toxicology and carcinogenesis studies of ... · toxicology and carcinogenesis studies of...
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Toxicology and carcinogenesis studies of tetrachloroethylene in F344/DuCrj rats and
Crj:BDFl mice (two-year inhalation studies)
Study No.0104; F344/DuCrj rats
Study No.0105; Crj:BDFl mice
Table 1: Experimental design and materials and methods in the 2-year inhalation study
of tetrachloroethylene.
TablelO : Survival animal numbers and body weight changes in male rat (two-year
studies)
Tablell : Survival animal numbers and body weight changes in female rat (two-year
studies)
Tablel4 : Food consumption in male rat (two-year studies)
Table15 : Food consumption in female rat (two-year studies)
Table29 : Survival animal numbers and body weight changes in male mouse (two-year
studies)
Table30: Survival animal numbers and body weight changes in female mouse (two-year
studies)
Table33 : Food consumption in male mouse (two-year studies)
Table34 : Food consumption in female mouse appendix
Appendix Ll : Histological Findings: non-neoplastic lesions (two-year studies:
summary), rat: male: dead and moribund animals
Appendix L2 : Histological Findings: non-neoplastic lesions (two-year studies:
summary), rat: female: dead and moribund animals
Appendix L3 : Histological Findings: non-neoplastic lesions (two-year studies:
summary), rat: male: sacrificed animals
Appendix L4 : Histological Findings: non-neoplastic lesions (two-year studies:
summary), rat: female: sacrificed animals
Appendix L5 : Histological Findings: non-neoplastic lesions (two-year studies:
summary), mouse: male: dead and moribund animals
Appendix L6 : Histological Findings: non-neoplastic lesions (two-year studies:
summary), mouse: female: dead and moribund animals
Appendix L7 : Histological Findings: non-neoplastic lesions (two-year studies:
summary), mouse: male: sacrificed animals
Appendix L8 : Histological Findings: non-neoplastic lesions (two-year studies:
summary), mouse: female: sacrificed animals
Appendix Nl : Number of animals with tumors and number of tumors- time related,
rat: male
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Appendix N2 : Number of animals with tumors and number of tumors - time related,
rat: female
Appendix N3 : Number of animals with tumors and number of tumors- time related,
mouse: male
Appendix N4 : Number of animals with tumors and number of tumors - time related,
mouse: female
Appendix 01 : Neoplastic lesions- incidence and time of tumor occurrence, rat: male
Appendix 02 : Neoplastic lesions- incidence and time of tumor occurrence, rat: female
Appendix 03: Neoplastic lesions- incidence and time of tumor occurrence, mouse: male
Appendix 04 : Neoplastic lesions - incidence and time of tumor occurrence, mouse:
female
Appendix Pl : Neoplastic lesions- incidence and statistical analysis, rat: male
Appendix P2 : Neoplastic lesions- incidence and statistical analysis, rat: female
Appendix P3 : Neoplastic lesions - incidence and statistical analysis, mouse: male
Appendix P4 : Neoplastic lesions- incidence and statistical analysis, mouse: female
Appendix Ql : Identity and purity of tetrachloroethylene performed at the Japan
Bioassay Laboratory(two-year studies)
Appendix Q2 : Stability of tetrachloroethylene at the Japan Bioassay Laboratory(two
year studies)
Appendix Rl : Concentration of tetrachloroethylene in inhalation chamber(two-year
studies)
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(Study No 0 104)
TABLE 1 EXPERIMENTAL DESIGN AND MATERIALS AND METHODS IN THE 2-YEAR INHALATION STUDY OF TETRACHLOROETHYLENE
Inhalation
Male 4, Female 4
50 males and 50 females of each group
Strain and Species
F344/DuCrj(Fischer)rat Animal Source
Charles River Japan, Inc Duration Held Before Study
2wk Age When Placed on Study
6wk Age When Killed
no~1n wk
Male and Female 0, 50, 200 or 600ppm
6 hid, 5 d/wk for 104 wk
Feed
CRF-1 (Oriental Yeast Co., Ltd) Sterilized by y -ray Available ad libitum
Water Filtrated and sterilized by ultraviolet ray Automatic watering system Available ad libitum
Animal per Cage Single (stainless steel wire)
Animal Room Environment Barrier system Temperature : 242'C Fluorescent light : 12 hid Air changes : 15~17 time/h
Chamber Environment Barrier system Temperature : 242'C Humidity : 5510% Air changes : 9 time/h Pressure : o~-15mmAq
Clinical Sign
Observed 1 per day for mortality, Detailed clinical observation performed on
once weekly before exposure Body Weight
Weighed 1 per wk for 14wk Weighed 1 per 4wks thereafter and 104wk
Food Consumption Weighed 1 per wk for 14wk Weighed 1 per 4wks thereafter and 104wk
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(Study No 0 104)
TABLE 1 EXPERIMENTAL DESIGN AND MATERIALS AND METHODS (Continued) IN THE 2-YEAR INHALATION STUDY OF TETRACHLOROETHYLENE
Urinalysis performed on all animals that survived to end of dosing period using fresh urine collection.
The following measurement parameters were examined; pH, Protein, Glucose, Ketone body, Bilirubin, Occult blood, Urobilinogen
Hematological examination performed on scheduled sacrificed animals. The following measurement parameters were examined;
Red blood cell (RBC), Hemoglobin, Hematocrit,
Mean Corpuscular Volume (MCV),
Mean Corpuscular hemoglobin (MCH),
Mean Corpuscular hemoglobin concentrate (MCHC),
Platelet, White blood cell (WBC), Differential WBC.
Biochemistrical examination performed on scheduled sacrificed animals The following measurement parameters were examined;
Total protein, Albumin, NG ratio,
Total bilirubin, Glucose, Total cholesterol, Triglyceride, Phospholipid,
Glutamic oxaloacetic transaminase (GOT),
Glutamic pyruvic transaminase (GPT),
Lactate dehydrogenase (LDH),
Alkaline phosphatase (ALP),
y -Glutamyl transpeptidase ( y -GTP),
Creatine phosphokinase (CPK),
Urea nitrogen, Creatinine, Sodium, Potassium, Chloride,
Calcium, Inorganic phosphorus
Necropsy performed on all animals
Organ weight measurement performed on scheduled sacrificed animals. The following organs were weighed;
adrenal, testis, ovary, heart, lung, kidney, spleen, liver, brain
Histopathologic examination performed on all animals
The following organs were examined;
skin, nasal cavity, nasopharynx, larynx, trachea, lung,
bone marrow, lymph node, thymus, spleen, heart, tongue,
salivary gland, esophagus, stomach, small intestine,
large intestine, liver, pancreas, kidney, urinary bladder,
pituitary, thyroid, parathyroid, adrenal, testis, epididymis, seminal vesicle,
prostate, ovary, uterus, vagina, mammary gland,
brain, spinal cord, peripheral nerve, eye, Harderian gland, muscle, bone,
other organs/tissues with gross lesions.
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(Study No. 0105)
TABLE 1 EXPERIMENTAL DESIGN AND MATERIALS AND METHODS IN THE 2-YEAR INHALATION STUDY OF TETRACHLOROETHYLENE
Inhalation
Male 4, Female 4
50 males and 50 females of each g:rottp
Strain and Species
Crj:BDF 1 mouse Animal Source
Charles River Japan, Inc Duration Held Before Study
2wk Age When Placed on Study
6wk Age When Killed
ll0~1ll wk
Male and Female 0, 10, 50 or 250ppm
6h/d, 5d/wk, for 104wk
Feed
CRF-1 (Oriental Yeast Co, Ltd.) Sterilized by y -ray Available ad libitum
Water Filtrated and sterilized by ultraviolet ray Automatic watering system Available ad libitum
Animal per Cage Single (stainless steel wire)
Animal Room Environment Barrier system Temperature : 242"C Fluorescent light : 12hld Air changes : 15~ 17 timelh
Chamber Environment Barrier system Temperature : 242"C Humidity : 5510% Air changes : 9 time!h Pressure : o~-15mmAq
Clinical Sign
Observed 1 per day for mortality, Detailed clinical observation performed on
once weekly before exposure.
Body Weight Weighed 1 per wk for 14wk Weighed 1 per 4wks thereafter and 104wk
Food Consumption Weighed 1 per wk for 14wk Weighed 1 per 4wks thereafter and 104wk
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(Study No. 0105)
TABLE 1 EXPERIMENTAL DESIGN AND MATERIALS AND METHODS (continued) IN THE 2-YEAR INHALATION STUDY OF TETRACHLOROETHYLENE
Urinalysis performed on all animals that survived to end of dosing period using fresh urine collection. The following measurement parameters were examined;
pH, Protein, Glucose, Ketone body, Occult blood, Urobilinogen.
Hematological examination performed on scheduled sacrificed animals The following measurement parameters were examined;
Red blood cell (RBC), Hemoglobin, Hematocrit,
Mean Corpuscular Volume (MCV),
Mean Corpuscular hemoglobin (MCH),
Mean Corpuscular hemoglobin concentrate (MCHC),
Platelet, White blood cell (WBC),
Differential WBC
Biochemistrical examination performed on scheduled sacrificed animals. The following measurement parameters were examined;
Total protein, Albumin, A/G ratio,
Total bilirubin, Glucose, Total cholesterol, Triglyceride,
Glutamic oxaloacetic transaminase (GOT),
Glutamic pyruvic transaminase (GPT),
Lactate dehydrogenase (LDH),
Alkaline phosphatase (ALP),
Creatine phosphokinase (CPK),
Urea nitrogen, Sodium, Potassium, Chloride,
Calcium, Inorganic phosphorus ..
Necropsy performed on all animals ..
Organ weight measurement performed on scheduled sacrificed animals .. The following organs were weighed;
adrenal, testis, ovary, heart, lung, kidney, spleen, liver, brain
Histopathologic examination performed on all animals
The following organs were examined;
skin, nasal cavity, nasopharynx, larynx, trachea, lung, bone marrow,
lymph node, thymus, spleen, heart, tongue, salivary gland, esophagus,
stomach, small intestine, large intestine, liver,gall bladder, pancreas,
kidney, urinary bladder, pituitary, thyroid, parathyroid, adrenal, testis,
epididymis, seminal vesicle, prostate, ovary, uterus, vagina,
mammary gland, brain, spinal cord, peripheral nerve,
eye, Harderian gland, muscle, bone other organs/tissues with gross lesions.
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(Study No.Ol04,0105) TABLE 10 SURVIVAL ANIMAL NUMBERS AND BODY WEIGHT CHANGES IN MALE RAT
(TWO-YEAR STUDIES)
Ccrltrot 50 ppm 200 ppm 600 ppm
Av.Wt. llo.ot AuJit. %of No.of AvJit. %of No,of Av,J.h, % of No.of Week Slrviv, cent. Strvlv. cmt. Slrvlv, cmt. St.ruiv. m Stu:ly (50) (50) (50> (50>
0 127 (50) 50/50 127 (50) 100 50/50 127 (50) 100 50/50 127 (50) 100 50/50 1 160 (50) 50/50 160 (50) 100 50/50 159 (50) 99 50/50 158 (50) 99 50/50 2 196 (50) 50/50 193 (50) 96 50/50 193 (50) 98 50/50 193 (50) 96 50/50 3 223 (50) 50/50 ZZl (50) 99 50/50 219 (50) 96 50/50 220 (50) 99 50/50 4 247 (50) 50/50 244 (50) 99 50/50 242 (50) 98 50/50 243 (50) 96 50/50 5 266 (50) 50/50 263 (50) 99 50/50 261 (50) 98 50/50 262 (50) 98 50/50 6 282 (50) 50/50 279 (50) 99 50/50 276 (50) 98 50/50 277 (50) 96 50/50 7 299 (50) 50/50 296 (50) 99 50/50 293 (50) 96 50/50 292 (50) 98 50/50 6 314 (50) 50/50 311 (50) 99 50/50 307 (50) 98 50/50 305 (50) 97 50/50 9 326 (50) 50/50 325 (50) 99 50/50 316 (50) 97 50/50 316 (50) 97 50/50
10 336 (50) 50/50 335 (50) 99 50/50 329 (50) 97 50/50 328 (50) 97 50/50 ll 346 (50) 50/50 344 (50) 99 50/50 337 (50) 97 50/50 338 (50) 96 50/50 12 355 (50) 50/50 353 (50) 99 50/50 346 (50) 96 50/50 347 (50) 96 50/50 13 304 (50) 50/50 362 (50) 99 50/50 357 (50) 96 50/50 355 (50) 93 50/50 14 371 (50) 50/50 306 (50) 99 50/50 304 (50) 96 50/50 301 (50) 97 50/50 16 382 (50) 50/50 381 (50) 100 50/50 379 (50) 99 50/50 375 (50) 98 50/50 18 393 (50) 50/50 393 (50) 100 50/50 390 (50) 99 50/50 338 (50) 98 50/50 20 405 (50) 50/50 404 (50) 100 50/50 400 (50) 99 50/50 392 (50) 97 50/50 22 417 (50) 50/50 414 (50) 99 50/50 411 (50) 99 50/50 403 (50) 97 50/50 24 425 (50) 50/50 422 (50) 99 50/50 419 (50) 99 50/50 413 (50) 97 50/50 26 432 (50) 50/50 431 (50) 100 50/50 426 (50) 99 50/50 416 (50) 97 50/50 20 437 (50) 50/50 m (50) 100 50/50 431 (50) 99 50/50 420 (50) 96 50/50 30 447 (50) 50/50 445 (50) 100 50/50 438 (50) 98 50/50 427 (50) 96 50/50 32 455 (50) 50/50 455 (50) 100 50/50 447 (50) 98 50/50 437 (50) 96 50/50 34 460 (50) 50/50 461 (50) 100 50/50 452 (50) 98 50/50 442 (50) 96 50/50 30 465 (50) 50/50 466 (50) 100 50/50 458 (50) 98 50/50 449 (50) 97 50/50 38 471 (50) 50/50 472 (50) 100 50/50 461 (50) 98 50/50 454 (50) 96 50/50 40 475 (50) 50/50 m (5o) 100 50/50 465 (50) 98 50/50 457 (50) 96 50/50 42 480 (50) 50/50 480 (50) 100 50/50 469 (50) 98 50/50 462 (50) 96 S0/50 44 488 (50) 50/50 485 (50) 99 50/50 475 (50) 97 50/50 467 (50) 96 50/50 46 487 (50) 50/50 486 (50) 100 50/50 476 (50) 98 50/50 467 (50) 96 50/50 48 484 (50) 50/50 484 (50) 100 50/50 477 (50) 99 50/50 468 (50) 97 50/50 50 490 (50) 50/50 489 (50) 100 50/50 480 (50) 98 50/50 471 (50) 96 50/50 52 090 (50) 50/50 487 (50) 99 50/50 479 (50) 98 50/50 471 (50) 96 50/50 54 491 (50) 50/50 487 (50) 99 50/50 481 (50) 98 50/50 475 {50) 97 50/50 56 496 (50) 50/50 492 (50) 99 50/50 485 (50) 98 50/50 476 (50) 96 50/50 58 500 (50) 50/50 495 (50) 99 50/50 488 (50) 98 50/50 478 (50) 96 50/50 60 503 (50) 50/50 499 (50) 99 50/50 490 (50) 97 50/50 479 (50) 95 50/50 62 505 (50) 50/50 503 (50) 100 50/50 493 (50) 98 50/50 430 (50) 95 50/50 64 507 (50) 50/50 502 (50) 99 50/50 494 (50) 97 50/50 481 (49) 95 49/50 66 509 (50) 50/50 505 (49) 99 49/50 496 (50) 97 50/50 482 (49) 95 49/50 68 509 (50) 50/50 507 (48) 100 48/50 497 (50) 98 50/50 482 (49) 95 49/50 70 510 (50) 50/50 507 (48) 99 48/50 499 (49) 93 49/50 484 (49) 35 49/50 72 509 (50) 50/50 507 (46) 100 48/50 498 (49) 98 49/50 484 (49) 95 49/50 74 508 (50) 50/50 506 (48) 100 48/50 501 (48) 99 48/50 483 (49) 95 49/50 76 507 (50) 50/50 507 (48) 100 48/50 506 (48) 100 48/50 4e5 (49) 96 49/50 78 499 (50) 50/50 501 (48) 100 48/50 488 (47) 98 47/50 476 (49) 95 49/50 80 495 (50) 50/50 497 (48) 100 48/50 487 (46) 98 46/50 469 (49) 95 49/50 82 491 (50) 50/50 491 (47) 100 47/50 484 (46) 99 46/50 407 (46) 95 46/50 84 494 (48) 48/50 488 (47) 99 47/50 461 (46) 97 46/50 467 (45) 95 '15/50 86 493 (47) 47/50 465 (47) 98 47/50 479 (~5) 97 45/50 461 (45) 94 44/50 68 489 (46) 46/50 483 (47) 99 47/50 479 (45) 93 ~5/50 452 (44) 94 44/50 90 467 (45) 45/50 482 (46) 99 46/50 472 (45) 97 45/50 461 (43) 95 43/50 92 479 (44) 43/50 480 (44) 100 44/50 467 (44) 97 44/50 459 (42) 96 42/50 94 481 (41) 41/50 477 (44) 99 44/50 457 (44) 95 44/50 4t.5 (42) 93 42/50 96 477 (41) 41/50 474 (44) 99 44/50 453 (42) 95 41/50 40 (39) 93 39/50 98 478 (40) 40/50 468 (43) 90 43/50 453 (1o) 95 40/50 433 (37) 92 36/50
100 474 (10) 40/50 461 (42) 97 41/50 445 (38) 94 37/50 43\ (34) 92 33/50 102 467 (40) 40/50 454 (37) 97 37/50 456 (33) 98 33/50 433 (32) 93 32/50 104 459 (38) 37/50 445 (35) 97 3~/50 451 (32) 99 30/50 423 (28) 95 28/50
< >:llo of efiectiua animals,( ):llo of measu-ed animals Av~t:g
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(Study No.Ol04,0105) TABLE 11 SURVIVAL ANIMAL NUMBERS AND BODY WEIGHT CHANGES IN FEMALE RAT
(TWO-YEAR STUDIES)
Cmtrol 50 p;:m 200 """ 600Week en SnxlY
Av.Wt, llo.of Suviv.
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TABLE 14 FOOD CONSUMPTION IN MALE RAT (TWO-YEAR STUDIES)
~
rt"' 0.'< " z?0
0,... -0
0 (J1 -~
Cmtrol 50 PDm 200 PDm 600 PPm
l11eek 01 St1...'dY
Av.FC. llo.ot Av.FC. %of llo.of Av.FC. SLr'VJU. cent. SlrViu.
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TABLE 15 FOOD CONSUMPTION IN FEMALE RAT (TWO-YEAR STUDIES)
~
C/J
"'rt
0.
"'z 0 ~
0"
0 "'"~
0:l!o.of effect1va animals,( J:)lo.of meastrad animals Av.FC.: g
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(Study No.Ol04,0105) TABLE 29 SURVIVAL ANIMAL NUMBERS AND BODY WEIGHT CHANGES IN MALE MOUSE
(TWO-YEAR STUDIES)
C
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(Study No.0!04,0105) TABLE 30 SURVIVAL ANIMAL NUMBERS AND BODY WEIGHT CHANGES IN FEMALE MOUSE
(TWO-YEAR STUDIES)
Central 10 PPm 50 """ 250 """ Au.Wt. No.of Av.wt: %of No.of AuJ~t. %of No.of AvJit, %of No.of
Week SLrViv. cmt. Su-viv. COlt. SLrViu. cont. Su-viv. en StudY
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TABLE 33 FOOD CONSUMPTION IN MALE MOUSE (TWO-YEAR STUDIES)
r:n ~
"' rt
0. '<
z ? 0 ~
0 .... 0 ~
0
"' ~
Cootrol 10 ppm 50 PPm 250 PPm
li'ook Au.FC. No.of
Su-U!U. Au.r:c. %of
co;t. l!o.of
St.ru!U. flv.FG. X of
ctnt. !lo.of
St.ru!U. Au.FC. X of
cent. 1/o.of
Strviv. m StudY (50) (50)
i 2 3
3.8 (SOl 3.8 (50) 3. 9 (50)
50/50 50/50 50/50
3.8 (SO) 3.6 (50) 3. 7 (50)
100 95 95
S0/50 50/50 50/50
3.8 (SO) 3. 7 (50) 3. 7 (50)
100 97 95
50/50 50/50 50/50
3.8 (50) 3.8 (50) 3.8 (50)
100 100 97
S0/50 50/50 50/50
4 4. 0 (50) 50/50 3.9 (50) 90 50/50 3. 9 (50) 98 50/50 3.9 (50) 98 50/50 5 4.0 (501 50/50 3.9 (50) 98 50/50 1.0 (50) 100 50/50 3. 9 (50) 98 50/50 6 7
1.1 (50) 4.1 (50)
50/50 50/50
3. 9 (50) 3.8 (50)
95 93
50/50 50/50
3.9 (50)' 1.0 (50)
95 98
50/50 50/50
3. 9 (50) 3.9 (50)
95 95
50/50 50/50
8 1.1 (50) 50/50 1.0 (50) 98 50/50 1.1 (50) 100 50/50 1.0 (50) 98 50/50 9 1.2 (50) 50/50 1.1 (50) 98 50/50 1.i (50) 98 50/50 1.1 (50) 98 50/50
10 1.1 (50) 50/50 1.1 (50) 100 50/50 1.1 (50) 100 50/50 1.0 (50) 98 50/50 11 1.2 (50) 50/50 1.1 (50) 98 50/50 1.1 (50) 98 50/50 u (50) 98 50/50 12 13
4.3 (50) 1.2 (50)
50/50 50/50
1.1 (50) 1.! (50)
95 98
50/50 50/50
1.2 (50) 1.1 (50)
98 98
50/50 50/50
1.2 (50) 1.0 (501
98 95
50/50 50/50
11 4.2 (50) 50/50 u (50) 100 50/50 1.2 (50) 100 50/50 1.2 (50) 100 50/50 18 4.1 (50) 50/50 1.2 (50) 95 50/50 u (50) 100 50/50 1.3 (50) 98 50/50 22 26
4.1 (50) 4.6 (50)
50/50 50/50
4.1 (50) 1.5 (50)
100 98
50/50 50/50.
u (50) 4.6 (50)
100 100
50/50 50/50
1.1 (50) 4.1 (50)
93 96
50/50 50/50
30 31
1.6 {19) 4.6 (49)
49/50 49/50
4.5 {50) 4.5 (50)
98 98
50/50 50/50
1.6 (50) 4.6 {50)
100 100
50/50 50/50
1.1 {50) 1.5 (19)
96 98
50/50 19/50
38 1.8 (49) 19/50 1.6 (50) 96 50/50 1. 7 (50) 98 50/50 4.7 (19) 98 19/50 12 1. 7 (48) 18/50 1.6 {19) 98 49/50 4.6 (19) 98 19/50 1.5 (19) 96 19/50 46 1.6 (48) 18/50 1. 7 (49) 102 19/50 1.6 (19) 100 19/50 1.5 (49) 98 49/50 50 4. 7 (16) 46/50 1.6 {19) 98 19/50 1. 7 (19) 100 19/50 1.6 (49) 98 49/50 52 1. 7 (16) 16/50 1.6 (19) 98 49/50 1.8 (18) 102 18/50 1.5 (19) 96 19/50 51 1.7 (16) 16/50 1.5 {19) 96 19/50 1.8 (18) 102 18/50 1.6 (19) 98 19/50 58 5.0 {16) 16/50 4.8 (18) 96 18/50 5.1 (18) 102 18/50 1.8 {19) 96 19/50 62 1.7 (16) 16/50 1. 7 (18) 100 18/50 1.9 {48) 101 18/50 1.6 {19) 98 19/50 66 4.8 {16) 46/50 1.7 (17) 98 17/50 4.9 (171 102 17/50 4. 7 (19) 98 18/50 70 4.8 {46) 46/50 1. 7 (171 98 17/50 1.8 {16) 100 16/50 1.7 {481 98 17/50 74 78
1.8 {16) 5.1 {41)
16/50 14/50
1.9 (171 5.0 Wl
102 98
17/50 47/50
1.7 (16) 5.1 {13)
98 100
41/50 13/50
4.4 (17) 5.0 {16)
92 98
17/50 16/50
82 5.2 {41) 41/50 5.0 {171 96 17/50 5.2 (121 100 11/50 1.9 {11) 91 11/50 86 5.2 {121 12/50 5.0 {16) 96 16/50 5.1 (11) 98 11/50 1.6 (111 88 10/50 90 5.2 (42) 12/50 5.0 {16) 96 16/50 5.1 (39) 98 38/50 1.8 (39) 92 39/50 91 5. 0 (11) 11/50 1.9 (11) 98 41/50 1.9 (36) 98 31/50 1.6 {36) 92 35/50 98 5.0 (36) 36/50 5.0 (41) 100 10/50 5.1 (31) 102 31/50 1.6 (33) 92 31/50
102 4.9 (36) 31/50 1.8 (37) 98 37/50 1.9 (30) 100 30/50 1.1 (251 90 25/50 101 5.1 (32) 31/50 1.0 (35) 91 35/50 1. 7 (28) 92 28/50 1.5 (21) 88 22/50
< ):t/o.of affective ammals,( ):Jio.of measu-ed an1mals Av.FC.:g
-
TABLE 34 FOOD CONSUMPTION IN FEMALE MOUSE (TWO-YEAR STUDIES)
"' ~
-
APPENDIX L 1
HISTOLOGICAL FINDINGS NON-NEOPLASTIC LESIONS
(TWO-YEAR STUDIES:SUMMARY)
RAT:MALE:DEAD AND MORIBUND ANIMALS
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STUDY NO. : 0104 HISTOLOGICAL FINDHIGS ' NON-NEOPLASTIC LESIONS (SUIHIARY) ANI HAL : RAT F344 DEAD AND MORIBUND ANI!IAI.S (0-105Wl REPORT TYPE : A1 SEX : HALE PAGE :
Group Name No. of Animals
Control 13
50 ppm 16
200 20 ""' 600
ppm 22
(1) (3) (4)
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('_,.
STUDY NO. ' 0104 ANIMAL ' RAT F344 REPORT TYPE ; AI SEX ' HALE
II!STOLOGICAL FINDINGS ' NON-NEOPLASTIC LESIONS DEAD AND HORIDUND ANIMALS (0-1051/J
(SUHHARYJ
PAGE ; 2
Organ_ Findings
GrOUP Name No. of Animals
(%)
Control 13
(3) (%) (%)
(%)
(%)
50 "'"16 (%) (%)
(4)
(%) (%)
200 PP> 20
(%) (%)
(%)
(j)
(%)
600 PPm 22
(3) (%) (%)
(4)
(%)
[llemataxuetic SYstem I
l:rne marrau grarulatioo
myelofii:JrosJs
reticulosis
SPLeen hemorrhage
dePOSit of hemosiderin
fii:JrosJS
extramedullarY hematopoJesis
0 0)
0 OJ
0 01
0 0)
j
8)
0 0)
2 ( 15)
0 ( 0)
0 ( OJ
0 ( 01
0 ( 0)
2 ( I5)
0 ( 01
0 ( 01
(
(
(
(
(
(
(
0 0)
0 OJ
0 0)
0 0)
0 0)
0 01
l 8)
(
(
(
(
(
(
(
0 0)
0 Ol
0 OJ
0 0)
0 01
0 0)
0 OJ
l 0 ( 6) ( OJ
0 0 ( 0) ( 0)
0 0 ( 0) ( OJ
0 0 ( 0) ( 0)
j 0 ( 6J ( 0)
0 0 ( 01 ( 01
3 2 ( 19) ( 131
(
(
(
(
(
(
(
0 OJ
0 OJ
0 0)
0 0)
0 0)
0 0)
l 61
(
(
(
(
(
(
(
0 0)
0 0)
l 6)
0 0)
0 0)
0 01
0 Ol
0 ( 0) (
l ( 5) (
0 ( 0) (
0 ( 0) (
0 ( 0) (
l ( 51 (
6 ( 30) (
0 OJ
0 OJ
0 0)
l 5)
0 0)
0 01
0 Ol
(
(
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
0 0)
0 01
0 OJ
(
(
(
(
(
(
(
0 01
0 OJ
0 0)
0 0)
0 01
0 01
0 Ol
(
(
(
(
(
(
(
l 5)
0 OJ
l 5)
0 OJ
2 9)
l 51
j
51
(
(
(
(
(
(
(
0 OJ
0 OJ
0 Ol
0 0)
l 5)
2 91
2 9)
(
(
(
(
(
(
(
0 OJ
0 01
0 OJ
0 0)
0 01
0 01
2 91
(
(
(
(
(
(
(
0 OJ
0 01
0 OJ
0 OJ
0 0)
0 Ol
0 01
(Cirrulato-Y sYSteml
heart diLatation
thrmbus
mmera l izati 01
myocardial fii:r'osJs
0 OJ
0 OJ
l Bl
4 ( 3ll
(
(
(
(
0 01
0 0)
0 0)
l Bl
(
(
(
(
0 0)
0 OJ
0 Ol
0 Ol
(
(
(
(
0 01
0 0)
0 01
0 0)
0 ( 01
0 ( 0)
l ( 6J
3 ( !91
(
(
(
(
0 0)
0 0)
0 Ol
0 Ol
(
(
(
(
0 01
0 0)
0 Ol
0 0)
(
(
(
(
0 01
0 0)
0 OJ
0 Ol
l ( 5)
0 ( OJ
0 ( OJ
8 ( 401
(
(
(
(
0 01
0 0)
0 0)
0 0)
(
(
(
(
0 0)
0 OJ
0 0)
0 0)
(
(
(
(
0 01
0 0)
0 0)
0 0)
0 ( OJ
2 ( 9)
0 ( Ol
8 ( 36)
(
(
(
(
0 OJ
0 OJ
0 Ol
0 Ol
(
(
(
(
0 OJ
0 0)
0 Ol
0 Ol
(
(
(
(
0 0)
0 0)
0 Ol
0 0)
Significant difference ;
(IIPTI50)
*;P~0.05 "'* : p ;,;:;; 0.01 Test of ChJ Square (l):Slisht : Moderate :Uarked :Severe
BAIS2
-
STUDY ND. : 0104 HISTOLOGICAL FINDINGS : NON-NEOPLASTIC LESIONS (SUIIIIARYJ
ANI HAL RAT F344 DEAD AND IIOR!BUND ANIMALS (0-IOSWJ
REPORT TYPE SEX
AI HALE PAGE
3
GrOlP llama Control 50 ppm 200 ppm 600 ppm
Organ__ Findings
No. of Ammals (I)
(%)
13 (%)
(%)
(4)
(%) (I)
(%)
16 (%)
(3) (%)
{%)
(I)
(%)
20 (2) {%)
(3) (%)
(4)
(%) (I)
(%)
22 (%)
(3) (%)
(4)
(%)
[CirrulatcrY systemj
arteryIacrt m\neralization:artery I 81 (
0 0) (
0 OJ (
0 OJ (
0 OJ (
0 0) (
0 OJ (
0 OJ (
0 OJ (
0 0) (
0 0) (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ
(Dieestive sYStem]
tooth lnflamnatlon 0 0 OJ ( OJ (
0 0) (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ
l 0 ( SJ ( 0) (
0 OJ (
0 OJ
1
( 51 0
( OJ ( 0 0) (
0 OJ
stooach congest ien I 0 8J ( OJ (
0 OJ (
0 0) (
0 OJ (
0 OJ (
0 OJ (
0 OJ
0 0 ( OJ ( OJ (
0 0) (
0 OJ
0 ( OJ
0 ( OJ (
0 OJ (
0 OJ
mmara Uzat h::n 0 0 OJ ( O) (
l 8) (
0 0) (
1 6) (
l 6) (
0 OJ (
0 OJ
0 0 ( OJ ( OJ (
0 0) (
0 OJ
0 ( OJ
0 ( OJ (
0 OJ (
0 OJ
ulcer:forestomach 2 2 ( 15) ( 15) (
0 OJ (
l 8) (
l 6) (
1 6) (
0 OJ (
0 OJ
2 3 ( 10) ( IS) (
0 OJ (
0 OJ
3 ( 14)
-
"' (SUIIHARYl STUDY NO. : IIDN-NEOPLAST1C LESIONS ' 0104 111STOLOG1CAL F111D1NGS
ANIMAL : RAT F344 DEAD AND MORIBUND ANIMALS (0-1051;)
REPORT TYPE : A1 PAGE ; 4
SEX : HALE
ppm 600 ppm Group Name Control 50 ppm 200 22 flo. of Ammals 13 16 20
(4) (3)
-
STUDY NO. ' 0104 IIISTOLOGICAL FI!IDINCS ' NON-NEOPLASTIC LESIONS (SUNIIARY)
ANI HAL : RAT F344 DEAD AND HOR!BUND ANIMALS (0-!0511)
REPORT TYPE SEX
: A! : HALE PACE ; 5
Dr9ill1__ Findinss
Group Name No. of Animals
(])
(%)
Ccrrtrol 13
(3) (%) (%)
-
" STUDY NO. AIIIHAL REPORT TYPE SEX
' DID4 : RAT F344 : AI : HALE
IIISTDLOGICAL FINDINGS ; NON-NEOPLASTIC LES!DNS DEAD AND HDRIBUIID AN!HALS (0-lOSWI
(SUIIIIARY)
PAGE ; 6
Organ Findings
Cirot.p Name No. of Animals
(%)
Control 13
-
SfUDY ND. : 0104 I!ISTDLOGICAL FINDINGS : NON-I!EDPLASTIC LESIONS (SUHHARY)
ANI HAL : RAT F344 DEAD AIID MORIBUND ANIMALS (0-!05W)
REPORT TYPE : AI SEX : HALE
PAGE : 7
Group Name No. of Animals
Control 13
50 16 - 200 ppm 20 600 "".22
Organ___ Findings (!)
(%) (%) (%)
(%)
(!)
(%) (%) (%)
(%)
(!)
(%) (%) (%)
(%)
(!)
(%) (%) (%)
(%)
[Neru::us sYstem}
l:::raln mineralization 0 0) (
0 0) (
0 0) (
0 0)
1 ( 6) (
0 0)
0 ( 0) (
0 0)
0 ( 0)
0 ( 0)
0 ( OJ (
0 OJ
0 ( 0) (
0 0) (
0 0) (
0 0)
hYaline body 3 ( 23) (
0 0) (
0 0) (
0 0)
5 ( 31) (
0 0)
0 ( 0) (
0 0)
2 ( !OJ
0 ( OJ
0 ( OJ (
0 0)
5 ( 23) (
0 0) (
0 0) (
0 OJ
ossea.JS metaplasia 0 0) (
0 OJ (
0 OJ (
0 0)
2 ( 13J (
0 0)
0 ( OJ (
0 0)
0 ( 01
0 ( 0)
0 ( 0) (
0 0)
0 ( 01 (
0 0) (
0 0) (
0 0)
SPinal ccrd slios1s 0 0) (
1 8) (
0 0) (
0 OJ
0 ( OJ (
0 0)
0 ( 0) (
0 0)
0 ( 01
0 ( 0)
0 ( 0) (
0 0)
0 ( 0) (
0 OJ (
0 0) (
0 0)
[Special sense orsans/appandasel
eye cataract 0 0) (
0 OJ (
0 0) (
0 0)
1 ( 6) (
0 0)
0 ( 0) (
0 0)
0 ( 0)
2 ( 10)
0 ( 0) (
0 0)
0 ( 0) (
0 01 (
0 0) {
0 0)
retinal atrOPhY 1 8) (
0 0) {
0 0) (
0 0)
1 ( 6J (
0 0)
2 ( 13) (
0 0)
0 ( 01
0 ( 0)
2 ( !0) (
0 0)
0 ( 0) (
0 0) (
0 0) (
0 OJ
keratitis 0 0) (
0 0) (
0 0) (
0 0)
0 ( 0) (
1 6)
0 ( 0) (
0 0)
0 ( 0)
0 ( 0)
0 ( 0) (
0 OJ
0 ( 0) (
0 OJ (
0 0) (
0 0)
hemorrhase:retina 0 OJ (
0 0) (
0 0) (
0 0)
0 ( 0) (
0 OJ
0 ( 0) (
0 OJ
0 ( 0)
0 ( OJ
0 ( 0) (
0 OJ
1 ( 5J (
0 OJ (
1 5J (
0 0)
!larder sl degeneration 0 OJ (
0 0) (
0 OJ (
0 0)
0 ( OJ (
0 OJ
0 ( OJ (
0 0)
1 ( 5)
0 ( 0)
0 ( 0) (
0 OJ
0 { OJ (
0 0) (
0 OJ (
0 0)
1nflarrmatim 0 OJ (
0 OJ (
0 OJ (
0 OJ
0 ( 0) (
1 6)
0 ( 0) (
0 0)
0 ( OJ
0 ( OJ
0 ( OJ (
0 0)
0 ( 0) (
0 OJ (
0 OJ (
0 OJ
(Husculosketetal systemJ
rruscle necrOSIS 0 01 (
0 0) (
0 0) (
0 OJ
0 ( 0) (
1 6)
0 ( OJ (
0 0)
0 ( 0)
0 ( Ol
0 ( OJ (
0 OJ
4 ( 18) (
0 OJ (
0 0) (
0 0)
Si91iflcant difference ; *!P;:;i0.05 ** ; p ;;:; 0.01 Test of Chi Square
-
,:,. S11IDY NO. ' 0104 ANI HAL ' RAT F344 REPORT TYPE : AI SEX ; HALE
IIISTOLOGICAL FINDINGS ; 11011-NEOPLASTIC LESIONS DEAD AND MORIBUND AN!HALS (0-105N)
(SUMIIARY)
PAGE ' 8
()rgafL._ Findings
Gro..p Name No. of Animals
(!) (%)
Control 13
(3) (%) (%)
(%)
(!) (%)
50 PPm 16
(%) (%)
(%)
(!) (%)
200 ppm 20
(%) (%)
(%)
-
APPENDIX L 2
HISTOLOGICAL FINDINGS :NON-NEOPLASTIC LESIONS
(TWO-YEAR STUDIES:SUMMARYl
RAT:FEMALE:DEAD AND MORIBUND ANIMALS
-
STUDY NO. ' 0104 IIISTOLOGICAL FINDINGS : NON-NEOPLASTIC LESIONS (SUIIHARY)ANI HAL : RAT F344 DEAO AIID NORIBUND ANIHALS (0-!0SW) REPORT TIPE : AI SEX : FEMALE PAGE ; 9
Gn:JI..l) Name Central No. of Ammals 8
(!) (3)
-
STUDY ND. ' 0104 IIISTOLOG!CAL FINDINGS ; NON-NEOPLASTIC LESIONS (SUIHIARYIAll! HAL ' RAT F344 DEAD AND IIORIBUNO ANIIIALS (0-10511) REPORT TYPE SEX
: A 1 : FEHALE PAGE ; 10
GrOUP Name Control 50 PPm 200 ppm 600 ppm
No. of Animals 8 16 16 16
Organ__ Findings
-
STUDY liD. : DID4 lllSTOLOGICAL FlliDINCS : NON-NEOPLASTIC LESIONS (SUIIHARY)
ANI HAL : RAT F344 DEAD A!ID MORIBUND ANIMALS (0-IOSW) REPORT TYPE SEX
: AI : FEHALE PAGE : 11
Group Name Control No. of Animals 8
50 ppm I6
zoo ppm I6
600 ppm I6
Organ Findings (!) (%) (%)
(4) (%) (%)
(3) (%) (%) C%1
(4)
(%) (!)
(%) (%)
(%) (%)
(!)
(%) (%)
(%)
(4)
(%)
[CirculatrrY sYStem!
heart mYOCardial fibros1s 1 0 ( I3) ( 0) (
0 0 OJ ( Ol
2 0 0 ( I31 ( 01 ( 01 (
0 OJ
1 ( 6J
0 ( OJ
0 0 ( OJ ( OJ
3 ( I91
0 ( Ol (
0 0) (
0 01
[Disestiue SYStemJ
stonach ulcer:forestomach j 2 ( I31 ( ZSJ (
0 0 OJ ( Ol
0 3 0 ( 01 ( I91 ( 01 (
0 01
2 ( I31
3 ( 191
0 0 ( 01 ( Ol
1 ( 61
2 ( 131 (
1 61 (
0 01
hYPerplasia:forestomach 2 0 ( 251 ( 0) (
0 0 01 ( 01
I 0 0 ( 61 ( 01 ( 01 (
0 01
0 ( OJ
j
( 6) 0 0
( OJ ( 01 4
( 251 2
( I3) ( 0 01 (
0 01
erosion:glandular stomach j 0 ( I31 ( 0) (
0 0 0) ( 0)
3 0 0 ( I91 ( 01 ( 01 (
0 01
1 ( 6)
0 ( 01
0 0 ( 0) ( 01
2 ( 131
0 ( OJ (
0 0) (
0 0)
ulcer:glandular stomach 1 0 ( I3J ( 0) (
0 0 OJ ( OJ
3 0 0 ( 19) ( 0) ( OJ (
0 OJ
l ( 6)
0 ( 0)
0 0 ( Ol ( OJ
6 ( 38J
0 ( OJ (
0 OJ (
0 OJ
small mtes ulcer 0 0 OJ ( OJ (
0 0 OJ ( OJ
l 0 0 ( 61 ( OJ ( 0) (
0 OJ
0 ( OJ
0 ( 01
0 0 ( OJ ( OJ
0 ( Ol
0 ( OJ (
0 OJ (
0 OJ
Large tntes ulcer 0 0 OJ ( OJ {
0 0 OJ ( OJ
0 0 0 ( OJ ( OJ { OJ (
0 OJ
0 ( OJ
0 ( OJ
0 0 ( 0) ( OJ
0 ( OJ
l ( 6J (
0 OJ (
0 OJ
liver necrosis:central 0 0 OJ ( OJ (
0 0 0) ( 01
0 0 0 ( OJ ( Ol ( 0) (
0 OJ
z ( I3)
0 ( 0)
0 0 ( OJ ( 01
l ( 6J
l ( 6J (
0 0) (
0 OJ
fattY change 1 1 ( 13) ( I3) (
0 0 0) { Ol
0 0 0 ( 0) ( 0) ( 01 (
0 OJ
0 ( Ol
0 ( 0)
0 0 ( 01 ( 01
1 ( 6)
l ( 6) (
0 0) (
0 0)
desenerati on:central 0 0 ( 01 ( 0) (
0 0 0) ( 0)
0 1 0 ( 0) ( 6J ( 0) (
0 0)
0 ( 0)
0 ( 0)
0 0 ( OJ ( OJ
0 ( 0)
0 ( OJ (
0 OJ (
0 0)
sranulatioo 3 0 ( 38) ( OJ (
0 0 OJ ( OJ
l 0 0 ( 61 ( 0) ( OJ (
0 01
0 ( 0)
0 ( 01
0 0 ' ( 01 ( 0)
0 ( Ol
0 ( OJ (
0 01 (
0 ' 01
Significant difference t * : p ;;;,;; 0.05 n: ; p ;:;i 0.01 Test of Chi Square :Slisht :Moderata :Marked :Severe
(liPTISOI DAISZ
/~
-
STUDY NO. ' 0104 HISTOLOGICAL FINDINGS ; NON-NEOPLASTIC LESIONS (SUIIIIARYJ
ANIMAL ' RAT F344 DEAD AIIO IIOR!BUNO AJI!HALS (0-105W) REPORT TYPE SEX
: AI ' FEMALE
PAGE 12
Organ....___ Findings
Group Name No. of Amrnals
(%)
Ca
(2) (%)
ntrol 8
(3) (%)
(4)
(%) (%)
50 16 """
(2)
(%) (3) (%)
(4)
(%) (!)
(%)
200 16
(%)
ppm
(%)
(4)
(%) (!)
(%)
600 16
(2) (%)
ppm
(%)
(4)
(%)
[Digestive sYStemj
liver baSOPhi lie ceLL focus J ( 13) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0)
0 ( 0) (
0 OJ (
0 0) (
0 OJ (
0 0) (
0 OJ (
0 OJ (
0 0)
mixed cell focus 0 ( 0) (
0 OJ (
0 OJ (
0 0) (
0 0) (
0 0) (
0 OJ (
0 OJ
3 ( 19) (
0 OJ (
0 0) (
0 0) (
J 6) (
0 0) (
0 0) (
0 OJ
bile duct hYPerplasia 3 ( 38) (
0 0) (
0 0) (
0 0) (
J 6) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 % OJ (
J 6) (
0 0) (
0 0) (
0 0)
cholangJofibrosis 0 0) (
0 0) (
0 0) (
0 0) (
0 OJ (
J 6) (
0 OJ (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 OJ (
0 OJ (
0 0) (
0 OJ
pancreas atrOPhY 0 0) (
0 0)
0 ( 0)
0 ( 0)
l ( 6J
0 ( OJ (
0 OJ (
0 OJ
0 ( 0)
0 ( 0) (
0 0) (
0 0)
0 ( OJ
0 ( 0)
0 ( 0) (
0 0)
[Un nary systemJ
kichaY herocrrhase 0 OJ (
0 0)
0 ( OJ
0 ( OJ
0 ( 0)
0 ( 0) (
0 0) (
0 0)
0 ( 0)
0 ( 0) (
J 6) (
0 0)
0 ( 0)
0 ( 0)
0 ( 0) (
0 0)
ciTm!c neplrepathy 4 ( 50) (
0 0)
J ( 13)
J ( 13)
10 ( 63)
2 ( 13J (
J 6) (
0 OJ
6 ( 38)
2 ( 131 (
J 6J (
0 OJ
5 ( 31)
3 ( !9J
2 ( 13) (
J 6)
stomerulosclerosls 0 0) (
0 0) (
0 0) (
0 0)
0 ( OJ (
0 0) (
0 0) (
0 OJ
J ( 6J (
0 OJ (
0 OJ (
0 OJ
0 ( 0) (
0 0) (
0 0) (
0 0)
ruclear enlarsement:prnxw~al tl..bule 0 OJ (
0 0) (
0 0) (
0 OJ
0 ( 0) (
0 0) (
0 OJ (
0 0)
0 ( 0) (
0 0) (
0 0) (
0 0)
4 ( 25) (
0 0) (
0 0) (
0 0)
[l?n:bcrme systemj
Pituitary cYSt l ( 13) (
0 0) (
0 OJ (
0 0)
4 ( 25) (
0 OJ (
0 0) (
0 OJ
3 ( 19) (
0 0) (
0 0) (
0 0)
0 ( 0) (
0 0) (
0 0) (
0 0)
Significant difference : l: : p ;:a 0.05 u ; p ;;a 0.01 Test of 011 Square :Slisht :Moderate :Marked :Seuere
(IIPT150) BAIS2
"
-
---------------
STUDY ND. : 0104 IIISTOLOGICAL FINDINGS : NON-NEOPLASTIC LESIONS (SUIIIIARYl
ANI HAL : RAT F344 DEAD AND MORIBUND ANIMALS (0-10511)
REPORT TYPE : AI SEX : FEHALE PAGE
: 13
GrOUP Name Control 50 ppm 200 ppm 600 ppm
Orga"- Findings
No. of Animals 8 (3) (%) (%) (%) (%)
(%)
16 (2) (%) (%)
(4)
(%) (%)
16 (3) (%) (%)
(%)
(%)
16 (2) (3)
(%) (%) (%)
{frlcbcnne sYStemj
pituitary hYperpLas 1a j 0 0 0 ( 13) ( 0) ( 0) ( 0)
4 ( 25) (
0 0 0) ( 0) (
0 0)
4 ( 25)
0 0 ( Ol ( 0) (
0 OJ
4 ( 25)
0 0 ( 0) ( 0)
0 ( 0)
thyroJd G-cell hyperplasia 0 0 0 0 0) ( 0) ( 0) ( 0)
0 ( OJ (
0 0 OJ ( Ol (
0 0)
0 ( 0)
0 0 ( 0) ( 0) (
0 0)
j
( 6) 0 0
( OJ ( OJ 0
( 0)
ad-enal Pelios1s-like lesion 0 0 0 0 0) ( Ol ( OJ ( Ol
0 ( Ol (
0 0 OJ ( Ol (
0 Ol
j
( 6J 0 0
( 0) ( OJ ( 0 0)
0 ( OJ
0 0 ( 0) ( OJ
0 ( Ol
necrosis 0 0 0 0 0) ( 0) ( 0) ( 0)
I ( 6) (
0 0 0) ( 0) (
0 OJ
0 ( 0)
0 0 ( OJ ( OJ (
0 OJ
0 ( OJ
2 0 ( 13J ( 0)
0 ( OJ
hyperplasJa:cortical cell 0 0 0 0 0) ( OJ ( OJ ( OJ
4 ( 25J (
0 0 OJ ( 0) (
0 OJ
2 ( !3J
0 0 ( 0) ( OJ I
0 0)
0 ( OJ
0 0 ( OJ ( OJ
0 ( OJ
hYPerplasJa:medulla 0 0 0 0 OJ ( 0) ( OJ ( 0)
0 ( 0) (
0 0 OJ ( 0) (
0 OJ
0 ( OJ
0 0 ( 0) ( 0) (
0 OJ
2 ( 13)
0 0 ( OJ ( 0)
0 ( OJ
focal fatty char19e:cortex 0 0 0 0 0) ( 0) ( 0) ( 0)
0 ( OJ (
0 0 OJ ( 0) (
0 OJ
2 ( 13J
j 0 ( 6) ( OJ (
0 0)
0 ( OJ
0 0 ( 0) ( 0)
0 ( OJ
[Reproci.x::tiue s>'Steml
uterus cYStic endanetnal hyperplasia l 0 0 0 ( 13) ( 0) ( 0) ( 0)
3 ( 19) (
0 0 OJ ( Ol (
0 0)
0 ( 0)
2 0 ( 13) ( 0) (
0 0)
2 ( !3)
l 0 ( 6J ( 0)
0 ( 0)
marrrnary gl duct ectasta 0 0 0 0 0) ( 0) ( 0) ( 0)
0 ( Ol (
0 0 0) ( 0) (
0 OJ
0 ( O)
0 0 ( OJ ( 0) (
0 0)
l ( 6)
0 0 ( 0) ( 0)
0 ( 0)
hYperplasia l 0 0 0 ( !3J ( OJ ( OJ ( 0)
0 ( OJ (
0 0 0) ( OJ (
0 0)
l ( 6)
0 0 ( OJ ( OJ (
0 OJ
0 ( OJ
0 0 ( OJ ( OJ
0 ( 0)
[Nen.rus SYStem!
!:ram hemorrhage 0 0 0 0 OJ ( Ol ( OJ ( OJ
2 ( 13J (
0 0 0) ( Ol (
0 OJ
0 ( 0)
0 0 ( OJ ( 0) (
0 0)
l ( 6)
0 0 ( 0) ( 0)
0 ( OJ
Si91ificant difference ; * ; p ~ 0.05 ** ; p ;;:;;; 0.01 Test of Chi Scruare
-
STUDY NO. ' 0104 HISTOLOGICAL FlllDINGS : NON-NEOPLASTIC LESIONS (SUIIIIARYJ(0-IOSW) ANI HAL IIORIBUND ANIMALS ' RAT F344 DEAD AND
REPORT TYPE : AI PAGE 14 SEX : FEMALE
ppm 200 ppm 600 ppm GraUl Name Control 50 16 16 No. of Ammats 8 16
(!) (4) (%) (%) (%) (%) (%) {l-gan__ (%) (%) (%) (%) (%) (%) (%) Findings (%) (%) (%) (%)
[Nen.oos SYStem)
0 0 0 0 I 0 0 0 0 0 0 0 !ram necros i s: fuca L 0 0 0 0 ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) 0) ( 0) ( 0) ( 0) ( 6) { 0) ( 0) ( 0) ( OJ ( 0)
I 0 0 0 0 0 0 0 0 0 0 0 mineralization 0 0 0 0 ( 0) ( 0) ( 6) ( 0) ( 0) ( OJ 0) ( OJ ( 0) ( OJ ( 0) ( 0) ( OJ ( OJ ( OJ ( 0)
4 0 0 0 2 0 0 0 2 0 0 0 hYaline bodY 2 0 0 0 ( 13) ( 0) ( 0) ( 0) ( 25) ( 0) ( Ol ( OJ ( 25J ( 0) ( 0) ( 0) ( 13) ( OJ ( 0) ( 0)
I 0 0 0 0 0 0 0 0 0 0 0 0 0 SPinal a:rd herrcrrhasa 0 0 0) ( 0) ( 6) ( 0) ( 0) ( 0) 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) (
0 2 0 0 0 0 0 0 0 0 0 0 0 necrosis 0 0 0 ( OJ ( OJ ( OJ ( 13) ( OJ ( 0) 0) ( 0) ( 0) ( OJ ( 0) ( 0) ( OJ ( 0) ( 0) ( 0)
[SDec!al sense orsans/appandagej
0 0 0 0 0 I 0 0 0 2 0 eye I cataract 0 0 0 0 ( 0) ( 0) ( 13) ( OJ ( OJ ( 0) 0) ( 0) ( 0) ( 0) ( 6J ( OJ ( 0) ( OJ ( 6J ( 0)
0 0 2 0 0 1 0 0 0 0 1 0 retinal atrophy 0 0 0 0 ( 6) ( 0) ( OJ ( 0) ( !3J ( Ol 0) ( 0) ( 0) ( 0) ( 0) ( 6) ( 0) ( 0) ( 0) ( 0)
0 0 0 0 0 0 I 0 0 0 I degeneration:cornea I 0 0 0 0 ( 6) ( OJ ( 0) ( 0) ( 6) ( 0) ( 0) ( OJ ( 13) ( OJ ( 0) ( OJ ( 0) ( 0) ( 0) ( 0)
0 I 0 0 0 0 0 0 0 0 1 0 0 hemorrhasa:retina 0 0 0 ( 6) ( 0) ( 0) ( 0) ( 6) ( OJ ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0)
0 0 0 0 0 0 0 0 0 0 0 0 0 Harder gl inflamnaticn I 0 0 ( 0) ( 0) ( 0) ( 0) ( 0) ( OJ ( 0) ( OJ ( 13) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( OJ
[Musculoskeletal SYstem!
0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 bene osteosclerosis 0 ( OJ ( OJ ( 0) ( 0) ( 0) ( 0) ( 0) ( OJ OJ ( 0) ( OJ ( 0) ( 13) ( 0) ( 0) ( 0)
:Sli9ht :floderate :Marked :Severe Si!:nificant difference ; '* : p ;:;;:;: 0.05 n ; P ;:;i 0.01 Test of Cht Sc;uare ~ - - - - ~~-----
6
-
:; STUDY NO. ' OI04 AIIIHAL ' RAT F344 REPORT TYPE ; AI SEX ; FEHALE
HISTOLOGICAL FINDINGS liON-NEOPLASTIC LESIONS DEAD AND IIORIDUIID ANlliALS (0-IOSWJ
(SUIIIIARYJ
PAGE ; IS
Organ. Findings.
Group Name No. of Ammals
-
APPENDIX L 3
HISTOLOGICAL FINDINGS :NON-NEOPLASTIC LESIONS
(TWO-YEAR STUDIES:SUMMARYJ
RAT:MALE:SACRIFICED ANIMALS
-
STUDY NO. ' 0104 II!S!OLOG!CAL FINDINGS : NON-NEOPLASTIC LESIONS (SUMMARY)
Alii MAL : RAT F344 SACRIFICED ANI!IALS (!OSW) REPORT TYPE : AI
PAGE : SEX : HALE
ppm 600 ppm Gro.;p Name Control 50 PPm 200 28 No. of Animals 37 34 30
(3) (%) (%) (%) (%) (%) (%) (%) Organ_ (%) (%) Findings (%) (%) (%) (%) (%) (%) (%)
[ I nt69..100f1tarY sYStem/appandagel
0 0 0 0 0 0 0 0 0 skln/app abscess 0 0 0 0 1 0 0 ( 0) ( OJ ( OJ 0) ( OJ ( 0) ( OJ ( 3) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( OJ ( OJ
0 0 0 1 0 0 0 epidermal cYSt 0 0 0 0 1 0 0 0 3 ( 4J ( OJ ( O) ( OJ 0) ( OJ ( OJ ( 0) ( 3) ( 0) ( OJ ( 0) ( 10) ( OJ ( 0) ( OJ
[RSSDtratr:rY SYstem!
0 0 0 0 1 0 0 0 nasal cauit 0 ttronbus 0 0 0 0 0 0 0 ( 0) ( 0) ( 4) ( 0) ( OJ ( 0) 0) ( 0) ( OJ ( 0) ( 0) ( OJ ( OJ ( 0) ( 0) ( OJ
1 0 0 2 2 0 0 eos100Philic chanse:otfactory epithelium 3 3 0 0 4 2 4 0 2 ( 7J ( 7) ( 0) ( 0) 8J ( 8J ( 0) ( 0) ( 12) ( 6) ( 12J ( OJ ( 7) ( 3) ( 0) ( OJ
6 4 0 0 4 0 0 0 eostnDPhilic chanse:reSPtratory epithelium 11 1 0 0 12 4 0 0 ( 14J ( OJ ( 0) ( 0) ( 30J ( 3) ( OJ ( OJ ( 35J ( 12J ( OJ ( OJ ( 20J ( 13J ( 0) ( 0)
0 0 0 0 0 0 0 resptratorY metaPtasta 0 0 0 0 1 0 0 0 0 ( OJ ( 0) ( 0) ( OJ ( 0) ( OJ ( 0) ( OJ ( 3) ( OJ ( OJ ( OJ ( 0) ( 0) ( OJ ( 01
1 4 5 4 1 5 5 2 0 1nf lamnat ien: fcre 19!1 bodY 10 3 1 1 1 8 1 ( !8J ( 18) ( 7J ( OJ ( 27) ( 8J ( 3J ( 3) ( 3J ( 24J ( 3J ( 3) ( 13J ( 17) ( 13J ( 3J
0 0 0 0 0 0 0 0 0 0 0 0 llf19 hemorrhage 0 1 0 0 ( OJ ( OJ ( OJ OJ ( 3J ( OJ ( 0) ( OJ ( 0) ( OJ ( OJ ( 0) ( OJ ( OJ ( OJ ( OJ
0 0 0 0 0 0 0 0 0 0 osseous metaplasia 1 0 0 0 0 0 ( 0) ( OJ ( 0) ( OJ ( OJ 3J ( 0) ( OJ ( 0) ( OJ ( 0) ( OJ ( 0) ( 0) ( 0) ( 0)
0 0 0 0 2 0 0 0 1 0 bronchiolar-alveolar cell hyperplasta 1 0 0 0 0 0 ( OJ ( 4J ( OJ ( OJ 3J ( OJ ( OJ ( OJ ( OJ ( OJ ( OJ ( OJ ( OJ ( 7J ( OJ ( OJ
[l!ematcx:x:netlc sYstemJ
0 0 0 0 0 0 0 0 0 3 0 l:x:ne marrcxu grarl.llaticn 0 1 0 0 2 ( OJ ( 11J ( OJ ( OJ ( OJ OJ ( 3J ( OJ ( OJ ( 6J ( OJ ( OJ ( 0) ( OJ ( OJ ( OJ
.1' : p ;:;;i 0.05 ** ; p ~ 0.01 Test of Chi Square :Slisht : Hoelerate :t!arked :SevereSignificant difference ~
6
-
~
SfUDY NO. ; 0104 WI HAL : RAT F344 REPORT TYPE : Al SEX : HALE
Organ_ Findings
lllSfOLOG!CAL FlllDINGS ; NON-I!EOPLASfiC LESIONS (SUIIIIARY) SACRIFICED AI!IHALS (lOSW}
GrOUP Name Control 50 ppm
No. of Animals 37 34 (3) (4) (3) (%) (%) (%) (%) (%) (%) (%) (%)
(1)
(%)
200 ppm 30
(3) (%) (%)
(4)
(%) (!)
(%)
PAGE :
600 -28 (3) (4) (%) (%) (%)
2
Wemataxu eti c SYstem I
!:me manuw reticulosis
lYJ!d1 mde ectas1a of s1nus
0 0}
j
3}
(
(
0 0}
0 0}
(
(
0 01
0 0}
(
(
j
3}
0 Ol
(
(
0 0}
0 0}
(
(
0 0}
0 0)
(
(
0 0}
0 0}
(
(
0 0}
0 0}
(
(
0 0}
0 0}
(
(
0 0}
0 0}
(
(
0 0}
0 0}
(
(
0 01
0 0}
(
(
0 01
0 0}
(
(
0 01
0 0}
(
(
0 0}
0 0}
(
(
0 Ol
0 0}
thlolrus
g-aoolatic:n
l.ymphaden i tis
osseous metaplasia
0 OJ
2 51
1 3J
(
(
(
0 0}
0 0}
0 0}
(
(
(
0 O)
0 01
0 0}
(
(
(
0 OJ
0 0}
0 0}
(
(
(
0 0}
2 61
0 0}
(
(
(
0 0}
0 0}
0 0}
(
(
(
0 0}
0 0)
0 0}
(
(
(
0 0}
0 0)
0 OJ
0 ( 01
4 ( 13J
0 ( 0}
(
(
(
0 0}
0 0}
0 01
(
(
(
0 Ol
0 OJ
0 01
(
(
(
0 0)
0 OJ
0 0}
(
(
(
0 01
2 7J
0 0}
(
(
(
1 41
0 Ol
0 0}
(
(
(
0 0}
0 0}
0 0}
(
(
(
0 0}
0 OJ
0 Ol
SPleen deposit of hemosJderJn
granulation
4 ( 11J
1 3}
(
(
0 0}
0 0}
(
(
0 OJ
0 Ol
(
(
0 OJ
0 0}
(
(
3 9}
0 0}
(
(
0 0}
0 0}
(
(
0 0}
0 0}
(
(
0 0}
0 0}
(
(
2 71
0 01
(
(
0 0}
0 0}
(
(
0 01
0 01
(
(
0 01
0 0}
(
(
l 4}
0 0}
(
(
0 0}
0 0}
(
(
0 0}
0 OJ
(
(
0 01
0 01
fibrosiS
extramedullary hematopoJSSIS
2 5J
12 ( 32}
(
(
1 3}
l 3)
(
(
0 0)
0 0}
(
(
0 0}
0 OJ
0 ( OJ
5 ( 15}
(
(
0 0}
l 3}
(
(
0 OJ
0 0}
(
(
0 0}
0 0)
3 ( 10}
2 ( 7}
(
(
0 OJ
1 3J
(
(
0 0}
0 OJ
(
(
0 OJ
0 Ol
(
(
j
4}
1 41
(
(
0 0}
1 4}
(
(
0 0}
0 0}
(
(
0 0}
0 0}
[CirculatcrY sYStem]
heart throm!=
mmeralizatim
0 OJ
0 0}
(
(
0 Ol
0 0}
(
(
0 01
0 0}
(
(
0 OJ
0 0)
(
(
0 0}
1 31
(
(
0 01
0 0}
(
(
0 0}
0 01
(
(
0 01
0 01
(
(
0 OJ
0 0)
(
(
0 0}
0 Ol
(
(
0 Ol
0 01
(
(
0 Ol
0 01
(
(
l 4J
0 01
(
(
0 01
0 Ol
(
(
0 OJ
0 OJ
(
(
0 Ol
0 01
Significant difference ;
(IIPT150l
* ; p ;;; 0.05 u ; p ;;:,; 0.01 Test of au Square :Sli9ht : Moderate :Marked :Seuere
BA152
-
S1UDY NO. ' 0104 111SfOLOGICAL FINDINGS : NON-NEOPLASTIC LESIONS (SUHHARYJ
ANI HAL : RAT F344 SACRIFICED ANIMALS (105WJ REPGRT TYPE SEX
: Al : HALE PAGE : 3
GrOUP Name Control 50 ppm 200 ppm 600 ppm
No. of Ammals 37 34 30 28 (!) (1) (1) (2) (1)
Organ_ Findings (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%)
(Cirrutat!TY sYStem1
heart fil:rosiS l 3) (
0 O) (
0 0) (
0 OJ
0 ( OJ (
0 OJ (
0 OJ (
0 OJ
0 ( OJ (
0 0) (
0 OJ (
0 OJ
0 ( OJ (
0 OJ (
0 0) (
0 OJ
myocardial fibrosis 17 ( 46) (
0 OJ (
0 OJ (
0 OJ
20 ( 59) (
0 OJ (
0 OJ (
0 OJ
12 ( 40) (
1 3J (
0 OJ (
0 OJ
17 ( 61J (
0 OJ (
0 OJ (
0 0)
arteritis 1 3) (
0 OJ (
0 OJ (
0 0)
0 ( 0) (
0 0) (
0 0) (
0 0)
0 ( OJ (
0 OJ (
0 0) (
0 0)
0 ( 0) (
0 0) (
0 OJ (
0 OJ
arteryIsr:rt arteritis 3 8) (
0 0) (
0 0) (
0 0)
1 ( 3) (
0 0) (
0 0) (
0 0)
0 ( 0) (
0 0) (
0 OJ (
0 OJ
1 ( 4) (
0 OJ (
0 0) (
0 OJ
[Digestive system]
stOOlach mineralization 0 0) (
0 OJ (
0 OJ (
0 Dl
0 ( OJ (
1 3) (
0 0) (
0 OJ
0 ( OJ (
0 0) (
0 OJ (
0 0)
0 ( 0) (
0 Dl (
0 OJ (
0 OJ
utcer:farestomach 0 OJ (
l 3J (
0 OJ (
0 OJ (
1 3) (
l 3) (
0 OJ (
0 0) (
l 3) (
0 OJ (
0 0) (
0 OJ (
0 OJ (
l 4) (
0 OJ (
0 0)
hyperp las i a:fu-estomach 0 0) (
0 0) (
0 0) (
0 0) (
0 OJ (
1 3) (
0 OJ (
0 0) (
0 0) (
0 OJ (
0 0) (
0 OJ (
1 4) (
l 4) (
0 OJ (
0 OJ
erosJon:glandular stomach 2 5) (
0 OJ (
0 0) (
0 OJ (
0 0) (
0 OJ (
0 OJ (
0 OJ (
l 3) (
0 0) (
0 0) (
0 0) (
2 7) (
0 0) (
0 0) (
0 0)
utcer:gtandular stomach 0 0) (
0 0) (
0 OJ (
0 OJ (
2 6) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 OJ (
0 OJ (
0 0) (
0 OJ (
0 0) (
0 OJ
large mtes sranulatim 0 0) (
0 OJ (
0 OJ (
D D) (
0 0) (
0 0) (
0 0) (
0 OJ (
0 0) (
l 3) (
0 0) (
0 0) (
0 OJ (
0 O) (
0 OJ (
0 OJ
Liver herniation l 3) (
0 0) (
0 0) (
0 0) (
2 6) (
0 0) (
0 OJ (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
2 71 (
0 OJ (
0 OJ (
0 OJ
Sisnificant difference ; * : p ~ 0.05 u : I'~ 0.01 Test of Chi Square :Slisht :Uoderate :!iarked :Severe
(HPT150) BAIS2
"'
-
STUDY ND. ' 0104 IIISTOLOGICAL FINDINGS ; NON-NEOPLASTIC LESIONS (SUJINARYl
ANI HAL : RAT F344 SACRIFICED ANIMALS (I05W)
REPORT TYPE SEX
: AI ; HALE PAGE ;
4
~Nama Control 50 PPm 200 PPm 600 PPm
No. of Animals 37 34 30 28
Organ Findings (%)
(2) (%)
(%)
(%)
(%)
(%)
(%)
(%)
(%)
(%)
(%)
(%)
(%)
(%)
(3)
(%) (%)
{Digestive sYSteml
liver fatty change 0 0) (
0 0) (
0 0) (
0 0) (
1 3) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 OJ (
0 0)
srarulatioo 2 5) (
0 0) (
0 0) (
0 0) (
1 3J (
0 0) (
0 0) (
0 0)
1 ( 3) (
0 OJ (
0 0) (
0 0)
0 ( 0) (
0 0) (
0 0) (
0 0)
hyperp las i a 1 3) (
2 5) (
0 OJ (
0 0) (
1 3) (
0 OJ (
0 OJ (
0 OJ
3 ( IOJ (
2 7J (
0 OJ (
0 OJ
6 ( 21) (
1 4) (
1 4) (
0 OJ
clear cell focus 3 B) (
0 0) (
0 OJ (
0 0) (
1 3J (
0 Ol (
0 OJ (
0 OJ (
0 0) (
0 OJ (
0 0) (
0 0)
I ( 4) (
0 0) (
0 OJ (
0 0)
acfcb:lhi lie call focus 1 3J (
0 OJ (
0 0) (
0 0) (
0 0) (
0 OJ (
0 0) (
0 0) (
0 OJ (
0 0) (
0 0) (
0 0)
0 ( OJ (
0 0) (
0 0) (
0 0)
baSOPhi lie cell focus 4 ( Ill (
0 0) (
0 0) (
0 0) (
2 6) (
0 OJ (
0 0) (
0 OJ (
0 OJ (
0 0) (
0 0) (
0 OJ
3 ( 11) (
0 0) (
0 01 (
0 0)
vacuolated cell focus 0 OJ (
0 0) (
0 0) (
0 0) (
2 6) (
0 0) (
0 OJ (
0 0) (
1 3) (
0 OJ (
0 OJ (
0 0) (
0 0) (
0 OJ (
0 OJ (
0 OJ
m1xed cell focus 3 8) (
1 3) (
0 0) (
0 0) (
3 9) (
0 0) (
0 0) (
0 0) (
1 3) (
0 OJ (
0 OJ (
0 0) (
1 4J (
0 0) (
0 OJ (
0 0)
SPOnSiosis hepatis 5 ( 14J
0 ( 0) (
0 0) (
0 0)
4 ( 12) (
0 0) (
0 0) (
0 OJ
7 ( 23J (
1 3) (
0 OJ (
0 0)
11 ( 39J (
1 4) (
0 0) (
0 OJ
bile duct hYPerplasia 28 ( 76)
9 ( 24) (
0 0) (
0 0)
33 ( 97) (
J 3) (
0 0) (
0. 0)
30 (100) (
0 0) (
0 OJ (
0 0)
25 ( 89) (
2 7) (
0 0) (
0 OJ
pancreas atrwhY 9 ( 24)
2 ( 5) (
0 0) (
0 0)
8 ( 24) (
J 3) (
0 0) (
0 0)
5 ( 17J (
0 OJ (
0 OJ (
0 OJ
4 ( 14J (
0 0) (
0 OJ (
0 0)
hyperplasJa!acinar cell 0 ( 0)
0 ( OJ (
0 OJ (
0 OJ
0 ( OJ (
0 OJ (
0 OJ (
0 0)
J ( 3J (
0 OJ (
0 OJ (
0 OJ
0 ( 0) (
0 OJ (
0 OJ (
0 OJ
Siroificant difference ' * ; p ~ 0.05 *::s: ; p :iii 0.01 Test of Oli Square (!):Slight :}!oderate :Marked :Severe
(IIPT150J BAIS2
w
-
STUDY liD. ' 0104 lllSTOLOGlCAL FINDINGS : NON-NEOPLASTIC LESIOIIS (SUIIIIARYJ
All!HAL : RAT F344 SACRIFICED ANHIALS (10511) REPORT TYPE SEX
: :
AI HALE PAGE 5
Group Name No. of ilmmals
(1)
Control 37
(3) (4) (j)
50 ppm 34
(4) (j)
200 ppm 30
(4) (1)
600 ppm 28
(3) Orsan__ Findings (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%)
[Urmary SYStem!
kicheY hyperplasJa:tubular epithelial call 0 0)
0 ( 0)
0 ( OJ
0 ( 0)
0 ( 0) (
0 0)
0 ( 0)
0 ( 0)
0 ( 0)
0 ( 0)
0 ( 0)
0 ( OJ
l ( 4)
0 ( 0)
0 ( OJ
0 ( OJ
atypical tl..bular di latation:prm:Jmal tul:ule 0 OJ
0 ( 0)
0 ( 0)
0 ( OJ
0 ( 0) (
0 0)
0 ( 0)
0 ( 0)
0 ( 0)
0 ( OJ
0 ( 0)
0 ( 0)
14 ( 50)
4 ( 14J
0 ( 0)
0 ( OJ
ctrcn1 c neph-opathY 1 3J
7 ( 19J
17 ( 46J
12 ( 32J
3 ( 9) (
3 9)
13 ( 38)
14 ( 41)
0 ( OJ
3 ( 10)
18 ( 60)
9 ( 30)
0 ( 0)
0 ( 0)
8 ( 29)
20 u ( 71)
hYchneplTos1s 0 0)
0 ( 0)
0 ( OJ
0 ( OJ
0 ( OJ (
0 OJ
0 ( OJ
0 ( 0)
l ( 3J
0 ( 0)
0 ( OJ
0 ( 0)
0 ( OJ
0 ( OJ
0 ( Ol
0 ( OJ
renal dysgenesis 1 3J
0 ( 0)
0 ( 0)
0 ( 0)
0 ( O) (
0 0)
0 ( 0)
0 ( OJ
0 ( OJ
0 ( OJ
0 ( OJ
0 ( 0)
0 ( 0)
0 ( OJ
0 ( 0)
0 ( 0)
nuclear entarsement:proximal tubule 0 0)
0 ( OJ
0 ( OJ
0 ( 0)
0 ( 0) (
0 0)
0 ( 0)
0 ( 0)
18 ( 60)
0 ( OJ
0 ( OJ
0 ( OJ
2 ( 7J
26 ( 93J
0 ( OJ
o .. ( 0)
Lrln bladd inflanvnatorY cell nest 0 OJ
0 ( OJ
0 ( OJ
0 ( OJ
0 ( 0) (
l 3J
0 ( OJ
0 ( OJ
0 ( OJ
0 ( OJ
0 ( 0)
0 ( OJ
0 ( 0)
0 ( 0)
0 ( OJ
0 ( OJ
{Encbcnne sYStemJ
pituftarY cYSt 3 8)
0 ( OJ
0 ( 0)
0 ( OJ
0 ( 0) (
0 0)
0 ( 0)
0 ( 0)
3 ( 10)
0 ( OJ
0 ( 0)
0 ( OJ
3 ( 11)
0 ( 0)
0 ( 0)
0 ( 0)
hYPerplasia 9 ( 24)
l ( 3)
0 ( OJ
0 ( OJ
7 ( 211 (
l 3J
0 ( Ol
0 ( 0)
7 ( 231
l ( 3J
0 ( 0)
0 ( OJ
5 ( 181
0 ( 01
0 ( OJ
0 ( 0)
Rathke POUch l 31
0 ( 01
0 ( OJ
0 ( 0)
0 ( Ol (
0 OJ
0 ( OJ
0 ( 0)
l ( 3)
0 ( OJ
0 ( Ol
0 ( 01
l ( 4)
0 ( 0)
0 ( 0)
0 ( 0)
thmlld ultlmibranctual body remanet 0 OJ
0 ( O)
0 ( OJ
0 ( Ol
1 ( 3) (
0 0)
0 ( OJ
0 ( 0)
0 ( OJ
0 ( 0)
0 ( 0)
0 ( 0)
0 ( Ol
0 ( OJ
0 ( 0)
0 ( 01
Si91ificant difference ; :P;ii0.05 ** ! p ;;;;; 0.01 Test of Q-u SQ.Jare (l):Sli9ht : Hoderate :Uarked :Seuere
(IIPT150) BAIS2
._\
http::P;ii0.05
-
Co
STUDY NO. ' 0104 ANIMAL ' RAT F344 REPORT TYPE ; Al SEX : HALE
HISTOLOGICAL FINDINGS ' NON-NEOPLASTIC LESIONS SACRIFICED ANIMALS (105M)
(SUMMARY!
PACE ; 6
Q-gan Findings
Group Name No. of Antmats
(1)
(%)
Control 37
-
STUDY NO. : OI04 HISTOLOGICAL FINDINGS : NOll-NEOPLASTIC LESIOIIS (SUMMARY)
ANI HAL : RAT F344 SACRIFICED ANIMALS (lOSWl REPORT TYPE SEX
: :
AI MALE PAGE : 7
GrOUP Name Ccrltrol 50 ppm 200 ppm 600 PPm No. of Ammals 37 34 30 28
Organ__ Findings (!)
(%) (%)
(3> (%)
(%)
(%)
(%)
(%)
(%)
(!)
(%) (%)
(%)
(%)
(!)
(%) (%)
(%)
(%)
(Reproj.J(:tlve SYStem}
~tate hYPerplasia 10 ( 27) (
0 0) (
0 OJ (
0 0)
6 ( I8J (
0 OJ (
0 OJ (
0 0)
6 ( 20) (
0 OJ (
0 OJ (
0 0)
6 ( 21J (
0 OJ (
0 OJ (
0 0)
(Nen.rus SYStem]
brain hYa li ne l:ody 11 ( 30J (
0 OJ (
0 OJ (
0 0)
7 ( 2ll (
0 OJ (
0 OJ (
0 0)
8 ( 27) (
0 OJ (
0 0) (
0 0)
6 ( 2ll (
0 OJ (
0 0) (
0 OJ
(Special sense organs/appandagej
eye cataract j 3J (
j
3J ( 0 OJ (
0 OJ (
j
3J ( 0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ
retinal atrOPhy 0 Ol (
0 OJ (
j
3J ( 0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 0) (
j
4) ( 0 0) (
0 OJ
keratitis 0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 0) (
j
3J ( 0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 0) (
0 O) (
0 OJ (
0 OJ (
0 OJ (
0 OJ
degeneration:cornea j 3J (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ (
0 OJ
Harder sl inflafMlatlon 0 0) (
0 OJ (
0 0 OJ ( OJ (
j j 0 3J ( 3J ( OJ (
0 OJ
0 ( OJ (
0 OJ
0 0 ( OJ ( 0) (
0 OJ (
0 OJ (
0 OJ (
0 OJ
[Musculoskeletal s>'StemJ
ll'IJScle necrosis 0 OJ (
0 0) (
0 0 OJ ( OJ (
j 0 0 3J ( OJ ( OJ (
0 OJ
0 ( OJ (
0 OJ
0 0 ( OJ ( OJ (
0 OJ (
0 0) (
0 OJ (
0 OJ
l:ooe hYPerplasia 0 0) (
0 OJ (
0 0 OJ ( OJ (
0 0 0 0) ( 0) ( OJ (
0 OJ
l ( 3J (
0 OJ
0 0 ( OJ ( 0) (
0 OJ (
0 OJ (
0 OJ (
0 OJ
Sisnlficant difference ; *'~P:;i0.05 ** : ? ;;;;;: 0.01 Test of Q-u Square
-
" STUDY NO. ANI HAL REPORT TYPE SEX
' 0104 : RAT F344 : AI : HALE
IIISTOLOGICAL FINDINGS : NON-NEOPLASTIC LESIONS SACRIFICED AIIIHALS (!05Wl
(SUIIUARY)
PAGE , 8
Organ_ Findings
GrcJLP Name No. of Animals
(!)
(%)
Control 37
(%) (%)
(%)
(!)
(%)
50 PDlll 34
(%) (%)
(%)
(])
(%)
200 PDlll 30
(%) (%)
(%)
(!)
(%)
600 P~> 28
(%) (%)
(%)
[Musruloskeletal SYsteml
OCne osteosclerosis 0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
j
4) ( 0 0) (
0 0) (
0 0)
(Body cavities!
adiPOSe granulation 0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
2 7) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0) (
0 0)
Si11ificant difference ;
(UPT!50)
"" : p ;:;i 0.05 ** ; p ;:;;; 0.01 Test of Chi Square :Slisht :Moderate :Uarked :Severe
BAIS2
-
APPENDIX L 4
HISTOLOGICAL FINDINGS NON-NEOPLASTIC LESIONS
(TWO-YEAR STUDIES:SUMMARY)
RAT:FEMALE:SACRIFICED ANIMALS
-
STUDY NO. ' 0104 IIISTOLOGICAL FlllDINGS : NON-l/EOPLASTIC LESIOJIS (SUllliARYl
ANI HAL : RAT F344 SACRIFICED AlllliALS (10511)
REPORT TYPE : A1 PAGE ' 9SEX ' FE!!ALE
ppmGroup llama Control 50 ppm 200 ppm 600
34 34No. of Ammals 42 34 (!) (4) (!) {!) (3) (3)
IJrgan__ Findings (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%)
{ReSPiratorY SYStem] 0 00 0 0 0 0 0 0 0 2 0 0 0 0 0nasal cavit tln:JirDus
OJ ( OJ ( OJ ( 0) ( 0} ( OJ ( OJ ( 0} ( 6J ( 0} ( 0) ( 0) ( 0) ( 0) ( 0) ( OJ
4 9 9 0 4 12 8 3 8 15 4 1 7 9 4 0eosinophilic change:otfactory epithelium OJ ( 12} ( 35) ( 24J ( 9) ( 24J ( 44) ( 12) ( 3J ( 21) ( 26) ( 12) ( 0)( 10) ( 21) ( 21) (
0 2 0 0eos1nJDhi lie change:respiratorY epitheliun 19 7 0 0 14 10 3 0 28 1 0
16
( 45J ( 17) ( 0) ( 0) ( 41) ( 29) ( 9J ( 0) ( 82) ( 3) ( Ol ( OJ ( 47J ( 6) ( 0) ( OJ
4 9 0 0 5 2 1 0 10 1 0 0. 6 0 0 0
mflarrmation:foreJgn body ( 10) ( 21) ( OJ ( OJ ( 15) ( 6J ( 3) ( 0) ( 29) ( 3) ( 0) ( OJ ( 18J ( 0) ( OJ ( 0)
0 0 0 0llll9 he!OOIThage 1 0 0 0 0 0 0 0 0
0 0 0 ( 0) ( 0) ( 0) ( OJ ( 0) ( 0) ( 0} ( 0}2) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0) ( 0)
0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0
bronchiolar-alveolar cell hYPerplasia ( 6) ( OJ ( OJ ( 0}OJ ( OJ ( 0) ( 0) ( OJ ( 0} ( 0} ( 0) ( 0) ( 0) ( 0) ( 0)
(l!ematOPQJetic SYstemJ
4 0 0 0 7 0 0 0bene rna!TOJJ grarulation 3 0 0 0 4 1 0 0
7} ( 0} ( O) ( 0} ( 12} ( 3} ( OJ ( OJ ( 12} ( OJ ( 0) ( 0) ( 21) ( 0} ( OJ ( 0}
0 0 0 0 1 0 0 0reticulosis 0 0 0 1 0 0 0 0 0) ( 3} ( OJ ( OJ ( 0)0} ( 0) ( O) ( 2} ( 0} ( 0) ( OJ ( 0} ( 0} ( OJ ( OJ (
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
lYil
-
~
HISTOLOGICAL FINDINGS NON-IIEOPLAST!C LESIONS (SUMHARYl STUDY NO. ' 0104 ANIMAL : RAT F344 SACRIFICED ANillALS (105WJ
REPORT TYPE : A1 PAGE 10SEX : FEHALE
Group Name Control 50 600 PPm 200 ppm PPm34 34 No. of Animals 42 34
(4) (l) (3) (4)(2)
-
" STUDY NO. : 0104 ANI HAL : RAT F344 REPORT TYPE : AI SEX : FEHALE
HISTOLOGICAL FlliOINGS : NON-liEOPLASTIC LESIONS SACRIFICED Ali!HALS (10511)
(SUHHARYl
PAGE : 11
Organ__ Findinss
Group Nama No. of Ammals
(!)
(%)
Control 42
(%) (%)
(4)
(%) (!)
(%)
50 ppm 34
(3) (%) (%)
(%)
(%)
200 ppm 34
(2) (3) (%) (%)
(4)
(%) (%)
600 ppm 34
(%) (%)
(%)
[Digestive SYStem!
stanach erosicn:glandular stomach
liver hem1aticn
necrosls:focaL
granulation
hyperplasia
clear cell focus
baSOPhilic cell focus
vaCt..Olated cell focus
mixed cell focus
bile duct hyperplasia
pancreas atrc:OOY
hyperp las1a: acinar cell
0 OJ (
4 ( !0) (
0 ( OJ (
7 ( 17) (
0 OJ (
1 2J (
0 01 (
0 01 (
2 5) (
5 ( 12) (
4 ( !OJ (
0 ( OJ (
0 0)
0 0)
0 0)
3 7)
0 OJ
0 0)
0 0)
0 0)
0 0)
0 0)
1 2)
0 OJ
(
(
(
(
(
(
(
(
(
(
(
(
0 OJ
0 0)
0 0)
1 2)
0 0)
0 0)
0 0)
0 0)
0 OJ
0 0)
0 OJ
0 0)
(
(
(
(
(
(
(
(
(
(
(
(
0 OJ
0 0)
0 0)
0 OJ
0 0)
0 0)
0 OJ
0 01
0 OJ
0 0)
0 0)
0 OJ
0 ( OJ
3 ( 9)
0 ( 0)
6 ( 181
0 ( 0)
0 ( OJ
1 ( 31
0 ( 0)
1 ( 3)
5 ( !51
2 ( 6)
0 ( 0)
(
(
(
(
(
(
(
(
(
(
(
(
0 0)
0 0)
0 0)
1 3)
0 0)
0 0)
0 0)
0 0)
0 OJ
0 0)
0 0)
0 OJ
(
(
(
(
(
(
(
(
(
(
(
(
0 OJ
0 OJ
0 OJ
0 0)
0 OJ
0 OJ
0 0)
0 0)
0 0)
0 OJ
0 0)
0 0)
(
(
(
(
(
(
(
(
(
(
(
(
0 OJ
0 OJ
0 0)
0 0)
0 OJ
0 0)
0 0)
0 0)
0 0)
0 0)
0 0)
0 0)
0 ( 0)
0 ( 0)
1 ( 3)
13 ( 38)
1 ( 3J
0 ( 0)
2 ( 6)
0 ( 0)
2 ( 6J
6 ( !8J
1 ( 3)
0 ( OJ
(
(
(
(
(
(
(
(
(
(
(
(
1 3)
0 0)
0 0)
1 3)
0 OJ
0 0)
0 0)
0 0)
0 0)
1 3J
0 OJ
0 OJ
(
(
(
(
(
(
(
(
(
(
(
(
0 0)
0 OJ
0 OJ
0 0)
0 0)
0 0)
0 0)
0 0)
0 0)
0 0)
0 OJ
0 0)
(
(
(
(
(
(
(
(
(
(
(
(
0 OJ
0 OJ
0 OJ
0 0)
0 0)
0 OJ
0 0)
0 01
0 0)
0 OJ
0 0)
0 0)
0 ( 0)
3 ( 9J
0 ( OJ
7 ( 21)
1 ( 3)
1 ( 3)
0 ( OJ
1 ( 3)
0 ( 0)
11 ( 32)
2 ( 6J
1 ( 3)
(
(
(
(
(
(
(
(
(
(
(
(
0 0)
0 OJ
0 0)
3 9)
0 0)
0 OJ
0 0)
1 3)
0 0)
0 OJ
0 OJ
0 OJ
(
(
(
(
(
(
(
(
(
(
(
(
0 OJ
0 OJ
0 OJ
0 0)
0 0)
0 0)
0 OJ
0 0)
0 0)
0 0)
0 OJ
0 OJ
(
(
(
(
(
(
(
(
(
(
(
(
0 OJ
0 0)
0 0)
0 0)
0 0)
0 0)
0 OJ
0 0)
0 OJ
0 OJ
0 OJ
0 0)
Significant difference
(HPT!50J
: : p ::; 0.05 u ; p & 0.01 Test of Ch1 Square
-
SfUDY ND. : 0104 IIJSTOLOG1CAL FINDINGS : !ION-NEOPLASTIC LESIONS (SUMMARY)
ANI HAL : RAT F344 SACRIFICED AHHIALS (!0511) REPORT TYPE SEX
: A1 : FEMALE PAGE : I2
GrOUP Name Control 50 - 200 - 600 ppm No. of Animals
42 (2) (3)
34 (3) (4) (1)
34 (3) (4) (1)
34 (2) (4)
Organ__ Findill9S (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%)
[Unnary system]
kichey hYPerplasta:tubular epithelial cell 0 0)
0 0 ( 0) ( OJ
0 ( 0)
0 ( OJ
0 0 ( 0) ( 0) (
0 OJ
1 ( 3J
0 0 ( 0) ( 0) (
0 0)
0 ( OJ
0 0 ( 0) ( 0) (
0 0)
mineralizatim I 2J
0 0 ( 0) ( 0)
0 ( 0)
0 ( 0)
0 0 ( OJ ( 0) (
0 OJ
0 ( 0)
0 0 ( OJ ( 0) (
0 OJ
0 ( OJ
0 0 ( 0) ( OJ (
0 OJ
dTmic nep!"ropathy I2 ( 29)
17 5 ( 40J ( 12J
4 ( 10J
12 ( 35J
13 5 ( 38) ( 15) (
2 6J
11 ( 32)
13 6 ( 38) ( 18J (
3 9J
11 ( 32J
I2 6 ( 35J ( 18J (
3 9)
nuclear enlargement:proxJmal tubule 0 ( 0) (
0 0) (
0 0) (
0 OJ
0 ( 0) (
0 OJ (
0 OJ (
0 0)
1 ( 3) (
0 OJ (
0 OJ (
0 0)
14 ( 4ll (
0 0) (
0 OJ (
0 0)
[Endcx:rine SYsteml
pituitary cYSt 7 ( 17) (
1 2) (
0 0) (
0 OJ
5 ( 15) (
1 3J (
0 0) (
0 0)
7 ( 21J (
0 OJ (
0 0) (
0 0)
10 ( 29) (
3 9) (
0 OJ (
0 0)
hYPerplasia 11 ( 26) (
2 5) (
0 OJ (
0 OJ
5 ( 15) (
1 3J (
0 0) (
0 0)
8 ( 24J (
0 OJ (
0 OJ (
0 OJ
7 ( 2ll (
0 OJ (
0 OJ (
0 0)
RatH
-
' (SUMMARY) STUDY NO. : NON-NEOPLASTIC LESIONS ' 0104 lllSTOLOG1CAL FINDINGS
ANIMAL : RAT F344 SACRIFICED All!HALS (!OSW)
REPORT TYPE : AI PAGE : 13
SEX : FEHALE
200 ppm 600 ppm GrOUP Name Control 50 DPil1 34 34 No. of Animals 42 34
(%) (%) (%) (%) (%) (%) (%) (%) (%) Organ_ (%) (%) Findings (%) (%) (%) (%) (%)
(81cb::rine system I 0 0 0 0 2 0 0 0 2 l 0 0 ad-enal hyperplasia:cortical cell l l 0 0
( 3J ( OJ ( OJ ( 0) ( OJ ( OJ ( OJ ( 2J ( 2J ( OJ ( 0) ( 6J ( OJ ( 0) ( OJ ( 6)
0 0 0 0 0 0 l 0 0 0 2 0 hYPerplasl a:medulla 2 0 0 0 ( 6J ( OJ ( 0) ( OJ 5) ( 01 ( 01 ( 0) ( OJ ( 0) ( 0) ( 0) ( 3J ( OJ ( OJ ( OJ
0 0 0 0 0 0 0 0 0 0 0 accesory cortical nodule 0 0 0 0 l ( 0) ( OJ ( OJ ( OJ ( Ol ( O) OJ ( OJ ( OJ ( OJ ( 3J ( OJ ( OJ ( OJ ( OJ ( OJ
0 0 0 0 4 0 0 0 8 0 focal fattY change: cortex 5 0 0 0 4 0 ( 0) ( OJ ( 24J ( 0) ( OJ ( OJ ( 12J ( 0) ( 01 ( OJ ( 12J ( 0) ( OJ ( 0) ( 12J ( OJ
[Reproci.Jctive SYSteml
7 l 0 0 0 4 l 0 0 5 2 0 0 uterus CYSt ic endometn aL hYPerp las 1a 2 3 0 ( OJ ( OJ ( 21 J ( 3J ( 01 ( OJ 5J ( 71 ( OJ ( 0) ( 12J ( 3J ( 0) ( OJ ( 15) ( 6J
0 0 0 l 0 0 0 l 0 0 0 mamnary gl duct aetas i a l 0 0 0 l ( 01 ( OJ ( 01 ( OJ ( 01 ( 01 2J ( OJ ( 0) ( 0) ( 3J ( 3J ( 0) ( OJ ( 01 ( 3J
0 0 0 0 0 0 l 0 0 0 0 hyperplasia 0 0 0 0 0 ( 01 ( OJ ( OJ ( OJ ( OJ ( OJ 01 ( OJ ( 01 ( 01 ( 01 ( 01 ( 01 ( OJ ( 31 ( OJ
(NeruJUS SYStem]
2 0 0 0 0 0 0 l 0 0 0 l 0 0 !:rain hemcrrhage 2 0 ( OJ ( OJ ( 6) ( OJ ( OJ ( OJ 51 ( OJ ( OJ ( 0) ( 3J ( OJ ( 0) ( OJ ( 3J ( OJ
0 0 0 0 0 0 0 0 0 0 0 1 mineralization 0 0 0 0 ( 01 ( 01 ( 31 ( 01 ( OJ ( 01 OJ ( 01 ( 01 ( 01 ( 01 ( OJ ( OJ ( 01 ( 01 ( OJ
8 0 0 0 16 0 0 0 10 0 0 0 hYaline l::ody 16 0 0 0 0) ( OJ ( 24) ( OJ ( 01 ( 0) ( 38) ( 0) ( 01 ( 0) ( 471 ( 01 ( OJ ( OJ ( 29) ( OJ (
:Slight : Moderate :Harked :Severe Sig1ificant difference ; ~ : p :;;; 0.05 n : P ;;i 0.01 Test of Chi Souare
8A1S2 (IIPT1501
-
STUDY NO. ' 0104 IIISTDLDGICAL FINDINGS ' !ION-NEOPLASTIC LESIONS (SUHHARYlANI HAL ' RAT F344 SACRIFICED ANIMALS (!05Wl REPORT TYPE : A! SEX ' FEHALE PAGE ' 14
Group llama Control 50 PPm 200 PPm 600 PPm
No. of Animals 42 34 34 34 (!) (!) (3) (!) (!)
Organ_ Findings (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%)
{Special sensa O"'gans/appandagej
6Y6 cataract 2 5) (
0 0) (
0 0 0) ( 0) (
0 0 0 Ol ( 0) ( OJ (
0 Ol
0 ( 0) (
0 0 0 0) ( 0) ( 0) (
2 6) (
0 0) (
1 3) (
0 0)
retinal atrophy 0 Ol (
0 OJ (
2 0 5) ( OJ (
0 0 0 OJ ( OJ ( OJ (
0 0)
0 ( 0) (
1 0 0 3) ( OJ ( 0) (
0 0) (
1 3) (
3 9J (
0 0)
daseneration:cornea 1 2) (
0 0) (
0 0 0) ( 0) (
3 0 0 9) ( 0) ( 0) (
0 0)
l ( 3) (
0 0 0 OJ ( 0) ( 0) (
2 6) (
0 0) (
0 0) (
0 0)
hawDrrhasa:retina 0 OJ (
0 OJ (
0 0 0) ( OJ (
0 0 0 0) ( 0) ( OJ (
0 0)
1 ( 3) (
0 0 0 0) ( 0) ( 0) (
0 0) (
0 0) (
0 0) (
0 OJ
!larder sl desenerat ioo 0 0) (
0 0) (
0 0 0) ( 0) (
0 0 0 0) ( 0) ( 0) (
0 0)
0 ( 0) (
2 0 0 6J ( 0) ( OJ (
0 OJ (
0 0) (
0 0) (
0 OJ
1nflarrmaticn 0 OJ (
0 0) (
0 0 0) ( 0) (
1 1 0 3) ( 3J ( 0) (
0 0)
0 ( OJ (
0 0 0 0) ( 0) ( 0) (
0 0) (
0 0) (
0 0) (
0 0)
sranulatioo 0 OJ (
0 OJ (
0 0 0) ( OJ (
0 0 0 0) ( 0) ( 0) (
0 0)
0 ( 0) (
0 0 0 0) ( 0) ( 0) (
1 3) (
0 0) (
0 0) (
0 0)
[Husculoskeletal SySteml
b
-
APPENDIX L 5
HISTOLOGICAL FINDINGS :NON-NEOPLASTIC LESIONS
(TWO-YEAR STUDIES:SUMMARYJ
MOUSE:MALE:DEAD AND MORIBUND ANIMALS
-
STUDY NO. ; 0105 HISTOLOGICAL FINDHIGS : 11011-l!EOPLAST!C LESIONS (SUMMARY)
ANIMAL ; HOUSE BDF1 DEAD AND MORIBUND ANIMALS (0-10511)
REPORT TYPE ; A1 SEX : MALE
PAGE ;
Organ__ Findings
Group Nama No. of Ammals
(%)
Ccrrtrol 19
(2) (%) (%)
(4)
(%) (!)
(%)
10 15 -
(3) (%) (%)
(4)
(%)
so ppm 22
(!) (3) (%) (%) (%)
(4)
(%) (%)
2SO ppm 28
(3) (%) (%)
(%)
{ I nte9Jli8fltary sYStem/appandaga J
skln/app 1nf lamnat ien l 5)
0 0 ( OJ ( OJ (
0 0)
0 ( OJ
0 l ( OJ ( 7) (
0 0)
0 l 0 ( OJ ( 5) ( 0) (
0 OJ
l ( 4J
l 0 ( 4) ( 0)
0 ( OJ
abscess 0 OJ
0 0 ( 0) ( OJ (
0 OJ
0 ( OJ
0 0 ( OJ ( OJ (
0 O)
0 0 0 ( OJ ( OJ ( 0) (
0 OJ
0 ( OJ
l 0 ( 4J ( OJ
0 ( OJ
SLtx::utis inftafMlation 0 0)
0 0 ( 0) ( 0) (
0 0)
0 ( OJ
l 0 ( 7) ( OJ (
0 OJ
0 2 0 ( 0) ( 9) ( 0) (
0 0)
0 ( 0)
0 l ( 0) ( 4)
0 ( 0)
[Respirata'Y system]
nasal cavit aches ion 0 OJ
0 0 ( OJ ( 0) (
0 OJ
0 ( OJ
0 0 ( OJ ( OJ (
0 OJ
0 0 0 ( 0) ( OJ ( OJ (
0 OJ
0 ( OJ
l 0 ( 4) ( OJ
0 ( OJ
hemorrhage 0 OJ
0 l ( 0) ( 5) (
0 0)
0 ( 0)
0 0 ( 0) ( 0) (
0 0)
0 0 0 ( 0) ( 0) ( 0) (
0 0)
0 ( 0)
l 0 ( 4) ( 0)
0 ( 0)
eosi!iOPhi lie change:olfactorY epithaliun 4 ( 21)
0 0 ( OJ ( OJ (
0 0)
2 ( 13)
0 0 ( OJ ( 0) (
0 OJ
l 0 0 ( 5) ( 0) ( 0) (
0 0)
0 ( 0)
0 0 ( OJ ( OJ
0. ( OJ
eosiOOPhi lie changa:respwatorY epitheliun 2 ( 11)
0 0 ( OJ ( OJ (
0 0)
l ( 7)
0 0 ( 0) ( 0) (
0 0)
l 0 0 ( 5J ( OJ ( OJ (
0 OJ
l ( 4J
0 0 ( OJ ( OJ
0 ( OJ
respiratorY metaplasta:olfactory epithelium 6 ( 32)
0 0 ( OJ ( OJ (
0 0)
6 ( 40)
0 0 ( 0) ( 0) (
0 0)
4 0 0 ( 18) ( OJ ( OJ (
0 OJ
5 ( 18)
l 0 ( 4) ( 0)
0 ( 0)
reSPiratorY metaplasta:stand 8 ( 42J
5 0 ( 26) ( 0) (
0 0)
6 ( 40)
3 0 ( 20) ( 0) (
0 0)
6 3 0 ( 27) ( 14) ( 0) (
0 0)
9 ( 32)
2 0 ( 7) ( 0)
0 ( OJ
na=harY!t< eosinophilic change 0 OJ
0 0 ( OJ ( 0) (
0 OJ
l ( 7)
0 0 ( OJ ( 0) (
0 0)
0 0 0 ( 0) ( 0) ( 0) (
0 0)
0 ( OJ
l 0 ( 4J ( OJ
0 ( 0)
larYnX LYIN'hocY'tic mfi Ltration 0 0)
0 0 ( 0) ( 0) (
0 0)
0 ( 0)
l 0 ( 7) ( 0) (
0 0)
0 0 0 ( 0) ( OJ ( 0) (
0 0)
0 ( 0)
0 0 ( OJ ( 0)
0 ( 0)
Significant difference : ~;P:;!0.05 n : P ;:;;; 0.01 Test of Cht SQ.Jare (!):Slight : Moderate :Marked :Seuere
BAIS2 (IIPT150)
"
-
.~
STUDY 110. ANIMAL REPORT TYPE SEX
: 0105 : MOUSE BDFI : AI ; HALE
IIISTOLOG!CAL FINDINGS : NON-NEOPLASTIC LESIONS DEAD AND HDR!BUIID ANIMALS (0-!0511)
(SUMMARY)
PAGE : 2
IJrgan__ Findings
Group Name No. of Animals
(%)
Control 19
(3) (%) (%)
(4)
(%) (%)
10 ppm 15
(%) (%)
(4)
(%) (%)
50 ppm 22
(2) (%) (%)
(4)
(%) (%)
250 ppm 2B
(3) (%) (%)
(4)
(%)
(Resplrata*Y sYStem}
LU19 cmgestion
herrorrhage
edema
mflarrrnation
lYmPhocY'tic mfi ltration
l::n:nchlalar-alueolar call hYPerplasia
0 01
0 0)
0 0)
0 0)
0 0)
0 0)
2 ( Ill
0 ( 0)
0 ( 01
I ( 5)
0 ( 0)
0 ( 0)
(
(
(
(
(
(
0 0)
0 0)
1 51
0 0)
0 0)
0 0)
(
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
0 01
0 0)
(
(
(
(
(
(
1 7)
0 0)
0 01
0 0)
0 0)
0 0)
(
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
1 7)
0 0)
(
(
(
(
(
(
0 0)
0 01
0 Ol
0 0)
0 0)
0 0)
(
(
(
(
(
(
0 0)
0 01
0 01
0 0)
0 01
0 0)
(
(
(
(
(
(
0 0)
0 0)
0 01
0 0)
0 0)
0 0)
(
(
(
(
(
(
0 0)
0 0)
0 0)
0 01
0 0)
0 0)
(
(
(
(
(
(
0 0)
0 0)
0 01
0 0)
0 0)
0 0)
(
(
(
(
(
(
0 01
0 0)
0 01
0 0)
0 0)
0 0)
(
(
(
(
(
(
0 Ol
2 7)
0 0)
0 0)
1 41
0 0)
(
(
(
(
(
(
1 41
0 0)
0 0)
0 0)
0 0)
0 0)
(
(
(
(
(
(
0 0)
0 0)
1 4)
0 0)
0 0)
1 41
(
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
0 0)
0 0)
[l!emata:x:netic sYSteml
l:xne marrow vascular
mye laf i l:ros1s
L""*> rode dePOSit of hemosJder1n
tll)'lli.JS atrophy
SPleen atrophy
0 0) (
0 0) (
3 ( !6) (
0 0) (
0 0) (
0 0)
0 0)
0 0)
0 0)
0 0)
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
0 0)
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
0 0)
0 ( 0)
0 ( 0)
3 ( 20)
0 ( 0)
I ( 7)
(
(
(
(
(
0 0)
0 0)
I 71
0 0)
0 0)
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
0 0)
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
0 0)
1 ( 5)
0 ( 0)
3 ( 141
0 ( 0)
0 c o1
(
(
(
(
c
0 0)
1 5)
I 51
I 5)
0 o1
(
(
(
(
c
0 0)
0 01
0 0)
0 0)
0 o1
(
(
(
(
<
0 01
0 0)
0 0)
0 0)
0 or
0 ( 0)
0 ( 0)
11 ( 39)
0 ( 0)
0 ( 0)
(
(
(
(
(
0 01
0 0)
2 7)
0 0)
2 71
(
(
(
(
(
0 0)
0 0)
0 0)
0 0)
0 0)
(
(
(
(
(
0 0)
0 01
0 0)
0 0)
0 0)
Sisnificant difference ;
(HPTI50)
* : p s 0.05 n ; P ;;:;:; 0.01 Test of Ch1 SQUare (l>:Slisht : Moderate :Marked :Severe
BAIS2
-
STUDY ND. ' 0105 IIISTDLOG1GAL FINDINGS ' IIDII-NEOPLASTIG LESIONS (SUHIIARY) ANI HAL ' HOUSE BDF1 DEAD AND IIDRIBUND AIIII!ALS (0-1051iJ REPORT TYPE SEX
' '
AI HALE PAGE ' 3
Gro..p Nama No. of Animals
Control l9
10 ppm 15
50 ppm 22
250 ppm 28
(!)
-
STUDY NO. : 0!05 HISTOLOGICAL FINDINGS ; 11011-NEOPLASTIC LESIONS (SUIIIIARYJ All! HAL : MOUSE BDF! OEAB AIIB NORIBUND AIIIIIALS (0-!05WJ REPORT TYPE SEX
: A! : HALE PAGE ; 4
Grot.JD Name Control 10 ppm 50 ppm 250 ppm
No. of Ammals 19 15 22 28 (!) {!) (!) {3) (4) (!)
Or-san__ Findings (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%)
[CirculatcrY SYstem]
arteryIacrt arteritis 0 OJ (
1 5J (
0 0 OJ ( D)
0 0 0 ( OJ ( OJ ( OJ (
0 OJ
0 ( OJ
l 0 0 ( 5) ( OJ ( OJ
0 0 ( 0) ( OJ
0 ( OJ (
0 0)
[Disestiue SYStemj
tooth mflarrmaticn 1 5) (
0 OJ (
0 0 OJ ( 0)
0 0 0 ( OJ ( OJ ( OJ (
0 OJ
1 ( 5)
0 0 0 ( OJ ( OJ ( 0)
0 0 ( OJ ( 0)
0 ( OJ (
0 OJ
dySPlasia 7 ( 37) (
l 5) (
0 0 0) ( OJ
3 l l ( 20) ( 7J ( 7J (
0 0)
8 ( 36J
l l 0 ( 5) ( 5J ( 0)
5 0 ( !8J ( OJ
0 ( 0) (
0 0)
tm;ua arteritis 0 ( OJ (
l 5) (
l 0 5) ( OJ
0 0 0 ( OJ ( 0) ( OJ (
0 0)
0 ( 0)
l 0 0 ( 5) ( OJ ( 0)
0 0 ( 0) ( 0)
0 ( 0) (
0 0)
stonach hyperplasla!glandular stomach 2 ( 11) (
0 0) (
0 0 0) ( 0)
2 l 0 ( 13) ( 7) ( 0) (
0 0)
2 ( 9J
l 0 0 ( 5J ( 0) ( 0)
3 4 ( 11) ( 14)
0 ( 0) (
0 0)
liver ansi ectasis 0 OJ (
0 OJ (
0 0 0) ( OJ
0 l 0 ( 0) ( 7J ( 0) (
0 0)
l ( 5)
l 2 0 ( 5) ( 9J ( 0)
2 5 ( 7) ( !8J
5 ( 18) (
0 0)
mfarct 0 0) (
l 5J (
0 0 0) ( 0)
0 0 0 ( OJ ( 0) ( OJ (
0 OJ
0 ( 0)
0 0 0 ( 0) ( 0) ( 0)
1 0 ( 4) ( 0)
0 ( 0) (
0 0)
necros1s:central 0 0) (
0 OJ (
0 0 OJ ( 0)
0 0 0 ( 0) ( 0) ( 0) (
0 0)
0 ( 0)
1 0 0 ( 51 ( 0) ( OJ
0 l ( 0) ( 4)
l ( 4) (
0 0)
necrosis: foca l 0 0) (
l 5J (
l 0 5J ( 0)
l 0 2 ( 7J ( 0) ( 131 (
0 0)
2 ( 9)
3 3 0 ( 14) ( 14) ( 0)
3 4 ( 11) ( 14)
l ( 4J (
0 OJ
fatty change 0 OJ (
l 5J (
0 0 OJ ( 0)
0 l 0 ( OJ ( 7) ( OJ (
0 OJ
0 ( OJ
l 0 0 ( 5) ( OJ ( OJ
0 1 ( 0) ( 4J
0 ( OJ (
0 0)
dePOSit of amYlOid 0 OJ (
l 5) (
0 0 OJ ( OJ
0 0 1 ( OJ ( 0) ( 7J (
0 OJ
0 ( OJ
0 0 0 ( 0) ( OJ ( OJ
0 0 ( OJ ( OJ
0 ( OJ (
0 OJ
Significant difference : * ; p & 0.05 :n::p;;iiiQ,Ol Test of Chi Square m:Slisht :Moderate : Marl(ad :Seuere
(IIPT150) BAIS2
_.::;...
-
;).
STUDY NO. : 0!05 ANI HAL : HOUSE BOFI REPORT TYPE : AI SEX : HALE
1115TOLOGICAL FINDINGS ; NON-NEOPLASTIC LESIONS DEAD AND IIDRIBUNO AIIIHALS (0-IOSW)
(SUMMARY)
PAGE : 5
Organ__ Findings
Group Nama llo. of Ammals
(])
(%)
Control 19
(3) (%) (%)
(%)
(])
(%)
10 ppm 15
(2) (3) (%) (%)
(4)
(%) (])
(%)
50 ppm 22
(3) (%) (%)
(4)
(%) (])
(%)
250 ppm 28
(3)
(%) (%) (%)
[Digestive SYstem!
liver dePOSit of hemosiderin
deseneration:central
granulaticn
hYPerotasia
fH::rOSIS
clear cell focus
baSOPhi lie cell focus
vacuolic chansa:central
pancreas grarulation
crsa