland, medulla
Islets,
+
+
+
.
+
+
+
+
+
+
+
+
+
-r
+
+
+
+
+
+
+
+
+
ti-
+
+
+
+
+
+
t
+
-t-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
rii
+
+
+
+
+
+
M
+
+
NI
+
+
+
+
.
+
+
+
+
+
+
t
t-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
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+
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+
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t
+
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-I-h
+
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i+
+
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t
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M
+
+
+
+
+
.
+
+
+
+
X
M
+
+
+
M
+
ni5csocytic
pancreatic
Parathyroid gland.
,
,
t
Pituitary gland
Thyroid gland
Follicular ce11, adenoma
+
Seminal vesicle
Testes
Interstitial cell,adenoma
+
M +
Tissue, NOS
Coagulatingglaad
E pidid ymis
Preputial gland
Prostate
Lymphoma malignant mixed
,
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-F
+
+
+
+
-F
f
.
+
+
+
+
+
PA
+
+
+
+
+
+
+
+
+
t-
+
+
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+
.
+
+
+
+
+
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i-.
.
+
+
+
+
+
+
+
+
+
+
:
+
+
+
+
+
+
+
i-
+
+
.
+
+
+
+
+
+ + + . . .
+
-F +
+ + + + + . + + ++ ++ ++ +
+ + + + + + .x + + ++ . ++ ++ ++
,
X
+
+
183
Hydrocguinmne, IvTP `d'R 366
MALE MICE : HIGH DOSE
TABLE C2. INDIVIDUAL . ANIMAL TUMOR PATHOLOGY OF
(Continued)
i
wESxs ON
5
CARCASS
ID
Esopha~us
Ga
l
l4 ladder
Lymphoma malignant mixed
Intestine large
Intestine large, cecum
malignant
histiocytic
Lymphoma
Intestine large, colon
Intestine large, rectum
Serosa, carcinoid tumor benign
Intestine small
Intestine small, duodenum
Intestine small, ileum
. Lymphoma malignant lymphocytic
Jejunum, lymphoma malignant
lymphocytic
Intestine small, jejunum
Liver
Hemangioma
Hemangiosarwma
Hepatocellutar carcinoma
Hepat,ocellnlar adenoma
FYepatceellular adenoma, multiple
Lymphoma malignant histiocytic
Lymphoma malignant mixed
Mesentery
Lymphoma malignant histiocytic
Pancreas
Lymphoma malignant mixed
Salivary glands
Lymphoma ma lignant histiocytic
Lymphoma malignant lymphocytic
Sf,omach
Stomach, forestomach
Stomach, glandular .
Tooth
T M
Z`D-TONASL'YI AR
Heart
Pericardium, lymphoma malignant
histiocytic
Adrenal gland
Adrenal gland, cortex
Adrenal gland, medulla
Islets, pancreatic .
Parathyroid gland
Pituitary gland
Thyroid gland
Follicular cell, adenoma
i
i
5
5
5
S
4
1 1
o 0 0 0 0
~srvDY
.
5
°
T OTAL:
T ISSUES
T UMORS
8
3
9
Y
9
2
9
3
+
+
+
+
+
+
ii-
+
M
55
48
+
+
+
+
+
+
.
-
+
+
49
+
+
+
+
+
i-
-
+
+
+
-h
+
+
+
+
tf
+
+
+
4-
+
+
+
M
'{'
+
+
+
'}'
+
.
R
X
.
'
.
:
.
.
.
45
+
.
X
48
. 52
51
51
47
S1
2
,
X
.
15
5
5
+
+
+
+
+
+
~F
+
-~
+
1
_ 51
SS
+
+
+
X
+
M
+
+
+
+
+
+
+
.+
+
+
55
53
55
2
+
+
+
+
+
t
+
+
+
+
+
+
M
+
M
M
+
+
+
+
-t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
M
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+.
+
+
+
+
55
1
54
54
53
44
50
54
Tissue, NOS
Coagulating gland
Epididymis
Preputial gland
Prostate
Lymphoma malignant mixed
Seminal vesicle
Testes
Interstitial call, adenoma
Hydroquinone, NTPTR. 366
2
54
.
55
1
55
53
184
i
'.
.
TABLE C2. INDIVIDUAL ANIMAL TUMOR PATHOLOGY !7F MALE MICE : HIGH DOSE
(Continued)
WEEKS ON . .. STUDY
.
CARCASS
FIE
Hone marrow
Lymph node
Alveolar/bronchiolar carcinoma,
metastatic, lung
Iliac, lymphoma malignant mixed
Renal, lymphoma maligaaat lymphocytic
Thoracic, lymphoma malignant
histiocytic
Lymph node, =nandibnlar
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Lymph node, mesenteric
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic _
Spleen
:
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Thymus
Lymphoma malignant lymphocytic .
Mammary gland
Skin
Fibmsarcoma
.
Subcutaneous tiscue,fibrosarcoma
Subcutaneous tissue, hemangiosarcoma
Subcutaneous tissue, lymphoma
malignant lymphocytic
MUSCVLOSKELETAL SYSTEM
Bone
NERVOUS SYSTEM
Brain
Spinal cord
SPIRATORY SYSTEM
Lung
Alveolarlbronehiolaradenoma
Alveolartbronchiolar adenoma, multiple
Alveolar/bronchiolar carcinoma
HepatoceiSular carcinoma, metastatic,
liver
Lymphoma malignant bistiocytic
.
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Nose
Trachea
0
4
8
0
6
9
0
7
6
0
0
8 ` 8
2 ' 3
0
9
0
0
9
1
0
9
1
0
9
2
0
9
3
0
9
4
0
9
4
0
9
5
0
9
5
.0
3
3
0
9
8
0
9
8
0
9
9
1
0
0
1
0
5
1
0
5
11
1
1
0
0
0
0
5
5
5
5
-T-75
1
3
5 5
2
9
4
2
7
4
3
8
1
2
8
4
2
7
3
5
5
3
3
6
3
5
4
3
2
7
5
2
5
1
3
1
1
7
4
7
3
4
4
8
3
9
5
0
3
0
4
2
2
3 ~4
.
+
+
+
'r
+
+
+
+
+
+
+
+
+
.+
+
+
.
+
+
+
+
+
+
M-
+
+
+
t-
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
+
+
t
+
R
i-
M
+
+
X
+
X
+
A
+
+
+
+
t
+
+
+
t
.
t
NL
M
14Y
.,
+
M
+
+
+
M
+-
+
M
+
M
+
R3
i-
1YI
+
M
+
M
+
M
+
M
+
M
+
M
+
M
+
M
+
M
+
-F
i-
+
+
+
+ , +
+
+
+
t
+
+
+
t
+
+
+
+
+
+
+
i-
+
+
+
+
+
+
+
+
+
-h
+
+
+
+
+
-
.
g
+
X
+
.
+
+
f
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
M
+
+
+
+
.
+
+
+
+
'+' +
+
+
R
+
M
M
+
+
+
M
+
+
+
i
a-
+
M
ig
lYL
+
M
+
M
+
M
+
M
+
M
+
M
+
M
+
M
t
M
+
M
+
M
-tr-
+
+
+
+
+
i-
i-
P
-¢
.
.
t
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
+
+
+
+
+
+
+
+
+
+
+
g
+
+
+
+
X
g
-
g
g
X
7C
+
+
i-
i-
+
+
+
+
-F
+
+
+
+
t
+
+
+
+
SPECIAL SENSES SYSTEM
Eye
Hardarian gland
Adenoma
Lacrimal gland
URINARY SYSTEM
Kidney
Lymphoma
tubule,
malignant histiocytic
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
12eaat
carcinoma
Urethra
Urinary bladder
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
g
+
+
+
+
+
+
+
+
+
+
+
+
+
;{
+
%
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i~
t
+
+
+
+
i
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
185
Hydroquinone, NZ`P TR 366
WEEKS
STUDY
N
CARCASS
ID
Bone marrow
Lymph node
141veolarlbronchiolar carcinoma,
metastatic, lung
Iliac, lymphoma matignaat mined
Renal, lymphoma matignant Iymphocytic
Thoracic, lymphoma malignant
histiocytic
.,
Lymph node, mandibular
Lymphoma malignant histiocytic
Lymphomamalignant lymphocytic
Lymph node; mesenteric
Lymphoma malignant histiocytic
Lymphoma malignant lqmphocytic
Spleen '
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Thymus
Lymphoma malignant lymphocytio
TM
YSTEM
Mammary gland
Skin
Fibiosarcoma
Subcutaneous tissue, fibrosarcoma
Subcutaneous tissue, hemangiosarcoma
Subcutaneous tissue, lymphoma
malignant lymphocytic
Bone
A
Brain
Spinal cord
Lung
Alveolar/bronchiolar adenoma
Alveolarlbronchiolar adenoma, multiple
Alveolaribronchiolar carcinoma
Hepatocellular carcinoma, metastatic,
liver
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Nose
Trachea
Eye
Harderian gland
Adenoma
Lacrimal gland
1
4
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
4
5
1
0
5
1
0
5
.1
0
5
1
0
5
1
0
5
1
0 .
5
1
0
5
1
0
5
1
0
5
1
0
5
1
0
5
1
4
5
1
0
5
5
3
6
2
7
2
7
1
7
2
8
2
9
2
9
3
0
2
2
2
3
1
4
3
5
2
6
1
8
4
8
1
9
1
0
1
1
2
2
1
4
1
4
2
5
1
7
1
8
2
+
+
+
t
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.+
+
+
+
. .
+ +
M
+
.
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
M.
M
+
M
+
M
+
+
+
+
+
I-iydrcaquynmne, NTP TR 366
+
+
+
+
+
+
+
+
>
,
,
.
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
M M M M M
M
M
M
+
f
+
+
+
+
+
+
-h
+
+
+
t
+
+
+
t
+
+
+
+
+
M
M
+
+
+
+
+
+
+
+
~~
+
+
+
+
+,
-F
+
R
+
x
+
. ..
+
+
-r
M
. . .
+
+
-F
+
+
+
+
+
+
+
PJl
.
M
+
M
+
M
+
M
+
IvI
+
M
+
M
M Yvd
M
M
1VL
F
+
+
+
+
+
+
+
+
+
+
+
~h
+
+
+
+
+
+
+
+
.
+
+
'
+
+
+ . +
+
+
+
i-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
++
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
A
+
+
+
+
.
.
.
+
+
+
+
F
-
Kidney
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Renal
tubule, carcinoma
Urethra
Urinary bladder
+
.
+
+
.
+
+
+
+
+
+
+
x
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
i-
+
X
.
+
+
+
+
+
+
+
+
7(+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
x
+
+
+
+
+
+
+
186
,
+
h
+
+
+
+
+
.
+
+
+
+
+
TABLE C2. INDIVIDUAL ANIMAL `i°UIVBO It PATHOLOGY OF MALE MICE :
(Continued)
WEEK ON.
STUDY
1
0
5
1
0
5
I ~ -1 1
0
0
Q
5
5
5
CARCASS
ID
3
8
3
3
9
1
3
9
2
3
9
3
3
9
4
t
+
+
+
+
+
~+
+
-f+
ITEMATOPOIETIC SYSTEM
Bone marrow
Lymph node
Alveolar/bronchiolar carcinoma,
metastatic, lung
Iliac, lymphoma malignant mixed
Renal, lymphoma malig. lymphocytic
Thoracic, lymphoma malignant
histiocytic
Lymph node, mandibular
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Lymph node, mesenteric
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Spleen
Lymphoma malignant histiocytic
Lymphoma malignant lymphocytic
Thymus
Lymphoma malignant lymphocytic
INTEGUMENTARY SYSTEM
Mammary gland
Skin
Fibrosarcoma
Subcutaneous tissue, fibrosarcoma
Subcutaneous tissue, hemangiosarcoraa
Subcutaneous tissue,lymphoma
malignant lymphocytic
.
.
.
TOTAL:
TISSUES
TUMORS
.
55 .
55
.
+
+
+
+
+
+
.
+
+
.
+
+
+
+
.
+
X
+
+
M
M
M
+
M
+
M
+
M
+
M
+
X
.
¢
+
X
HIGH DOSE
-
51
L
.
,
50
.
-
3
54
qg
Y
55
.
X
.
.
.
X
Bone
+
+
+
+
+
55
NERVOUS SYSTEM
Brain
+
+
+
+
r
55
Lung
Alveolarlbronchiolar adenoma
Aiveolarlbronchiolar adenoma, multiple
Alveolarlbronchiolarcarci¢oma
Hepatocellular carcinoma, metastatic,
liver
Lymphoma malignant histiocytic
+
+
+
+
+
Nose
Trachea
+
+
Spinal cord
TORY 9YSTZM
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
+
g
55
g
-
X
.
g
$
g
%
+
+
+
+
+
+
+
+
SS
55
SPECIAL SENSES SYSTEM
FTarderian gland
Fideeoma
Lacrimal gland
URINARY SYSTEM
Kidney
Lymphoma malignant histiocytic
+
Lymphoma malignant lymphocytic
Lymphoma malignant mixed
Renal tubule, carcinoma
Urethra
Urinary bladder
7
g
+
R
+
.
+
+
-
+
X
55
7,
.
.
+
+
+
+
+
.
187
-
2
55
Hyclraquinone, NTP'TR 366
TABLE C3.
°
TWO-YEAR BaAVE1GE STUDY OF
ANALYSIS OF PRIMARY TUMORS IN MALE MICE IN THE
kYYDROQiY .TINONE
Vehicle Control
50 mg/kg
100 mg/kg
Adrenal Medulla: Plaeochromocytoxna
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Coc4sran-Armitage Trend Test (d)
Fisher Exact Test (d)
1/54(2%)
2. 6%
0/32(0%)
691
P=0 . 359N
P=0.36&N
P=0 .379N
3/52(6%)
8 .3%
3/36(8%)
729
P=0 .341
P=0.31i
0/64(0%)
0 .0%
0/35(0%)
I'=0295
P=0 .5UOP3
Harderian Gland : Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day off First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochean-Armitage Trend Test (d)
Fisher Exact Test (d)
5/55(9%) ,
12 .6%
2/33(6%)
635
P=0 .470
P=0 .447
P=U .430
2154(4Wo)
5 .4%
2137 (5°~aJ
729
P=0 .192N
P=0220Dd
6/55(11%)
15 .8%
5/36(14.%)
649
P=0 .544
P=0 .518
P=0. 226Pd
P=0.500
Liver: Hepataceilular Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
9/56(16%)
25 .5°l0
7/33(21%)
694
P=0 . 025
P=0 .018
P=0 .015
21/64 (39°l0) .
49 .3 %
16/37(43%)
441
P=0,022
P=0 .fl08
20156(36%)
51 .1%
17/36(47%)
661
P=0 .025
P=0 .OI5
P=t}.007
P=fl .015
Liver: 1lepatoceliulas Carcinoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates tcl
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
13/55(24%)
23 .6°Io
5/33(15%)
539
P=0.088N
P=0 .094N
P=0 .090N
14/54(20%)
24.$9'o
5/37 (14%)
465
P=0 .3&'1N
P=(3 .430N
7/55(13%)
16 .9%
4136(11%)
526
P=0 .106N
P=0 .i14N
P=C+ . 423N
P=0 .1O8P1
20/55(36%)
462%
11/33(33%)
537
P=0299
P=0223
P=0 .194
29/54(54%)
64 .1%
21/37 (57%)
441
P=0.151
P=0 .053
25/55(45%)
59 .0%
19/36(53%)
526
P=0.317
P=0250
P=0 . 052
P=0 .219
.
.
!
.
.
Liver- Fiepatocellulat Adenoma or Carcinoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cachran-Armitage Trend Test (d)
Fisher Exact Test (d)
!
I'
G
Lung- Alveolar/Bronchiolar Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
I:
f
Hydroquinone, NTP'I'R 366
6/55(11%)
182%
6/33(18%)
729
(e) 9131 (29%)
P=0 .505N
P=0 .498N
4/55(7%)
11 .1%
4/36(11%)
729
P=0 .313N
P=0 .323N
P=0 .371IV
Vehicle Control
Lung: Alveolar/Bronchiolar Carcinoma
'
'
'
,
' Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
8/55(16%)
21 .1%
4/33(12%)
649
Lung: Alveolar/Bronchiolar Adenoma or Carcinoma
Overall Rates (a)
14/65(25%)
Adjusted,Rates (b)
37.49'0
Terminal Rates (c)
10/33(30%)
Day of First Observation
649
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
Pituitary Gland/Pass Distalis : Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
"
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
Tneegaarnetatax°y System: Fflbrorna
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test td?
3l60 (6%)
9 .3%
2/30(7%)
701
2/55(4%)
6.1%
2/33 (6%)
729
P=0 .185N
P=0 .193N
P=0203IV
Integumentary System- Fibrosarcoma
Overall Rates (s)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
100 mg/kg
(e) 4/31 (13%)
6/55(11%)
14.7%
3/36(8%)
563
P=0 .3b4N
F'=0 .370N
P=0 .388N
(e) 11/31(35%)
10/55(18%)
25.0%a
7/36(19%)
563
E'=4 .1972V
P=0 .213N
P=C3 .245N
-
(e) 0114 (0%)
0/50(0%)
0 :0%
0/31(0%)
P=0.117N
P=0 .120IV
P=0 .121N
3/54(6%)
7.?%
2/37(5%)
&62
I'=0.539
P=0 .507
0/55(0%)
0 .0%a
0/36(0%)
F'=0 .491
F'=0 .248N
3/55(5%)
9 .1°la
3/33(9%)
729
P=0.0$8N
P=0.094I3
P=0.102N
3/54(6%)
7 .7%
2/37(6%)
662
P=Q.620RT
P=0.654N
0/55(0%)
0 .0%a
0/36(0%)
P=0.652
P=0 .122N
7/55(13%)
16 .3%
1/33(3%)
635
P=0 .144N
P=01451V
P=0 .149N
9/54(17%)
20 .9%
4/37(11%)
596
P=0 .441
P=dD .380
3/55(5%)
7 .3%
2/36(6%)
661
P=4.260N
P=0.158N
P=0 .378
P=Q .160N
I11tegYYmeri$i.LY°y System: 1'EbCORta Or N0Y7g°i3$EbCOri19,
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
50 mg/kg
189
P=(3.219N
P=0219N
P=0 .106N
P=0 .106IV
fIyrdroquinone, NTP TR 366
TWO-YEAR 6sAVAGE STUDY OF
TABLE C3. ANALYSIS OF PRIMARY TUMORS IN MALE MICE IN' THE
HYI9ROQTJINORIE (Continued)
Vehicle Control
Integumentary System : Filsroma or F'sbrosarcoma
9/5506%)
Overall Rates (s)
21 .6%
Adjusted Rates (b)
3/33(9%)
Terminal Rates (c)
635
Day of First Observation
P=0 .060Id
Life Table Tests (d)
P=0 .05$N
Logistic Regression Tests (d)
P=0.062N
Coctaran-Armitage Trend Test (d)
Fisher Exact Test (d)
Integumentary System: Sarcoma or &"ibrasarcoma
8/55 (15%)
Overall Rates (s)
18 .4°la
Adjusted Rates (b)
1/33(3%)
Terminal Rates (e)
635
Day offFirst Observation
F'=0 .1Q5N
Life Table Tests (d)
P=0 .102PT
Logistic Regression Tests (d)
P=o~ydgN
Coehran-Armfitage Trend Test (d)
Fisher Exact Test (d)
inPegaameeetary System: Filbropaxa, NeurofibroraYa9
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
,
'
'
I-
Testis: Interstitial Cell Adenoma
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Jay of First Observation
Life Table Test (d)
Logistic Regression Test (d)
Fisher Exact Test (d)
Circulatory System : Iiemangiosarcoaraa
Overall Rates (a)
Adjusted Rates (b)
Terminal Rates (c)
Day of First Observation
Life Table Tests (d)
Logistic Regression Tests (d)
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
50 mglkg
100 mgllsg
10/54(19%)
23 .3~°0
5/37(14%) '
596
IP=Q .555
P=0 .487
3/55(5%)
7 .8%
2/36(6%) . .
664
F=0 .064N
P=0 .U60N
P=0 .482
P=0 .062N
12/54(22%)
28 .19'0
7/37(19%)
596
P=0 .281
P=0 .2fl8
3/55(50/0
7 .8%
2/36(6%)
661
F'=0 .107N
F'=0 .100
P=O.2flS
P=0 .lO1N
Sarcoma, or Fibrosarcoana
11/55 (20%)
13/54(24%)
30 .6'l0
26 .1°Io
8/37(22%)
4/3302%)
635
596
P=0 .485
P=0 .02&N
P=0 .398
P=0 .024N
.027N
1'=0
P=0 .389
1155(2%)
2 .6%
0/33(0%)
691
1/55(2%)
3 .0%
1/33(3%)
729
P=0.222
P=0.211
P = 0.203
Circulatory System : Heuaangeoma or Fiemangiosareoma
2/55(4%)
Overall Rates (a)
5 .0%
Adjusted Rates (b) .
1133(3%)
Terminal Rates (e)
604
Day of First Observation
F'=0 .261
Life Table Tests (d)
P=0 .243
Logistic Regression Tests (d)
P=0 .240
Cochran-Armitage Trend Test (d)
Fisher Exact Test (d)
(e) 0/18 (09'0)
3/55(5%)
7 .8°l0
2/36(6%)
661
P=(3.025N
P=0 .021N
P=0A21N
3/55(6%)
8 .3%
3/36(8%)
729
P=0 .328
P=0.318
P=0.309
1/54(2%)
2 .79'0
1/37 (3%)
729
P=0.736N
P=0.73&N
3/55(5%)
7.7%
2/36(6%)
655
P=0 .334
P=0 .316
P=0 .748
P=0 .309
1/54(2%)
2 .7%
1/37(3%)
729
P=0 .478N
P=Q.505N
4/55(7%)
9 .9~'0
2/36(6%)
655
P=0 .365
P=0 .337
P=0.5071V
F=0 .339
TABLE C3. ANALYSIS OF PRIMARY TUMORS IN MALE MICE
IN THE TWO-YEAR GAVAGE STUDY OF
fI'YDR04LTII+IeBNE (Continued)
Vehicle Control
Hematopoietic System: Lymphoma, All Malignant
Overall Rates (a)
6/a5(11%)
Adjusted Rates fb3
15.2%
Terminal Rates (c)
3/33 (9%) :
Day of First Observation
330
Life Table Tests (d) .
P=0 .493
Logistic Regression Teats (d)
P=0 . 436
Cochsan-Armitage Trend Test (d)
P=0 .446
Fisher Exact Test (d)
50 mg/kg .
100 mg/kg
21/S4 (20%)
26.3%
7/37(19%)
64$
P=0203
P=0.137
7/55 (139b)
i7 .19~0
5/36(14%)
330P=U.548
P=0 .446
P=U,i36
P=0 .500
(a) Number oftumor-bearing animals/number of animals examined at the site
(b) i{aplan-Meier estimated tumor incidences at the end of the study
after adjusting for flntetcurrent mortality
(c) Observed tumor incidence at terminal kill
(d) Beneath the vehicle control incidence are the P values associated with the trend
test . Beneath the closed group incidence are
the P values corresponding to pairwise comparisons between that dosed group
and the vehicle controls. The life table analysis
regards tumors in animals dying prior to terminal kill as being (directly or indirectly)
the cause of death. The logistic regression test regards these lesions as nonfatal . The Cochran-Armitage and Fisher
rates . A negative trend or lower incidence in a dosed group is indicated by (IV). exact tests compare directly the overall incidence
(e) Incomplete sampling oftissues
191
Hydroquanone, NTP TR 366
TABLE C4 . HISTORICAL INCIDENCE OF HEI'A'fl'OCEI.LIIE .r1R TUMORS IN MALE B6C3F1 MICE (a)
Study
Adenoma
Incidence nn Controls
Carcinoma
Adenoma or
Carcinoma
Historical Incidence for All Water Gavage Vehicle Controls
dodinateai.glygerol (b)
Chdorphesoiramine maleate (c)
Tetrakis(Iaydrogymethyl)phosphonium chloride (c)
1VIaloraaldetayde, sodium salt (c)
Tetrakis(hydroxymethyl)phasphonium sulfate (c)
Methyl csrbamate (d)
Chlorinated trisodium phosphate (b)
"
TOTAL
SD (e)
8l50
10/50
8449
4l50
9048
9/50
6/50
54/347 (15 .6R'o)
4.21%,
Range (f)
High
Low
10150
4/50
2/50
fi15t1
10149
14/50
10148
5/5d
9l50
56J347 (16 .1%a)
8 .03%
14150
2/54
Ip/5p
16/50
17/49
17/50
18J48
14/50
14150
-
106/347 (30 .5°k)
5 .83%
18/48(38%)
10/50
Overall Historical Incidence for Untreated Controls
TOTAL
5I3 fe9
Range (f)
High
Low
259/2,032 (12 .7%)
7 .21%
22/50
0149
379/2,032(1$ .7%)
6 .50%
15/50
4/50
609/2,032 (30 .0%)
7 .59%
!
29/50(58%)
8150
(a) Data as ofApril 29,1987y for studies of at least 104 weeks
(b) Study performed at EG&G Mason Research Institute
(c) Study performed at BsttelIe Columbus Laboratories
(d) Study performed at Microbiological Associates
(e) Standard deviation
(f) Range and SD are presented for groups of 34 or more animals .
'
I
i
i
i
ydroqttinone,NTP Tgt 366
192
TABLE c5. SUMMARY OF THE INCIDENCE OF NoxxEoPr.ASZZC LESIONS IN MALE MICE IN THE
TWO-YEAR GavAGE STUDY OF HYDROQUINONE
Vehicle Control
Animals initially in study
Animals removed
Animals examined histopathologicmlly
t
;
L
?
;
;
;
i
I
;
ALIMENTARY SYSTEM
Gallbladder
Inflammation, chronic
Intestine small, ileum
Amyloid deposition
Mucoss, necrosis
Peyer's patch, hyperplasia ; lymphoid.'
Intestine small,jejunum
Diverticulum
Hyperplasia, lymphoid
Ivlucosa, inflammation, suppurative
Liver
Amyloid deposition
Anisokaryosis
tlut.oiysis
Basophilic focus
Clear cell focus
cyst
Cytomegaly
Eosirnophilic focus
Fatty change
Focal cellular change
F-¬ematopoietic cell proliferation
Hypetplasia, lymphoid
Hyperptasia, re cell
Infarct
Inflammation, chronic
Mixed cell focus
Necrosis
Necrosis,focal
Syncytia! alteration
Thrombus
Centrilobular, degeneration, ballooning
Sinusoid, dilatation, focal
Mesentery
Hemorrhage
Inflammation, acute
j
Inflammation, chronic
Inflammation, suppurative
Fat, inflammation, chronic
Fat, necrosis, focal
Pancreas
Fibrosis, focal
Hemorrhage, focal
Inflammation, chronic
Acinus, vacuolization cytoplasmic
Serosa, inflammation, acute
Salivary glands
Concretion, chronic
Degeneration, chronic
Inflammation, chronic
Stomach, foresf,omach
Acaxnthosis
Ulcer
Stomach, glandular
Ulcer
Low Dose
65
65
55
' 65
65
54
(44)
(11)
(48)
1 (2~'0)
(10)
(50)
d13)
1 (8qo)
65
65
55
(48)
1 (2°l0)
(47) . : ,
L (2%)
~ 1 (2%)
(45)
i (29'o)
i ($%)
4543
(5b)
I (23'0)
2
1
5
2
1
2 (4'Yo)
3 (6%)
2 (49'0)
1 (2%)
1 (29'a)
2
4
1
5
1
High Dose
(4%)
(7%a)
(2%)
(9%)
(2%)
(6)
1 (17%)
1 (17~'0)
3 (50%)
(54)
1 (2°l0)
1 (2%)
(5b)
1 (2%)
12 (22%)
, (49'0)
(2%)
(99'0)
(4%)
(2%)
14 (204'0)
4
1 (2qo)
1 (29'0)
1 (2°10)
2 (4%)
1 (25%)
1 (25%)
{15)
(16)
1 (2%)
30 (553'0)
(55)
$ (509'0)
(15)
193
1
1
1
1
2
(2%)
(29'0)
(2%)
(2g'o)
(4g'o)
1 (2%)
1 (2%)
(b)
(4)
(15)
(29'0)
(b%)
(7%)
(5%)
25 (45Wo)
3 (6%)
(65)
(55)
1 (2%)
1
3
4
3
1 (20%a)
1 (20%)
1 (203'0)
1 (203b)
(53)
2
1
1
(55)
1
(4%)
(29'0)
(2%)
31
(53)
1
1
(55)
1
(56%) .
(2%)
(2%)
(2%)
(2%)
Hydroquinone, NTP TR, 366
,
TABLE C5 . SUMMARY OF THE INCII3ENCE OF NONNEOPLAS'I'tC LESIONS IN MALE MICE IN THE
TWO-YEAR GA'VAGE STUDY OF HYff21ZOQi7YNONE (Continued)
Vehicle Control
ALIMENTARY SYSTEM (Continued)
Tooth
1'ericlon4,afl tissue, inflammation, suppuratiae
Peridoretai tissue, pulp, abscess
Pulp, abscess
Pulp, necrosis
CARDIOVASCULAR SYSTEM
Heart
Cardiomyop.athY
Inflammation, acute
Inflammation, chronic
Atrium left, thrombus
ENDOCRINE SYSTEM
Adrenal gland
Subcspsular, hyperpiasia
Adrenal gland, cortex
Degeneration, focal
Ectopic tissue
TiyperpIasia,focal
Hypertrophy, focal
Spindle cell, subcapsuIar, proliferation
Adrenal gland, medulla
I-Fyperpiasia, focal
Pituitary gland
Pars distaiis, hyperplasia, focal
Thyroid gland
Inflammation, chronic
Inflammation, suppurative
Follicle, cyst, multiple
Follicle, inflammation, acute
Follicular cell, hyperplasia
(6)
2
1
2
1
Low Dose
(1)
(3396)
(1?%)
(339'a)
(17%)
1 (i009b)
(56)
(17)
Y (2%a)
1 (2%)
(55)
1
(55)
5
1
9
~
1 (6%)
'
-
High Dose
(2)
1 (50%)
1 (50%)
(55)
1 (2%)
1 (2S'o)
(2%)
(9%)
(2%)
(1&9b)
(53)
(64)
(52)
2 (2%)
(54)
2 (4%)
1 (23'0)
1 (2%)
(52)
3 (6%)
(14)
1 (7%)
(53)
(54)
1 (2%)
(60)
3 (6%)
(55)
2 (2%a)
1 (29'0)
f (2~'0)
5 (9%)
15 (BII%)
6 (11%)
1 (23'o)
(54)
1 (29°0)
(50)
5 (10%)
(54)
2 (4%)
1 (2%)
19 (35%)
GENERAL BODY SYSTEM
None
GENITAL SYSTEM
Epididymis
Inflammation, chronic
Preputial gland
Inflammation, chronic
Inflammation, suppurative
Duct, ectasia
Prostate
Inflammation, acute
Inflammation, chronic
Inflammation, chronic active
Inflammation, suppuraCive
Serosa, inflammation, acute
Seminal vesicle
Dilatation
Inflammation, chronic
Inflammation, suppurative
Serosa, inflammation, acute
Testes
Atrophy
Germinal epithelium, degeneration
Hydsoquinone,NTP TR 366
(54=)
1 (2%)
1)
5 (45%)
(17)
(9)
3 (33%)
(54)
3 (6%)
(7)
2 (29%)
2 (9%)
(55)
1 (il%)
(17)
1 (14%)
(55)
5 (45%)
6 (11~'0)
3 (5%)
1 (2%)
(55)
1 (2%)
2 (4%)
1 (2%)
(58)
2 (4%)
194
6 (67%)
1 (6%)
.
1 (6C/o)
(17)
(18)
4 (57%)
Y (2%)
9 (16%)
1 (2%)
(55)
1 (2%)
(55)
1 (2%a)
p (2~'0)
a
.
TABLE C5. SUMMARY OF THE INCIDENCE OF iV01mT101EOPLAS'II°IC LESIONS TN MALE MICE IN THE
TWO-YEAR GA9'AGE STUDY OF HYDROQUINONE (Continued)
Vehicle Control
EiEMATOPOIETIC SYSTEM
Lymph node
Congestion
Hyperplasia, lymphoid
Hyperplasia, lymphoid, plasma cell
Hyperplasia, plasma cell
Inflammation, acute
Axillary, hqperplasia, lymphoid
Axillary, hyperpIasia, plasma cell
Iliac, hematopoietic cell proliferation
Iliac, hyperplasia
Iliac, hyperplasim, lymphoid
Iliac, hyperplasia, plasma cell
Inguinat, cyst
dnguinal, tnyperptasia, lymphoid
Lumbar, congestion
Lumbar, hyperplasia, lymphoid
Mediastinal, hyperplasis
Pancreatic, congestion
Popliteal, hyperplasia, lymphoid
Papliteal, hyperplasia, plasma cell
Renal, hyperplasia, lymphoid
Renal, hyperplasia, plasma cell
Lymph node, mandibular
Congestion
Hyperplasia, lymphoid
Hyperplasia, plasma cell
Lymph node, mesenteric
Congestion
Hematopoietic cell proliferation
Hyperplasia, lymphoid
Inflammation, acute
Spleen
Arn3rloid deposition
Priernatopoieticcell proliferation
Hyperplasia, lymphoid
Thymus
Amylaid deposition
(55)
(29)
1 (3%)
1 (296)
1 (2%)
i (2%a)
1 (23'0)
fl (23'o)
1 (2%)
1
1
1
1
1
i
4
1
(52)
2
!
Low Dose
(23'0)
(2%)
(2°10)
(2%)
(29'0)
(29b)
(2%)
(2%)
1 (390)
I (395)
1 (3%)
1 (3%)
High Dose
(55)
1,(2%)
1 (2%)
1 (29'0)
`
1 (39'0)
1 (39b)
(Y7)
(51)
(54)
11 (20%)
fl (2%)
(23)
6 (26%)
4 (4%)
5 (10%)
(50)
10 (20R'o)
1 (29'0)
1 (2%)
(55)
t52)
(4%)
(2%)
3 (6%)
10 (18%)
(39)
14 (2790)
d10)
INTEGUMENTARY SYSTEM
Skin
(55)
Acanthosis
2 (4%)
Alopecia
2 (4%)
Atrophy
I (23b)
Inflammation, chronic
Ulcer
5 (9%)
Artery, subcutaneous tissue, inflammation,
1 (2%)
chronic
1 (2°h)
Dermis, fibrosis
1 (2%)
F3erreais, inflammation, chronic
Dermis, dorsal, atrophy
2 (4%)
Prepuce, inflammation, chronic
Prepuce, inflammation ; suppuratiee
2 (4%)
Subcutaneous tissue, edema
1 (2%)
Subcutaneous tissue, hemorrhage
i (2Wo)
Subcutaneous tissue, inflammation, chronic
Subcutaneous tissue, inflammation, subacute
1 (2%)
1 (2%)
Subcutaneous tissue, inflammation, suppurative
Tail, dermis, inflammation
195
(33)
3 (9%)
3 (9%)
1 (3%)
6 (18%)
1 (33'a)
(b4)
1
6
2
(42)
1
(5b)
2
1
1
2
14
(2%)
(11%)
(4~'0)
(29'0)
.
(4%)
(2%)
(2%)
(4%)
(253b)
2 (4%)
1 (2%)
1 (3%)
1 (2%),
I (3%)
1 (2%)
Hydroquinone, NTP TR, 366
TABLE c5. SUMMARY OF THE INCIDENCE OF NoNraEOPLASTIc LESIONS IN MALE MICE IN THE
TWO-YEAR GAVAGE STUDY OF xYDtaoQuixoNE (Continued)
Vehicle Control
MUSCULOSKELETAL SYSTEM
Bone
Fiyperostosis
Joint, tarsal,hyperostasis
Skeletal muscle
Abdominal, fibrosis
(54)
10 (f9%)
(3)
1 (33%)
NERVOUS SYSTEM
Brain
Cyst epithelial inclusion
Mineralization
(55)
RESPIRATORY SYSTEM
Lung
Congestion
(55)
2 (49'0)
Hemorrhage
Alveolar epithelium, hyperplasia
Alveolar epithelium, hyperplasia, atypical
Alveolus, hYperplasia, macrophage
Vein, Ieukocytosis
Nose
Lumen, turbinate, inflammation, suppurative
Nfucosa, inflammation, chronic
Nasolacrimal duct, inflammation, chronic
1 (2%)
(65)
2 (4%)
Museularis, hemorrhage
Pexivascular, inflammation, chronic
Submucose, inflammation, chronic
Wall, inflammation, subacute
Hydroqtsinone;lV7'P TR 366
(55)
(17)
1 (sqb)
(55)
(31)
4 (13%)
(55)
1
1
P.
I
(17)
t3%3
(3qv)
(3%)
(3R'o)
(17)
2 f4°.'o?
1 (2~'0)
3
45
I
1
4
(b%)
(82%)
(2%)
(2g'o)
(2%)
1 (6%)
11 (65go)
1 (6%)
1 (6%)
i (23"0)
2 (4%)
(55)
1 (2%)
(1)
g (ipoq+a)
(55)
1 (2%)
p (Zcqo)
44 (80%)
1 (2%)
(2)1 (50°90)
1 (33%)
2 (4%)
15 (283'0)
1 (23b)
a cz%>
2 (4%)
(3)
2 (67~'0)
(b4)
7 (13%)
3 (5%)
(1)
(b5)
High Dose
(32)
5 (I6%)
30 (32°Io)
2 (4qo)
SPECIAL SENSES SYSTEM
I,acrirnai gland
Extraorbitalninflamenation,chronic
URINARY SYSTEM
Kidney
Amyloid deposition
Calculus micro observation only
Cyst, multiple
CyLoplasmic alteration
Glomerailosclerosis
Inflammation, chronic
Inflammation, suppurative
Nephropathy
Cortex, infarct
Renal tubule, mineralization
Urethra
Distal, concretion
Distal, inflammation, chronic
Distal, inflammation, suppurative
Proximal, inflammation, suppurative
Urinary bladder
Low Dose
(15)
2 (13~'0)
1 (50%)
1 (50%)
(b5)
1 (2%)
13 (24%)
196
.