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jt JiiU) K-6//7 Ofc) 104-WEEK DIETARY STUDY IN RATS 1-2-DIBROMO-3 CHLOROPROPANE (DBCP) SUPPLEMENTARY HISTOPATHOLOGY REPORT TO FINAL REPORT DATED OCTOBER 28, 1977 Submitted to Dow Chemical Company Midland, Michigan HAZLETON LABORATORIES AMERICA, INC. asco leesbubcj turnpike Vienna, Virginia aaieo usa June 26, 1978 r>0 131874 CONF I DFNTIA1 g>] HAZLETON ^5^ LABORATORIES AMERICA. INC. SPONSOR: Dow Chemical Company MATERIAL: l-2-Dibromo-3 Chloropropane (DBCP) SUBJECT: SUPPLEMENTARY HISTOPATHOLOGY REPORT TO FINAL REPORT DATED OCTOBER 28, 1977 104-Week Dietary Study In Rats Project No. 174-122 DATE: June ?6, 1978 INTRODUCTION The results of the following histopathology evaluations not previously included in the final report are presented in this supple mentary report: i 1. In accordance with Project Sheet No. 4 dated May 25, 1977, selected tissues were evaluated microscopically from twenty rats which had died or were sacrificed moribund during the study. A listing of the findings by individual animal is presented in Table 7B. 2. At termination of the study, the following tissues were evaluated from the control and high-dose rats which died or were sacrificed moribund during the study or were sacrificed at termination: brain, pituitary, thoracic spinal cord, eyes, thyroids, lung, heart, liver, esophagus, spleen, kidneys, adrenals, stomach, small Intestine, large Intestine, mesenteric lymph node, urinary bladder, pancreas, testes with epididymides, seminal vesicles and prostate, ovaries, uterus, skin, rib junction, bone marrow, nerve with muscle, tissue masses, and unusual lesions.8 Sections a The findings regarding the testes with epididymides, seminal vesicles, prostate, and urinary bladder of the males have been reported previously and are not included in this report. DO 1 B1 8 70 f.ONF T OF NT T At ^HAZLETON LABORATORIES AMERICA. INC 2- - of stomach, liver, and kidneys were also evaluated from the low- and mid-dose rats. The indivldaul findings are presented in Tables 7B (animals sacrificed Week 104) and 7C (deaths and moribund sacrifices). The incidence of neoplasia is presented in Table 8 and the incidence of chemically-induced non-neoplastic lesions in presented in Table 9. RESULTS 1. A variety of spontaneous neoplasms were observed including an embryonal nephroma in one control male, an endometrial stromal sarcoma in the uterus of one control female, and in an additional control female, multiple tissue involvement by malignant fibrous histiocytoma along with a mammary gland adenocarcinoma. A malignant fibrous histio cytoma was also observed in one low-dose male and mucinous adenocarcinoma of the small intestine was present in one low-dose female. A histiocytic lymphoma was present in one mid-dose male and hemangiosarcoma involving the pancreas and spleen was present in one additional mid-dose male. A renal tubule carcinoma was present in one mid-dose male and was histo logically comparable to those renal neoplasms observed in additional rats at termination of the study. Spontaneous neoplasms observed in one mid-dose female consisted of a fibroma of the ovary and a mammary gland fibroadenoma. In the high-dose treated rats from which tissues were evaluated (seven males and four females), hepatocellular carcinomas were observed CONFTDFNT TAl 1 HAZLETON r- LABORATORIES AMERICA. INC. 3- in three rats, with single cases of hemangiosarcoma, uterine adenocar cinoma, malignant mixed tumor of the kidney, and an embryonal neophroma. Mammary gland tumors were noted in two of the female rats with mammary adenocarcinoma and fibroadenoma in one rat and mammary fibroadenoma in the other rat* Chemically-induced neoplasms were observed in the kidneys and included renal tubule carcinomas in three of the high-dose male3 and a renal tubule adenoma in one high-dose female. In conclusion, microscopic evaluation of selected tissues from 20 of the animals which died or were sacrificed moribund during the study revealed chemically-induced neoplasia in the kidneys consisting of adenomas and carcinomas of renal tubule epithelial origin. These neoplasms were observed in four of the high-dose rats of either sex and one of the mid-dose males. A variety of other spontaneously occuring neoplasms were observed. 2. Histopathology evaluations at termination of the study revealed chemically-induced neoplasia in the kidney and stomach with a dose-related appearance. Stomach tumors were not present in the low-dose rats and kidney tumors were noted in only single low-dose male and female rats. The neoplasia observed consisted of squamous cell papillomas and carcinomas in the nonglandular region of the stomach and kidney tumors, both benign and malignant, which arose from the renal tubule epithelium. A slightly increased incidence of liver neoplasia was also apparent in the treated rats; however, the number of animals affected was much less than that observed with the gastric and renal neoplasms. Spontaneously occurring DO 131R ? 7 CONFTDFNTTAL HAZLETOrM LABORATORIES AMERICA. BMC -4- neoplasia was observed in a number of other tissues (tumor incidence, see Table 8). In addition to the chemically-induced neoplasms, a variety of other chemically-induced lesions were noted in the kidney, stomach, and, to a lesser extent, in the liver. In the kidney, focal renal tubule epithelial hyperplasia and megalocytic cells were apparent in the lining of the renal tubules. In the nonglandular region of the stomach, acanthosis and hyperkeratosis were present with a markedly increased incidence in the high-dose rats along with increased basal cell activity. In the liver sections, an increased incidence of peliosis hepatis was noted in the treated rats (see Table 9). Various spontaneous disease lesions and incidental findings were noted as presented for individual animals in the detailed histopathology incidence table. The more commonly noted lesions consisted of geriatric changes in the adrenal glands consisting of medullary cell hyperplasia and focal vacuolar degeneration of the cortex with sinusoid ectasia and occasional hematocysts. Heart sections revealed myocardial fibrosis and nonsuppurative myocarditis, primarily in the male rats. Chronic respiratory disease was noted in nearly all rats and consisted of peribronchial and perivascular lymphoid hyperplasia along with occasional small foci of pneumonitis. Also, occasional bronchlectatic abscesses were noted. Liver sections revealed a minimal to moderate degree of bile duct proliferation and nonsuppurative pericholangitis along with no 131B2S OONFTDFNTTA1 HAZLETON LABORATORIES AMERICA. INC r -5- occasional foci of altered hepatocytes composed primarily of vacuolated or basophilic cells. Occasional microgranulomas were noted. Kidney sections, in addition to revealing the chemically-induced neoplasms and other proliferative lesions as previously described, revealed rather severe chronic interstitial nephritis in the male rats which was essentially comparable in severity in the control and treated animals. In the female rats, less severe interstitial nephritis was present. However, a greater incidence of calculi in the renal pelvis with focal proliferation of the renal pelvic epithelium was noted in the females. Chemically-induced lesions were present in the nonglandular region of the stomach as previously described. Sections of the gastro intestinal tract were otherwise essentially normal with the exception of occasional nematode parasites in the large intestine and occasional instances of periarteritis. In the pancreas, focal nonsuppurative pancreatitis was noted in occasional rats and lobular atrophy was present with ductal cell proliferation. Occasional instances of periarteritis were also noted. A variety of other incidental and spon taneous disease lesions were noted in occasional animals, but were considered of insufficient frequency for discussion. In conclusion, dietary administration of DBCP at levels of 0.3, 1.0, and 3.0 mg/kg/day for 104 weeks resulted in a tumorigenic effect in the kidneys and nonglandular region of the stomach with the greatest incidence of neoplasia being observed in the high-dose rats HAZLETON LABORATORIES AMERICA. INC. r - 6- with lesser numbers of tumors at the mid-dose level and only rare lesions at the low-dose level. In addition, a marginal neoplastic response was observed in the livers of the treated rats. Other treatmentrelated lesions consisted of peliosis hepatis in the liver, renal tubule epithelial hyperplasia and megalocytosis in the kidneys, and acanthosis and hyperkeratosis with increased basal cell activity in the nonglandular region of the stomach. Spontaneous disease lesions and incidental findings were considered within normal limits for rats of this age and strain and were generally comparable between the control and high-dose treated groups. Submitted by VINCENT J./PICCIRILLO, Ph.D. Senior Staff Toxicologist Toxicology Department Pathology Director Pathology Department Report Preparation: Kundzins pah DO 131830 OONFTDFNTTAl -7- r KEY TO DETAILED HISTOPATHOLOGY INCIDENCE TABLE Type of Finding 0 - Tissue Absent X - Tissue Examined and Not Remarkable A - Autolysis P Finding Present Grading or Degree of Finding 1 = Minimal 2 = Slight 3 = Moderate 4 * Moderately Severe 5 = Severe 00 13183) OONFTDFIMl IAI Table 7B Individual lllstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION BRAIN Astrocytoma Indentation from Pituitary SPINAL CORD PITUITARY Adenoma Microcyst Focal Chromophobe Hyperplasia THYROID C-cell Carcinoma Diffuse C-cell Hyperplasia Focal C-cell Hyperplasia PARATHYROID Hyperplasia ADRENAL Pheochromocytoma Focal Medullary Cell Hyperplasia Focal Vacuolar Degeneration of Cortex Focal Cortical Cell Degeneration Pigment Sinusoid Ectasia ____________________________ Group 1_____________ 11111111111111111111 99999999999999999999 11111122222222222222 Animal 99999900000001111112 Number: 13467801 2 34790124890 XX xxxxxxxxxx X X X X XX p P X X X X X X X XXXXXXXO X X X X X XX pp X0XXXXX p p XX XX XX XXXXXX XX P p p pp p I 00 1 P P PP PPP P P PPP P PP P X DO 131B3? CONFTDFNTTAl Table 7B - Continued Individual Hlstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males .> ORGAN AND DESCRIPTION HEART Myocardial Fibrosis Arteritis Focal Nonsuppurative Myocarditis Focal Nonsuppurative Endocarditis LUNG Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Focal Pneumonitis Purulent Exudate SPLEEN Congestion Increased Extramedullary Hematopoiesis LIVER Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Micro granulomas Focal Hepatic Necrosis Tyzzer's Disease Pellosls Hepatis Sinusoid Ectasia DO 131 ROD CONFTDFNTTAl Group 1 1 1 11111 1111 1111 11111 9 9 9 9 9 99 9 9 9 9 9 9 9 9 9 99 9 9 1 1 11112 2 2 2 2 2 2 2 2 2 2 2 2 2 Animal 9 9 9 9 9 9 0 0 0 0 0 0 0 11 11112 Number: 1 3 4 6 7 8 0 12 3 4 7 9 0 1 2 4 8 9 0 222222 22332 P 22211 2 2 2 353333333 233332 23243 33 32 23 33 3233 2322 3333 PPP P P xxxxxxxxxxx X XX pPp p VO i 33 2222212 211 3 2321 222222 2212121112 2221 PP PPP PP PPP PP PP PP PP PPP PPP PP PPP PP PP PP PPPPP PP P P P Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Hales ORGAN AND DESCRIPTION Group 1 11111111111111111111 9999999999999999 9 9 9 9 11111122222222222222 An ima 19999 990000000111111 2 Number: 13467801234790124890 KIDNEY Chronic Interstitial Nephritis Extramedullary Hematopoiesis Cortical Cyst Congestion Focal Proliferation of Renal Pelvic Epithelium Calculi in Renal Pelvis Nonsuppurative Pyelitis STOMACH Periarteritis 4 5 3 2 5 33332424232132 P PP p PP pp P Pp P p XXXXX XXXXXXXXXXXX X p 0 1 SHALL INTESTINES X X X X X X XXXXXXXXXXX X X X LARGE INTESTINES Nematode Parasite X X 0 X X X XXXXXXXXX X p XX PANCREAS Islet Cell Adenoma Focal Nonsuppurative Pancreatitis Lobular Atrophy Ductal Cell Proliferation Periarteritis MESENTERIC LYMPH NODE Congestion NERVE MUSCLE DO 131834 confidfnttai XXXXX X XX 22 2 P P P pp p p XXXXXX X X p XX X X X p XXX p XXXXXXXXX XXX X XXX X X XX X X X X X X X X X XX X X X X X X X X X Table 7B -- Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males 3 ORGAN AND DESCRIPTION EYE STERNUM ESOPHAGUS TRACHEA Nonsuppurative Tracheitis SKIN RIB JUNCTION MAMMARY GLAND UNUSUAL LESIONS Fibroma Mammary Gland Adenocarcinoma Keratoacanthoma Neurofibroma Cutaneous Ulceration __________ ______________ Group 1 111111llllllli'l 11111 99999999999999999999 11111122222222222222 Animal 99999900000001111112 Number: 134678012347901248 9 0 XXXXXXXXXXXXXXXXXXXX xxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxoxxxxx XX XX XX p ppp p pppp ppp pp xxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxoxxxo X 1 r<1 ftOr f ONFTDFNTTA| Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION BRAIN Granular Cell Blastema SPINAL CORD PITUITARY Adenoma Microcyst Focal Chromophobe Hyperplasia THYROID C-Cell Adenoma Focal C-Cell Hyperplasia ADRENAL Pheochromocytoma Focal Medullary Cell Hyperplasia Focal Vacuolar Degeneration of Cortex HEART Myocardial Fibrosis Focal Nonsuppurative Myocarditis LUNG Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Focal Pneumonitis Aspirated Blood CnOoNFT0FNT1AI, Group 1 - Continued 1 1 1111 111I1 99999999999 22222222222 Animal 2 2 2 2 2 2 3 3 3 3 4 Number : 1 4 5 6 7 8 0 2 4 5 0 XXXX XXXXXX P XXXXXXXXX0X XXX X0 X P PP P P XXXX XX X X P PP XX X PP Pp p Pp PP X 32322 22333 1 33333332233 32 223232 223 P P - i Isa 1 Table 7B - Continued Individual llistopathology Findings Albino Rats Receiving l-2-Dibrotno-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION SPLEEN Congestion LIVER Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Infarction Focal Hepatic Necrosis Sinusoid Ectasia Hemorrhage Microgranulomas KIDNEY Chronic Interstitial Nephritis Cortical Cyst Congestion Focal Proliferation of Renal Pelvic Epithelium Calculi in Renal Pelvis STOMACH SMALL INTESTINE LARGE INTESTINE Nematode Parasite ] 318^7 OONFTDFN1 TA! Group 1 - Continued 11111111111 99999999999 22222222222 Animal 22222233334 Number: 1__ 4 567802450 XX xxxxxxxx p 222 2321 22222122211 PP PP PP PP PPP P PP P P PP 33443113325 P PP P PP P XXXXXX_X_ X_X__X X xxxxxxxxxxx xxxxx xxxxx Table 7B -- Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION PANCREAS Lobular Atrophy MESENTERIC LYMPH NODE NERVE MUSCLE EYE STERNUM ESOPHAGUS TRACHEA Nonsuppurative Tracheitis SKIN RIB JUNCTION UNUSUAL LESIONS Fibroma Myxosarcoma Squamous Cell Carcinoma Hemangiopericytoma Subcutaneous Abscess DO 131838 OONFTOFNTTAl Animal Number: Group 1 - Continued 11111111111 99999999999 22222222222 22222233334 14567802450 xxxxxxxxx X p xxxxxxxxxxx xxxxxxxxxox xxxxxxxxxox xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx X XX X x p p ppp p xxxxxxxxxxx xxoxxxxxxxx ^' Table 7B - Continued Individual Hlstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION LIVER Neoplastic Nodule Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Foci of Vacuolated Hepatocytes Congestion Foci of Altered Hepatocytes Microgranulomas Peliosis Hepatis KIDNEY Renal Tubule Carcinoma Chronic Interstitial Nephritis Cortical Cyst Congestion Nonsuppurative Pyelitis Focal Renal Thbule Cell Hyperplasia STOMACH Animal Number: Group 2 11111111111111111111 99999999999999999999 33333333333333333333 11111222222333333334 2347 802357 8014 5678 91 PP 32 32 P P P 22323333222222222 222323333222222222 PP PP PPP P P P PPP PP PP P P P PP P PPP P 34352433432231332212 p p P P PP PPP P P P xxxxxxxxxxxxxxxxxxxx Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION LIVER Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Foci of Vacuolated Hepatocytes Congestion Foci of Altered Hepatocytes Microgranulomas Focal Hepatic Necrosis Peilosls Hepatls Hemorrhage KIDNEY Chronic Interstitial Nephritis Cortical Cyst Congestion Focal Proliferation of Renal Pelvic Epithelium Focal Renal TXibule Cell Hyperplasia STOMACH Group 2 - Continued 111 11 1 1 1 11 1 99999999999 33333 333333 Animal 4 4 4 4 4 5 5 5 5 5 6 Number: 3 5 6 7 9 1 2 3 6 7 0 123 2 21 123 2 2121 P P PP P PP PP P PPPP P P PP P 52232521423 P PP P PP P P xxxxxxxxxxx O' l HO 131840 CONFTDFNT 7AI Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION _Group 3 11111111111111111111 99999999999999999999 44444444444444444444 Animal 33444444555555566667 Number: 4802578903456780157 1 LIVER Hepatocellular Carcinoma Neoplastic Nodule Malig. Lymphoma, Lymphocytic Type Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Microgranulomas Focal Hepatic Necrosis Peliosis Hepatis Hemorrhage P 2 2 2 231 2 2 12 13 2 2 1 11 222231 22221213 2 2 1 PP PPP P PP PP P P PPPP PPPPP P P PP P PP PP KIDNEY Renal Ttibule Adenoma Benign Mixed Tumor Malig. Lymphoma, Lymphocytic Type Arteritis Chronic Interstitial Nephritis Cortical Cyst Congestion Focal Proliferation of Renal Pelvic Epithelium Focal Renal Tubule Cell Hyperplasia Megalocytic Renal Tubule Epithelial Cells 4 242 P PP P P P 1 2122 PPPPP 2 4 32 2 4 PP PP P P PP P P 4 no CONP TDFNT r^| i i Table 7B -- Continued Individual Hlstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION STOMACH Squamous Cell Carcinoma Focal Ulceration in Glandular Mucosa Focal Ulceration in Nonglandular Region Acanthosis Hyp er kera tosis Submucosal Edema Pleocellular Inflammatory Infiltrate Focal Gastritis Basal Cell Activity Group 3 11111111111111111111 9999999 9' 999999999999 4444 44 44 444444444444 Animal 33444444555555566667 Number: 48025789034567801571 XX XXXXX XX pp p pp p pppp p p ppp p p p p pp p DO 131R4? CONFTDFNTTA1 Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION LIVER Hepatocellular Carcinoma Bile Duct Proliferation Nonsuppurative Pericholangitis Congestion Foci of Altered Hepatocytes Peliosls Hepatis Hemorrhage KIDNEY Chronic Interstitial Nephritis Cortical Cyst Megalocytic Renal Tubule Epithelial Cells STOMACH Acanthosis Hyperkeratosis Group 3 - Continued 111111 9 99 9 9 9 4 44 4 4 4 Animal 777778 Number: 245890 P 2 22 2 2 22 P PP PPPP P 32 P P XXXX 3 Of) 1 31843 CONFTDFNTTAl Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION BRAIN Astrocytoma Granular Cell Blastoma SPINAL CORD PITUITARY Adenoma Microcyst Focal Chromophobe Hyperplasia THYROID PARATHYROID Hyperplasia ADRENAL Pheochromocytoma Focal Medullary Cell Hyperplasia Focal Vacuolar Degeneration of Cortex Focal Cortical Cell Degeneration Pigment Sinusoid Ectasia Atrophy HEART Myocardial Fibrosis Focal Nonsuppurative Myocarditis 00 101844 nONFTDFNT TAI _Group 4 111111111111111111 999999999999999999 555555555555555555 Animal 555555667778889999 Number: 123569181593591 3 5 7 XXXXXX X p XXXXXXXXX XXXXXXXXXXXXXXXXXX XXXX X X XX XX X p ppp p pp pp XXXXXXXXXXXXXXXXXX too pp p pp p ppp p p pppp pp pp p p ppppppppppp p ppp p ppp XX 2 22332532323222 3 11 Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION LUNG Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Focal Pneumonitis Bronchiectatic Abscess Formation SPLEEN Congestion Increased Extramedullary Hematopoiesis Developmental Abnormality LIVER Hepatocellular Carcinoma Neoplastic Nodule Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Microgranulomas Focal Hepatic Necrosis Peliosls Hepatls Sinusoid Ectasia Hemorrhage DO 131845 CONFTDFNTTAI Group 4____________________________________________ 111111111111111111 999999999999999999 555555555555555555 Animal 555555667778889999 Number: 1 2 3 5 6 9 1 81593591357 443353455333 343 333 3 3 3 2 3 3 3 3 2 3 2 3 3 3 3 2 13 PP PP P XXX X X XXX X XX XX PP PP P P PP P PP 2 22 3222222 2 12 2 2 2 2 22 2 2 2 2 2 2 2 2 222 222 PP PP PPP P P P PP PP P P P PP P P P P PP P P P PP P PP PP PPP P PPPP P P PP P PP Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION KIDNEY Renal Tubule Adenoma Renal Tubule Carcinoma Chronic Interstitial Nephritis Cortical Cyst Focal Proliferation of Renal Pelvic Epithelium Focal Renal Tubule Cell Hyperplasia Megalocytlc Renal Tubule Epithelial Cells STOMACH Squamous Cell Papilloma Squamous Cell Carcinoma Focal Ulceration in Nonglandular Region Acanthosis Hyperkeratosis Focal Gastritis Basal Cell Activity Inclusion Cyst SMALL INTESTINE Periarteritis LARGE INTESTINE Nematode Parasite ____________________ Group 4 111111111111111111 999999999999999999 555555555555555555 Animal 555555667778889999 Number: 1 2 3 5 6 9 181593591 3 5 7 P PP P P P PP PP 332445332435453444 P PPPP PP P PPP PP P PPP P PPP PPPPPPPPPPPPPPPPPP P PPPPPP P PPPP PPP PP PPPPPPPPPPPPPPPPPP PPPPPPPPPPPPPPPPPP P pppp P PP PP PPP P xxxxx xxxxxxxxxxxx p xxxxx xxxxxxxxoxxx p oo 1 31 R4f-, CONFTDFNT TA1 Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION PANCREAS Acinar Cell Adenoma Focal Nonsuppurative Pancreatitis Lobular Atrophy Periarteritis MESENTERIC LYMPH NODE Congestion Sinus Histiocytosis Periarteritis NERVE MUSCLE EYE Keratitis STERNUM ESOPHAGUS Acanthosis Hyperkeratosis TRACHEA Nonsuppurative Tracheitis SKIN DO 131047 CONFTDFNTTAl Group 4 111111111111111111 999999999999999999 555555555555555555 Animal 555555667778889999 Number: 1 23569181593591357 XXX X X XXX XX X X p pp pp p pp X X X X X XXX XX XXX p ppp p p X X X XX X X X X X X X X X X X X X X X X XX X X X X X X X X X X X X X XXX XX X X X X X X X X X X X X p X X X XX X X X X X X X X X X X X X XXX XX p p XXXXXXX XX X X p p p XXXXXXXXXXXXXXXXOX Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Males ORGAN AND DESCRIPTION RIB JUNCTION SALIVARY GLAND Hemangiosarcoma UNUSUAL LESIONS Keratoacanthoma Squamous Cell Carcinoma Fibrosarcoma Hemangiosarcoma Circumscribed Fat Necrosis Group 4 111111111111111111 999999999999999999 555555555555555555 Animal 555555667778889999 Number: 123569181593591357 XXXXXXXXXXXXXXXXXX P P P P P P 00 1 31 R4fi conftdfntTA| Albino Rats Table 7B - Continued Individual Histopathology Findings Receiving 1-2-Dibromo--3 Chloropropane (DBCP) Animals Sacrificed Week 104 Females for 104 Weeks ORGAN AND DESCRIPTION BRAIN Indentation from Pituitary SPINAL CORD PITUITARY Adenoma Focal Chromophobe Hyperplasia Angiectasia Hicrocyst THYROID C-cell Carcinoma Follicular Cell Adenoma Follicular Cell Carcinoma PARATHYROID Hyperplasia ADRENAL Pheochromocytoma Cortical Adenoma Focal Medullary Cell Hyperplasia Focal Vacuolar Degeneration of Cortex Sinusoid Ectasia Hematocyst Do 1 3 1 84 9 ^D Ffyp Group 1 11111111111111111111 99999999999999999999 22222222222222222222 Animal 55555556666667777888 Number: 124568934 6__ 7 891357014 XXXXXXX X XXXXXXXXX X PP XXXXXXXXX xxxxxxxxxxx X XX PPPP P P % P PPPP pp PP Pp p PP p XXXXXXXXX XXXXXXX X p p p 0 P P PP P P P P__P P P P P P P - -- PPPPPPPPPPPPP P P PP P P P P PP P P P P Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dlbromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ) ORCAN AND DESCRIPTION HEART Myocardial Fibrosis Focal Nonsuppurative Myocarditis LUNG Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Congestion Focal Pneumonitis Aspirated Blood SPLEEN Congestion Increased Extramedullary Hematopoiesis LIVER Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Diffuse Vacuolation of Hepatocytes Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Microgranulomas Cholangiectasis no 131880 OONFTDFNTTAl _Group 1 11111111111111111111 99999999999999999999 22222222222222222222 Animal 55555556666667777888 Number: 12456893467891357014 XXX X X XXXXX XXX 2 2 22 22 2 3 3 3 3 3 3 4 3 3 2 3 2 33333333 2 3 3 2 3 3 3 3 3 3 2 2 33232323 P P PP r KOJ' I XXXXXXXXXXX XXXXX p Pp p XX 2 12 2 2 2 11 31 2 3 2 12 2 22 1 1 2112 2 2 3 PP P PP P PP P PP P PP PPP PP P PP P PP P P P Table 7B - Continued Individual Histopathology Findings Albino RatB Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ) ORGAN AMD DESCRIPTION KIDNEY Focal Mineralization Chronic Interstitial Nephritis Cortical Cyst Congestion Focal Proliferation of Renal Pelvic Epithelium Calculi In Renal Pelvis STOMACH SMALL INTESTINE Mucinous Cystadenocarclnoma LARGE INTESTINE Nematode Parasite PANCREAS Focal Nonsuppurative Pancreatitis Lobular Atrophy Periarteritis MESENTERIC LYMPH NODE Congestion NERVE MUSCLE EYE DO 1.31BM f.ONF IDF NTT Al Group 1 11111111111111111111 99999999999999999999 22222222222222222222 Animal 55555556666667777888 Number: 1245689346789 1__ 3 5 7 0 1 4 X 3 1112 1 2 1 11 PP P P PPP P P PPP PP PP P PPP PP PP PP xxxxxxxxxxxxxxxxxxxx to xxxxxxxxxxxxxxx xxxx p xxxxxxxxxxxxx xxxxxx p XXXXXXXX XXXXXXXXX 2 PP P XXXXXXXXXXXX xxxxxxx P oxxxxxxxxxxxxxxxxxxx oxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxx 1 Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-DIbromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION STERNUM ESOPHAGUS TRACHEA Nonsuppurative Tracheitis SKIN Dermatitis Folliculitis RIB JUNCTION MAMMARY GLAND Galactoceles Active UTERUS Endometritis Focal Cystic Endometrial Hyperplasia Endometrial Stromal Polyp OVARY Paraovarian Cyst Cyst Purulent Salpingitis DO 13185?' CONF TOFNT TAl Group 1 11111111111111111111 99999999999999999999 22222222222222222222 Animal 55555556666667777888 Number: 1 2 4 5 6 893467891357014 XXXXXXXXXXXXX XXXX X O X XXXXXXXXXXXXXXXXX XXX pp XX X X X X XX 2 p X X X XX X X X X X X X X X X X X X XX X X 0 XX X X X X O X XX pp p pp p X XX XXX XX p pppp pp pp pp p pp X X XXXXX X p p XXXXX XXXX p p I 00 1 Table 7B -- Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION UNUSUAL LESIONS Mammary Fibroadenoma Mammary Gland Adenocarcinoma Endometrial Stromal Sarcoma Chronic Active Mastitis URINARY BLADDER Group 1 11111111111111111111 99999999999999999999 22222222222222222222 Animal 55555556666667777888 Number: 12456893467891357014 P PP P P P PP PP P xxxxxxxxxxxxxxxxxxxx 1 N) vo i 00 131853 CONFTDFNTTAl- Table 7B - Continued Individual llistopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION BRAIN Astrocytoma Internal Hydrocephalus Indentation from Pituitary SPINAL CORD PITUITARY Adenoma Microcyst Focal Chromophobe Hyperplasia THYROID ADRENAL Pheochromocytoma Focal Medullary Cell Hyperplasia Focal Vacuolar Degeneration of Cortex Foci of Extramedullary Hematopoiesis Sinusoid Ectasia HEART Myocardial Fibrosis Focal Nonsuppurative Myocarditis _______ Group 1 - Continued . 11111111111 99999999999 22222222223 Animal 88899999990 Number: 56801235680 XXXXX XX p p XX p XXXXXXXXXXX XX pp p pp pp p p XXXXXXXXXXX X p p pp p pppppppp p pp ppp pppp XXXXX X 2 12 1 2 DO 131354 CONFTDFNTTAl Table 7B - Continued Individual Ifistopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION LUNG Peribronchial Lymphoid Hyperplasia Perivascular Lympoid Hyperplasia Aspirated Blood SPLEEN Increased Extramedullary Hematopoiesis LIVER Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Microgranulomas Focal Hepatic Necrosis Tyzzer's Disease Hemorrhage KIDNEY Chronic Interstitial Nephritis Cortical Cyst Focal Proliferation of Renal Pelvic Epithelium Calculi in Renal Pelvis Focal Renal Tubule Cell Hyperplasia 00 131805 OONFTOFNTTAI Group 1 - Continued 11111111111 99999999999 22222222223 Animal 88899999990 Number: 5 6 8 0 1 2 3 5__ 6 8 0 32223233222 2 223233222 PP X XX XX X X P P PP 23 21 21 2 221 21 222 PP P P PP P PP P P PP PP PP PP P P _ ---- pX 1113 13 ppp ppp P PPPPPP PPPPPP Table 7B - Continued Individual Hlstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Cbloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAH AND DESCRIPTION STOMACH Periarteritis SMALL INTESTINE LARGE INTESTINE PANCREAS Periarteritis MESENTERIC LYMPH NODE NERVE MUSCLE EYE Harderlan Gland AdenitlB STERNUM ESOPHAGUS TRACHEA Nonsuppurative TracheltlB SKIN 00 131856 CONFIDENTIAL Group 1 - Continued 11111111111 99999999999 22222222223 Animal 88899999990 Number: 56801235680 XX xxxxxxxx p xxxxxxxxxxx xxxxxxxxxx p XX xxxxxxxx p xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx XX xxxxxxxx p xxxxxxxxxxx xxxxxxxxxxx p pppp xxxxxxxxxxx Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibrotno-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION RIB JUNCTION MAMMARY GLAND Calactoceles Active UTERUS Endometritis Focal Cystic Endometrial Hyperplasia Endometrial Stromal Polyp OVARY Cyst THYMUS UNUSUAL LESIONS Mammary Fibroadenoma Mammary Gland Adenocarcinoma Enlarged Subcutaneous Lymph Nodes URINARY BLADDER Group 1 - Continued 11111111111 99999999999 22222222223 Animal 88899999990 Number: 5 6 8 0 1 2 3 5 6 8 0 xxxxxxxx XXX X 0X000 P PP X XX P XXX XX X X X X X PP P PPP P P XXXXXXXXXXX no 131857 CONF TDFNTTAL l uu>> l Table 7B - Continued Individual Hlstopathology Findings Albino Rats Receiving 1--2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION Animal Number: Group 2 11111111111111111111111 99999999999999999999999 33333333333333334444444 77777888889999990001111 13469025690124565791237 LIVER Hepatocellular Carcinoma Neoplastic Nodule Cystic Cholangloma Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Microgranulomas Cholangiectasls Infarction Focal Hepatic Necrosis Peliosls Hepatls Sinusoid Ectasia Hemorrhage i31asa CONFTDFNTTAl KIDNEY Renal Tubule Carcinoma Focal Mineralization Chronic Interstitial Nephritis Cortical Cyst Congestion Focal Proliferation of Renal Pelvic Epithelium Calculi in Renal Pelvis Nonsup atlve Pyelitis Megalocytlc Renal Tubule Epithelial Cells P PP P 2 2 2 11 222 2 2 22 22 1 2 11 22 22 P PP PP P PP PPPPP P P PP P P PP P P P P P P X 22 12 P P P P P 22 U) P * P 42 P P 2311 P P 1 P P 11 PPPPPP P PP P PP P P P PPPPPP P PPPP PPPP P P PP P PP P PP PP PP PP Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION STOMACH Acanthosis Hyperkeratosis Submucosal Edema Animal Number: Group 2 11111111111111111111111 99999999999999999999999 33333333333333334444444 77777888889999990001111 13469025690124565791237 xxxxxxxxxxx xxxxxxxxxxx p p p CJ In I 131 SFj9 <-.ONF TrjFNT TA1 Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION Group 3 1111111111111111111 9999999999999999999 4444445555555555555 Animal 9999990000001112222 Number: 13467814 6 7893460235 LIVER Hepatocellular Carcinoma Neoplastic Nodule Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Microgranulomas Cholangiectasis P P 2 3 2 2 2 21233212 2 3 12 2 2 212332 21 PP P PP PP P PPP P PP PP PP PP P P PP PP P PP PP P P PP PP P KIDNEY Benign Mixed Tumor Dilation of Renal Pelvis Chronic Interstitial Nephritis Cortical Cyst Congestion Focal Proliferation of Renal Pelvic Epithelium Calculi in Renal Pelvis Focal Renal Tubule Cell Hyperplasia Megalocytlc Renal Tubule Epithelial Cells STOMACH Acanthosis Hyperkeratosis Basal Cell Activity DO 1 DIBAO CONFIDFNTTAI P P 125 1112 21 112221 1 PP P PPP PP P PP P P PPPPP P PPP PPP PPPP PPPPP P PP P PPP PP P PP xxxxxxxxxxxxx PPP PPP p p ______ : i uO>' l Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION LIVER Neoplastic Nodule Malignant Lymphoma, Lymphocytic Type Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Microgranulomas Cholangiectasis Peliosis Hepatis KIDNEY Malignant Lymphoma, Lymphocytic Type Chronic Interstitial Nephritis Congestion Focal Proliferation of Renal Pelvic Epithelium Calculi in Renal Pelvis Nonsuppurative Pyelitis Megalocytlc Renal Tubule Epithelial STOMACH Malignant Lymphoma, Lymphocytic Type Acanthosis Hyperkeratosis SMA". INTESTINE l .al Ulceration DO 131881 CONFTDFNTTAl Group 3 - Continued 11111111111 99999999999 55555555555 Animal 22233333333 Number: 68901234579 P P 23 22132 3 1 2 2 2 22 1 2 2 P P PP PP P P PP P PP P P P PPP P P P PP P 2 2 12 PP P PP P PP P 1 112 P PPP PPP PPP P PP p pp pp X p p X IX X--X-- X X p Albino Rats Table 7B - Continued Individual Hiatopathology Findings Receiving l-2-Dlbromo-3 Chloropropane (DBCP) Animals Sacrificed Week 104 Females for 104 Weeks ORGAN AND DESCRIPTION LUNG Hamartoma Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Congestion Focal Pneumonitis Aspirated Blood SPLEEN Congestion Increased Extramedullary Hematopoiesis LIVER Neoplastic Nodule Bile Duct Proliferation Nonsuppurative Pericholangitis Foci of Basophilic Hepatocytes Foci of Vacuolated Hepatocytes Focal Extramedullary Hematopoiesis Congestion Foci of Altered Hepatocytes Microgranulomas Cholangiectasis _____________________ Group 4 _______________________ 111111111111111111! 9999999999999999999 6666666666666666666 Animal 1111222233333334445 Number :1247123812356783495 2 33 2 23 22 2 2 22 2 2 P 3 2 33 2 2 32 P 22 3 3 22 2 2 P PP P 4 4 22 22 XX P X XX P X XX XX X PP XX PP 0 P 11 13 321 2 1 111 2 2221 221 22 PP PP P PP P PP PP P P PP PPP PP P P PP PP PP P PP DO 1 31 B63 OONFTDFNTTAl Table 7B - Continued Individual Hlstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females ORGAN AND DESCRIPTION Group 4 1111111111111111111 9999999999999999999 6666666666666666666 Animal 1111222233333334445 Number: 1247123812 356783495 KIDNEY Renal Tubule Adenoma Renal Tubule Carcinoma Focal Mineralization Chronic Interstitial Nephritis Focal Proliferation of Renal Pelvic Epithelium Calculi in Renal Pelvis Focal Renal Tubule Cell Hyperplasia Megalocytic Renal Tubule Epithelial Cells Congestion P P PPPP P P 212 11 11111122312 PP PPPP P PPPPP P PP PPPP P PPP P P PP P PPPP PPPPPPPPPPPPPPPPPPP PP STOMACH Squamous Cell Carcinoma Focal Ulceration in Nonglandular Region Pseudoeplthellomatous Hyperplasia Acanthosis Hyperkeratosis Basal Cell Activity PP PP P XXX P P PP P PP P PPP P PP P PPPPPPPPP PPP PPP P PP PPPP 0 SMALL INTESTINE xxxxxxxxxxxxxxxxxxx LARGE INTESTINE Nematode Parasite xxxxxxxxxxxxxx xxxx p PANCREAS Lobular Atrophy XX xxxxxxxxxxxxxxxx p MESENTERIC LYMPH NODE NERV 131864 OFNIIAI xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx V <V "0 Albino Rats Table 7B - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Animals Sacrificed Week 104 Females for 104 Weeks ORGAN AND DESCRIPTION MUSCLE EYE STERNUM ESOPHAGUS Group 4 1111111111111111111 99999999999999999 9 9 6666666666666666666 Animal 1111222233333334445 Number: 12471238123 56783495 xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxoxxx TRACHEA Nonsuppurative Tracheitis SKIN RIB JUNCTION MAMMARY GLAND Galactoceles Active UTERUS Endometritis Focal Cystic Endometrial Hyperplasia Endometrial Stromal Polyp OVARY Cyst Purulent Salpingitis Fibroma DO 131 ROD CONFTDFNTTAi PP PP P pp xxxxxxxxxx xxxxxoxxx xxxxxxxxxx oxxxxxxxx X p p pp X p 0X0X0 0 ppp ppp 0 p 00 XX x p pp p p pp p pp pp pp X pp ppp p X p pp p XXXXXX X X X XX pp p p p Table 7B - Continued Individual Histopathology Findings Albino Rats Receiving 1-2-Dibromo--3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 Females 3 ORGAN AMD DESCRIPTION UNUSUAL LESIONS Mammary Fibroadenoma Mammary Gland Adenocarcinoma Fibrosarcoma URINARY BLADDER ________________________________ Group 4 ______ 1111111111111111111 9999999999999999999 6666666666666666666 Animal 1111222233333334445 Number: 124712381235678349 5 PPPP PP PPP P P PPPPP PPP P xxxxxxxxxxxxxxxxxxx to DO 111800 CONFIDFNTTAl Table 7C Individual Hlstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males ORGAN AND DESCRIPTION BRAIN Astrocytoma Indentation from Pituitary SPINAL CORD PITUITARY Adenoma Carcinoma Focal Chromophobe hyperplasia THYROID Congestion ADRENAL Pheochromocytoma Medullary Cell Hyperplasia Vacuolar Degeneration of Cortex Sinusoid Ectasia HEART Myocardial Fibrosis Atrial Thrombosis Foci of Mineralization Endocardial Fibrosis Group 1 111111111111111111 999999999999999999 112222222222222222 Animal 990001111222333333 Number: 29568356723913 6 7 8 9 XXXXX OX P X X X XX P PP P P X X X X X X OXXX XXXXX XXX XX X 00X P X XX PP P PP XXX X 0 0XXXXX 0XXXX X P P PP PP 0 0 X XX X X pp P pp pp p pp 32 23 P 22 XXX 332 2 PP DO 1010O7 r.ONF TDFNT I At Table 7C - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Males for 104 Weeks ) ORGAN AND DESCRIPTION Group 1 111111111111111111 999999999999999999 112222222222222222 Animal 990001111222333333 Number: 2 9 3 6 8 3 5 6 7 2 3 9 1 3 6 7 8 9 LUNG Malignant Lymphoma, Lymphocytic Type Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Suppurative Necrotizing Pneumonia Congestion Bronchiectatlc Abscess Formation Pulmonary Edema Thrombosis (Pulmonary Artery) Aspirated Blood 0 P 32 4 32 2 23 355 135 32 2 22 3 3 22 32 P PP PPPP P P PPP PP P P P P SPLEEN Malignant Lymphoma, Lymphocytic Type Malignant Mixed Tumor, Metastatic Extramedullary Hematopoiesis Contracted XXXX0 XXXXX P p STOMACH Malignant Lymphoma, Lymphocytic Type Acanthosis Hyperkeratosis Focal Ulceration Gastritis Metastatic Calcification of Gastric Mucosa Hemorrhage Basal Cell Activity X X0X0 XX XXX p P pp p P pp p P pp Pp p p p p Do 13l86.fi C-ONF T DFN T T Al I c* i Table 7C - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males ORGAN AND DESCRIPTION MESENTERIC LYMPH NODES Malignant Lymphoma, Lymphocytic Type NERVE MUSCLE EYE BONE MARROW SKIN ESOPHAGUS RIB JUNCTION UNUSUAL LESIONS Hemangiosarcoma Mammary Gland Fibroadenoma Mammary Gland Adenocarcinoma Fibroma THYMUS Malignant Lymphoma, Lymphocytic Type MESENTERY PeriarteritiB 131869 CONF IDFNT I Al Group 1 111111111111111111 999999999999999999 112222222222222222 Animal 990001111222333333 Number: 295683567239 1 3 6 7 8 9 X X X X 0X 0 X X X X XX 0 X X X X XX 0 X X X X XX 0 X X X X XX 0 X X X X XX 0 X X X X XX 0 X X X X X0 0 X X XX X 0 0 X X X P XXX X X X X X X 0 X XXX X X X X X X X X XXX X X X X X X X o xXX X X X X X X X X XX X X X X X X X X X XXX X X X X X X X X XXX X X X X X X X X P p P PP I Ul I Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving 1-2-Dibromo--3 Cliloropropane (DBCP) Deaths and Moribund Sacrifices Males for 104 Weeks ORGAN AND DESCRIPTION Group 1 111111111111111111 999999999999999999 112222222222222222 Animal 990001111222333333 Number: 295683567239136789 LIVER Malignant Lymphoma, Lymphocytic Type Nonsuppurative Pericholangitis Bile Duct Proliferation Microgranulomas Congestion Vacuolated Hepatocytes Hepatic Necrosis Foci of Altered Cells Fatty Metamorphosis Extramedullary Hematopoiesis 0X P 22 222 22 22 2 1 32 223 P PPP P P PPP P PPP PPP PP P P P PP PP PP P KIDNEY Malignant Lymphoma, Lymphocytic Type Malignant Mixed Tumor, Primary Pyelitis Chronic Interstitial Nephritis Cortical Cyst Proliferation of Renal Pelvic Epithelium Ectopic Adrenal Tissue Congestion 0 XX P p P 45435 3 52 321 42 2 PP P PP P P PP P SMALL INTESTINE X X XX 0 X 0X0XXXX 0XXXX LARGE INTESTINE Dn ] 870 CONFTDFNTTAl PANCREAS Malignant Lymphoma, Lymphocytic Type Periarteritis XXX X 0 X 0 X X XXX X 0 X XXX XXX X 0 X 0 X X X XXX XXX p p Oi Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Males for 104 Weeks ORGAN AND DESCRIPTION TRACHEA Nonsuppurative Tracheitis Suppurative Tracheitis PARATHYROID Hyperplasia Group 1 111111111111111111 999999999999999999 112222222222222222 Animal 990001111222333333 Number: 2 95683567239136789 X PP P XX PP PP PP 00 13 ^ONFTOFNTTAl Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Males for 104 Weeks ORGAN AMD DESCRIPTION ___________________________ Group 2________________ 111111111111111111 999999999999999999 333333333333333333 Animal 111122223344455555 Number: 15691469230480 4 5 8 9 LIVER Neoplastic Nodule Hepatocellular Carcinoma Malignant Lymphoma, Histiocytic Type Malignant Lymphoma, Lymphocytic Type Nonsuppurative Pericholangitis Bile Duct Proliferation Congestion Basophilic Hepatocytes Vacuolated Hepatocytes Foci of Altered Cells Fatty Metamorphosis Extramedullary Hematopoiesis Hepatic Abscess Pellosis Hepatls Hepatocytic Degeneration Leukocytosis 00 0 P p p P 2 222 3 23 2 2 2 2 2 2 23 2 2 3 PP PPPP P PP PPP P PPP P PP P P PP P P P PP P KIDNEY Malignant Lymphoma, Lymphocytic Type Malignant Lymphoma, Histiocytic Type Malignant Mixed Tumor, Primary Chronic Interstitial Nephritis Cortical Cyst Proliferation of Renal Pelvic Epithelium Congestion Pyelonephritis Calculi in Renal Pelvis Metastatic Calcification JJ CONFTDFNTTA! 112 5 2 2 5 PP PP PPPPP P PP P P 00 332 P P PPP Table 7C - Continued Individual lllstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males ORGAN AND DESCRIPTION Group 2 111111111111111111 9 9999999999999999 9 333333333333333333 Animal 1 1 1 1 2 2 2 2 3 3 4 4 4 5 5 5 5 5 Number: 1 5 6 9 1 4 6 9 2 3 0 4 8 0 4 5 8 9 STOMACH Acanthosis Hyperkeratosis Focal Ulceration Gastritis Metastatic Calcification of Gastric Mucosa Hemorrhage Basal Cell Activity Submucosal Edema Congestion XXXX P PP P PP X 00 X0 PP PP P PP P P PP P P no 1 81 873 OONFTDFN7 TAI Table 7C - Continued Individual HIstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males ORGAN AND DESCRIPTION Group 3 111111111111111111111 999999999999999999999 444444444444444444444 Animal 333333444455566667777 Number: 12357913461 2 9 2 3 4 8 0 3 6 7 LIVER Neoplastic Nodule Malignant Lymphoma, Histiocytic Type Nonsuppurative Pericholangitis Bile Duct Proliferation Congestion Basophilic Hepatocytes Vacuolated Hepatocytes Hepatic Necrosis Foci of Altered Cells Extramedullary Hematopoiesis Peliosls Hepatis Hepatocytlc Degeneration Cholangiectasls 0 P P 2 3 22 2 2 22 3 2 22 2 2 32 2 2 32 22 2 P PP P P P PP PPPP P 2 2 PP 22 22 PP P PP PP P PPP P PP P P P PP P P PP KIDNEY Renal Tubule Carcinomas, Unilateral Renal Tubule Carcinomas, Bilateral Pyelitis Chronic Interstitial Nephritis Cortical Cyst Proliferation of Renal Pelvic Epithelium Congestion Calculi in Renal Pelvis Renal Tubule Epithelial Hyperplasia Megalocytic Cells (Renal Tubules) Necrosis of Renal Papilla 0 PP P P 3 2 32 322 223 235 3 3 445 PP P PP PP P PP PP PPPPPP P PP P P PP P P PP P n l-'SJft? 4 CONFTDFNTTA1 Table 7C - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males ORGAN AND DESCRIPTION Group 3 111111111111111111111 999999999999999999999 444444444444444444444 Animal 3333334444555666677 77 Number: 1235791346129234803 6 7 STOMACH Squamous Cell Carcinoma AcanthoBis Hyperkeratosis Focal Ulceration Gastritis Metastatic Calcification of Gastric Mucosa Periarteritis Hemorrhage Basal Cell Activity Submucosal Edema Congestion X XXXXXXX XXX XO P PP P PPP PP P PPP PP PP P PP P P P PP P l tn I DO 131875 CONFTOFNTTAl Table 7C - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males ) ORGAN AMD DESCRIPTION RAIN Indentation from Pituitary PINAL CORD ITUITARY Adenoma Focal Chromophobe Hyperplasia HYROID C-Cell Hyperplasia Group 4 1111111111111111111111111 9999999999999999999999999 5555555555555555555555555 Animal 5666667777778888888999955 Number: 8023470234670124678248 9 7 4 XOOXXX XXX xxxxxoxxxxxxx p pp xxoxxxxxxxxxoxxxxoxxxxxxx XOOXXX pp ppp ooooxx xxxx xoo xxxxoxxxxxxxooxxxoxxx p DRENAL Pheochromocytoma Medullary Cell Hyperplasia Vacuolar Degeneration of Cortex Sinusoid Ectasia Congestion X0X X XX p p p pp pp pppp pp pppp pp XX PPPP pp BART Thymic Carcinoma Myocardial Fibrosis Atrial Thrombosis Foci of Mineralization Septic Thrombus Suppurative Necrotizing Myocarditis Periarteritis (Coronary Arteries) 0 p 22 332 P P X 2 222 P P P xxxoxxx 2 3 2 32 P P 13187ft CONFrOFNlTAL UK)! Tabic 7C - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males ORGAN AND DESCRIPTION Group 4 1111111111111111111111111 9999999999999999999999999 5555555555555555555555555 Animal 5666667777778888888999955 Number: 8 0 2 347023467 0 1 2 4__ 6 78248974 UNG Metastatic Squamous Cell Carcinoma Metastatic Hepatocellular Carcinoma Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Suppurative Necrotizing Pneumonia Congestion Bronchiectatic Abscess Formation Hemorrhagic Necrotizing Pneumonitis Focal Pneumonitis Hemosiderin-Laden Macrophages 0X 3 3 P PP P 3 3 2 3 23 2 22 3 PPPPP P P 333333 PPPPPP P P 333 PPPP P P 33 PP PLEEN Extramedullary Hematopoiesis ITOMACH Squamous Cell Carcinoma Acanthosis Hyperkeratosis Focal Ulceration Metastatic Calcification of Gastric Mucosa Hemorrhage XXOXXXXXXXXXXXOXOO XXXX pp 0 P P P P PPPP PPPP X X XXX0 00 P PP p PP p Pp XX p pp ppp p p pp p p pp p I Uu>l l Of) r-ONp 1 -3 I B77 rDF^TM, Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-DIbromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Males for 104 Weeks ORGAN AND DESCRIPTION Group 4________________________________________________________ _ 1111111111111111111111111 9999999999999999999999999 5555555555555555555555555 Animal 5666667777778888888999955 Number: 8023470234670 1 2 4 6 7 8 2 4 8 9 7 4 IVER Neoplastic Nodule Hepatocellular Carcinoma Nonsuppurative Pericholangitis Bile Duct Proliferation Microgranulomas Congestion Basophilic Hepatocytes Vacuolated Hepatocytes Hepatic NecrosiB Foci of Altered Cells Extramedullary Hematopoiesis Pellosis Hepatis Metastatic Squamous Cell Carcinoma Periportal Fibrosis 0 P 22 22 3 22 2 3 22 2 2 2 PP PPPP PP PP PP P P P 0 00 P 32 32 P PPP PP 2 2 P 2 2 PP X 2 2 P PP PP P PP P PP PP 32 32 PP P PP P i Cn I C O N F ID E N T IA L IDNEY Renal Tubule Adenoma Renal Tubule Carcinomas, Unilateral Renal Tubule Carcinomas, Bilateral Malignant Mixed Tumor, Primary Periarteritis (Arcuate Arteries) Pyelitis Chronic Interstitial Nephritis Cortical Cyst Proliferation of Renal Pelvic Epithelium Congestion Pyelonephritis Metastatic Calcification Renal Tubule Epithelial Hyperplasia 4 n Pnl 1 fDAn A 1 TnKlll OO^ 0 P 0 P 00 X PP p P pp P 43 P 24 221 525 22 3 P 5 p 5334 PP 22 PP PP P PPP P PPP P P PP P p P Ppp PPP P PP P P P PPP P P P P Table 7C -- Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males ORGAN AND DESCRIPTION MALL INTESTINE ARGE INTESTINE Nematodiasis ANCREAS Periarteritis Lobular Atrophy Pancreatitis ESENTERIC LYMPH NODES Congestion ERVE USCLE Myositis YE Panophthalmitis Cataract Formation ONE MARROW AMMARY GLAND Active KIN DO i 3 1 CONFTDFNT rAl Group 4 1111111111111111111111111 9999999999999999999999999 5555555555555555555555555 Animal 5666667777778888888999955 Number: 8023470234670124678248 9 7 4 XXOXXOXXXXXXXXOXOOXXXXXXX XXOXXXXXOXXXXXOXOOXO XXXX P XXOXXXXX XXXXX0X00 X pP pp p XXX XXO XXXXXXXXXXOXOOXXXXXXO p XXOXXXXXOXXXXXXXXOXXXXXXX XXOXXXXXX XXXXXXXOXXXXXXX p X 0 0 X X X XXXXXXX XX ooxxxxxxx p p X X 0 X X X X X TX X X X X X X X 0 X X X X X X X 0 P xxoxxxxxxxxxx X X X 0 0 XXXXXXX ORCAN AMD DESCRIPTION SOPHAGUS Hyperkeratosis IB JUNCTION Table 7C - Continued Individual Histopatliology Findings Albino Rats Receiving 1--2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Males Group 4 1111111111111111111111111 9999999999999999999999999 5555555555555555555555555 Animal 5666667777778888888999955 Number: 8023470234670124678248974 XXOXXXXXXXXXXXXXXOXXXXX X p XX0XXXXXXXXXXXXXX0XXXX0XX NUSUAL LESIONS Hemanglosarcoma Hammary Gland Fibroadenoma Mammary Gland Adenocarcinoma Fibroma Squamous Cell Carcinoma (Submandibular Lymph Nodes) Fibrosarcoma Liposarcoma HYMUS Thymic Carcinoma ERVICAL LYMPH NODE RACHEA Nonsuppurative Tracheitis P p p ppp p p p X 0 XX pp X XXXXX XX X p pp p x ARATHYROID Hyperplasia p 1 Cn ** ' no 181880 CONFTDFNTTAJ Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION Animal Number: Group 1 11111111111111111 99999999999999999 22222222222222222 56667777778888999 301202468923794 7 9 BRAIN Lymphocytic Leukemia Indentation from Pituitary Malacia (Cerebrum) XX XXX X X X ppP p SPINAL CORD X X 0 X X XXXXXOXXXXXX PITUITARY Adenoma Lymphocytic Leukemia Microcysts X X0 0X X PPPP p pp Pp p P pp THYROID X X X X X XXXXXXXOOXXO ADRENAL Pheochromocytoma Lymphocytic Leukemia Medullary Cell Hyperplasia Vacuolar Degeneration of Cortex Sinusoid Ectasia Congestion Hematocyst HEART Lymphocytic Leukemia Atrial Thrombosis Foci of Mineralization Nonsuppurative Myocarditis DO 131 RBI CONFIDENTIAL XXX X P PP PPp Pp p X p p XXX p p pp ppp p p p XXX XX P XXXXX p 22 XX p Table 7C - Continued Individual Hlstopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Females ORGAN AND DESCRIPTION Animal Number: Group 1 11111111111111111 99999999999999999 22222222222222222 56667777778888999 30120246892379479 LUNG Lymphocytic Leukemia Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Suppurative Necrotizing Pneumonia Congestion Bronchiectatic Abscess Formation Mineralization Focal Pneumonitis Aspirated Blood P 3 23 2 22 32322222 2 P PPPP P PPPPP PPPP P P P P SPLEEN Lymphocytic Leukemia Extramedullary Hematopoiesis STOMACH Acanthosis Hyperkeratosis Peritonitis Focal Ulceration Gastritis Metastatic Calcification of Gastric Mucosa Submucosal Edema Congestion XXXX 0 XXXX X0 XX P P pp X 0 XX xxxxoxxx Pp Pp P Pp P P DO 13188? CONFTDFNTTA! Albino Rats Table 7C -- Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION LIVER Lymphocytic Leukemia Nonsuppurative Pericholangitis Bile Duct Proliferation Microgranulomas Congestion Vacuolated Hepatocytes Hepatic Necrosis Foci of Altered Cells Fatty Metamorphosis Extramedullary Hematopoiesis Hepatocytlc Degeneration KIDNEY Lymphocytic Leukemia Chronic Interstitial Nephritis Proliferation of Renal Pelvic Epithelium Congestion Calculi in Renal Pelvis Focal Mineralization SMALL INTESTINE LARGE INTESTINE Nematodlasls Animal Number: Group 1 11111111111111111 99999999999999999 22222222222222222 56667777778888999 301202468923794 7 9 P 22 3 2 2 2232 P PPPP P P PP P PP PP P PP P P P P 22 2 P PPP P P 3 21 P PP P PPP PPPPP P PP P P 2 PP PPPPP PP 1 xxxxxoxxxxxxxoxxx X 0 X X XXX XX XX0XX 0 00 131883 f-ONF T DFNT TA1 Table 7C - Continued Individual Histopatliology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Females ORGAN AMD DESCRIPTION PANCREAS Periarteritis Congestion OVARY Lymphocytic Leukemia Paraovarian CyBts UTERUS Endometritis Cystic Endometrial Hyperplasia Endometrial Polyp Hemorrhagic Necrotizing Metritis MESENTERIC LYMPH NODES Lymphocytic Leukemia NERVE MUSCLE EYE BONE MARROW Lymphocytic Leukemia Animal Number: Group 1 11111111111111111 99999999999999999 22222222222222222 56667777778888999 301202468923794__ 7 9 XXXXXOXX XXXXOXXX P P XXXX 0XXXXXXX0 p XX p XXXX XXX X XX pp p pp p p pp p XXXX oxxxxoxxoxxx p oxxxxxxxxxoxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxx XXXX xxxxxxxxxxxx p tjo CONF I^7B84 Table 7C - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Females ORGAN AND DESCRIPTION MAMMARY GLAND Active Galactocele SKIN ESOPHAGUS RIB JUNCTION UNUSUAL LESIONS Mammary Gland Fibroadenoma Mammary Gland Adenocarcinoma INTESTINAL TRACT Congestion PARATHYROID Hyperplasia URINARY BLADDER Group 1_______ 1 1 11111 11111 11111 9 9 9 9 9 9 9 9 99 9 9 9 9 9 9 9 2 2 2 2 2 2 2 2 22 2 2 2 2 2 2 2 Animal 5 6 6 6 7 7 7 7 7 7 8 8 8 8 9 9 9 Number: 3 0 1 2 0 2 4 6 8 9 2 3 7 9 4 7 9 P PP P XXXXXXXXXXXXXXXXO xxxxxxxxxxxxxxxxx XXXXXXX000XXX00X0 pp pp PP p PPPP p pp p p p xxxxxxxxxxxxxxxxx DO 101885 CONFTDFN 1 TAl Table 7C - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibroino-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Females ORGAN AND DESCRIPTION LIVER Nonsuppurative Pericholangitis Bile Duct Proliferation Congestion Basophilic Hepatocytes Vacuolated Hepatocytes Hepatic Necrosis Foci of Altered Cells Extramedullary Hematopoiesis Peliosis Hepatls KIDNEY Chronic Interstitial Nephritis Proliferation of Renal Pelvic Epithelium Congestion Calculi in Renal Pelvis Renal Tubule Epithelial Hyperplasia STOMACH Acanthosis Hyperkeratosis Focal Ulceration Hemorrhage Basal Cell Activity Group 2___________________________________________ 111111111111111111 999999999999999999 333333333333344444 Animal 777788888999900000 Number; 257813478378__ 9__ 0--1--3--4--6 00 2 22 22 P P PP P 2 2 PP PP 2 PP 22222 222 22 P PP P i pr PP P P P ON>' I PP PP P P P P PPP PP PP 00 21 P PP P PPPPPP P PP P *0 ^ XXXXXXX0000X X Pp pP pp P Pp P pp X no )rnasf> f.ONF TOFNT T At Albino Table 7C - Continued Individual Histopathology Findings Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION LIVER Malignant Lymphoma, Histiocytic Type Nonsuppurative Pericholangitis Bile Duct Proliferation Congestion Hepatic Necrosis Hepatocytic Degeneration Cholangiectasis KIDNEY Chronic Interstitial Nephritis Proliferation of Renal Pelvic Epithelium Congestion Calculi in Renal Pelvis STOMACH Focal Ulceration Hemorrhage Group 2 - Continued 11111111 99999999 44444444 Animal 01111112 Number:804 56890 0 P 1 33 1 33 P PPPP P P P 0 1 P PPPP P PP PPP P PPPP 00XX P PPP P PPP no 131887 f.ONF I DFNT J Al Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION Animal Number: Group 3 1111111111111111111 9999999999999999999 4445555555555555555 9990000111111122334 2 5 9 0 2 3 5 0 1 2 5 7 8947689 LIVER Granulocyte Leukemia Nonsuppurative Pericholangitis Bile Duct Proliferation MicrogranulomaB Congestion Basophilic Cells Vacuolated Hepatocytes Hepatic Necrosis Foci of Altered Cells Extramedullary Hematopoiesis P 232 2 22 22 23 2 22 22 P P PPP P PP P 0 22 22 PP 0 PPP P P PP P PP P PP P PP KIDNEY Granulocytic Leukemia Hematocyst Chronic Interstitial Nephritis Cortical Cyst Proliferation of Renal Pelvic Epithelium Congestion Calculi In Renal Pelvis Megalocytic Cells (Renal Tubules) X P PP PP 1 P PP P P P PP 00 P 15 P PPP PP PP 12 P PP P STOMACH Focal Ulceration Hemorrhage XXXX XX XXXXX0XX p pp p pp DO 111888 CONFTDFNT TAi Albino Rats Table 7C -- Continued Individual Hlstopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION BRAIN Indentation from Pituitary Internal Hydrocephalus SPINAL CORD PITUITARY Adenoma Mycrocysts THYROID ADRENAL Cortical Carcinoma Vacuolar Degeneration of Cortex Sinusoid Ectasia Congestion Hematocyst HEART Myocardial Fibrosis Atrial Thrombosis Endocardial Fibrosis Eplcardltls Group 4 11111111111111 99999999999999 66666666666666 Animal 11111222223344 Number: 35689046790901 X X X X X X XX XXX PP p XXXXXXXXXXXXXX XX XX XXX pp pP p pp p XXOXXXXXXXXXX X X P PP PPPPPPPPP PP PP PPP PPPPP P P P PP PPP XX0X X XX 2 P P PP P P no 1 3 J tfft9 CONF r^>FNrr^i I OUi' l Albino RatB Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION LIVER Neoplastic Nodule Malignant Lymphoma, Histiocytic Type Nonsuppurative Pericholangitis Bile Duct Proliferation Congestion Basophilic Hepatocytes Vacuolated Hepatocytes Hepatic Necrosis Foci of Altered Cells Fatty Metamorphosis Extramedullary Hematopoiesis Pellosis Hepatis Hepatocytlc Degeneration Cholangiectasls Pigment in Kupffer Cells KIDNEY Renal Tubule Adenoma Chronic Interstitial Nephritis Cortical Cyst Proliferation of Renal Pelvic Epithelium Congestion Calculi in Renal Pelvis Megalocytlc Cells (Renal Tubules) Group 4 11111111111111 99999999999999 66666666666666 Animal 11111222223344 Number: 35689046790901 P P 22 22 22 22 PPPPPPPPP P PP PP PP PP P PP P 32 3 PPP PP P 2 2 P P 12 3212 22 PP P P PPP PPPPPPP PPPPP P P PPP PP PPPPPPPPP P P P 131890 conftdfnttai ______________ Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Cbloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION SMALL INTESTINES LARGE INTESTINES Nematodiasis PANCREAS Lobular Atrophy OVARY Malignant Lymphoma, Histiocytic Type Ovarian Cysts UTERUS Endometritis Cystic Endometrial Hyperplasia MESENTERIC LYMPH NODES Malignant Lymphoma, Histiocytic Type EYE Animal Number: Group 4 11111111111111 99999999999999 66666666666666 11111222223344 35 68904 6 7 9 0901 xxoxxxxx 0 X X X 0 X xxxxxxxx OX 0 XX p XXXXXXX X XX p X XX XXX XXXX p XXX X0 p XXX X X X XXX p pp pp xxoxxxox 0 X X X X p xxxxxxxx X X X X X X LUNG Malignant Lymphoma, Histiocytic Type Metastatic Mammary Gland Adenocarcinoma Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Suppurative Necrotizing Pneumonia Congestion no 131891 OONFTDFNT TAl 32 2 PP 0 _ ___ __ P P 3 3 32232 2 33 P PPPPPPPPPPP o* Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION STOMACH Squamous Cell Papilloma Squamous Cell Carcinoma Acanthosis Hyperkeratosis Focal Ulceration Hemorrhage Basal Cell Activity Submucosal Edema BONE MARROW MAMMARY GLAND Active Galactocele SKIN ESOPHAGUS RIB JUNCTION UNUSUAL LESIONS Mammary Gland Fibroadenoma Mammary Gland Adenocarcinoma Zymbal Gland Carcinoma Malignant Lymphoma, Histiocytic (Left Shoulder) 00 131R9? CONFJOFNTTA1 Group 4 11111111111111 99999999999999 66666666666666 Animal 11111222223344 Number: 33689046790901 XX 0 P PP PP PP PPP P PP PP P P P PP PP PP PP PPPPP P PP X XOXXXXXXXXXXX 0 p p ppppp pppp 0 xxoooxxxoxxxx X XOXXXXXXXXXXX X xoxxxxxxxxxxo p pp p ppp pp p p p t Ooo' t Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dlbromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Ueeks ORGAN AND DESCRIPTION CERVICAL LYMPH NODE Lymphoretlcular Cell Proliferation Congestion TRACHEA Nonsuppurative Tracheitis URINARY BLADDER SPLEEN Malignant Lymphoma, Histiocytic Type Extramedullary Hematopoiesis Contracted NERVE MUSCLE Degenerative Myopathy Animal Number: Group 4 11111111111111 99999999999999 66666666666666 11111222223344 356890467909 0 1 P P p XXXXXXXXXXXXXX XX0 P X0 pPP XXXXXXXXXXXO X X XXX XXX XXXX0XX P H) 1 rj 131R93 C'ONFrOFNTTAi Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION BRAIN Nonsuppurative Meningitis SPINAL CORD PITUITARY Adenoma THYROID ADRENAL Cortical Adenoma Cortical Carcinoma Vacuolar Degeneration of Cortex Sinusoid Ectasia Hematocyst HEART Myocardial Fibrosis Atrial Thrombosis Animal Number: Croup 4 - Continued 1111111111111 9999999999999 6666666666666 4444455555556 2 5 6__ 7 8 0 1 2 3 6 8 9 0 XX XXXXXOOXXX P XXXXXXXXOOXXX XXX XXOOX X pp p p XXXXXXXXOOXXX X 00 p p pp ppp p ppp pp ppppp ppp ppppp XX XXX 00XX0 2 pp LIVER Neoplastic Nodule Malignant Lymphoma, Histiocytic Type Hemanglosarcoma Nonsuppurative Pericholangitis Bile Duct Proliferation Microg ranuloraas fnnopa t i or* fJO 131894 CONF 7DFN T T Al 00 P 23223 2 22 2 P O D D D T> D p 2 2 p 1 ~-j 0 1 Albino Rats Table 7C - Continued Individual Histopathology Findings Receiving 1--2-Dibromo--3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AND DESCRIPTION LIVER - CONTIIRJED Basophilic Hepatocytes Hepatic Necrosis Foci of Altered Cells Extramedullary Hematopoiesis Pellosls llepatis Hepatocytic Degeneration KIDNEY Renal Tubule Adenoma Renal Tubule Carcinomas, Unilateral Renal Tubule Carcinomas, Bilateral Malignant Lymphoma, Lymphocytic Type Chronic Interstitial Nephritis Proliferation of Renal Pelvic Epithelium Congestion Calculi in Renal Pelvis Renal Tubule Epithelial Hyperplasia Megalocytlc Cells (Renal Tubules) SMALL INTESTINE LARGE INTESTINE Nematodlasis PANCREAS Lobular Atrophy no 131 BOO CONF TDFNT FAI Group 4 - Continued 1111111111111 9999999999999 6666666666666 Animal 4444455555556 Number: 2567801236890 P PP PP P PP PP P P P PP PP 00 P P PP P 22 23 1 P PP P P PP P P P PP P P P PP P PP PP P P P PP X X X X X x.xxooxxx XXXXXX X0 p XX XXXX X X00X XX PP Albino Rats Table 7C -- Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices Females for 104 Weeks ORGAN AMD DESCRIPTION OVARY Malignant Lymphoma, Lymphocytic Type Ovarian Cysts UTERUS Endometritis Cystic Endometrial Hyperplasia Hydrometra Endometrial Stromal Sarcoma MESENTERIC LYMPH NODES Congestion NERVE MUSCLE Malignant Lymphoma, Histiocytic Type EYE LUNG Malignant Lymphoma, Lymphocytic Type Malignant Lymphoma, Histiocytic Type Peribronchial Lymphoid Hyperplasia Perivascular Lymphoid Hyperplasia Congestion Hemosiderin-laden Macrophages D 1-31896 CONF T DF N r F A( Group 4 - Continued ~ 1111111111111 9999999999999 6666666666666 Animal 4444455555556 Number: 2567801236890 XXX 0 p pp p p 0 XX X XXX 00 XX pp pp pp p XXX XXX X 0 0 X X X p X X XX X X X X 0 0 X X X X X XX X X X X O 0 X X p X XXXXX XX00XX0 00 p p 32 32 22 3 32 p ppP P 3 PP P l >Mvt I Table 7C - Continued Individual Histopathology Findings Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Females ORGAN AND DESCRIPTION SPLEEN Malignant Lymphoma, Histiocytic Type Extramedullary Hematopoiesis STOMACH Squamous Cell Papilloma Squamous Cell Carcinoma Malignant Lymphoma, Lymphocytic Type Acanthosis Hyperkeratosis Focal Ulceration Hemorrhage Basal Cell Activity BONE MARROW MAMMARY GLAND Active Galactocele SKIN ESOPHAGUS RIB JUNCTION UNUSUAL LESIONS Mammary Gland Fibroadenoma Mammary Gland Adenocarcinoma Circumscribed Fat Necrosis Group 4 - Continued 1111111111111 9999999999999 6666666666666 Animal 4444455555556 Number: 2 5 678 0 1 236890 X X XX00 PP P P P P PP XX p p pp pp p p pp X00 ox p p pp pp p p xxxxxxxxooxxx pp p p pp X X X xxxxxooxxx X X X X x X OX XX X00XX0 XX00XX0 rj0 CONFTDFN 1 TAl P PPPP P p P u> Table 7C - Continued Individual Hlstopathology Findings Albino Rats Receiving 1--2-Dibromo--3 Chloropropane (DBCP) for 104 Weeks Deaths and Moribund Sacrifices Females ORGAN AND DESCRIPTION THYMUS Malignant Lymphoma, Lymphocytic Type CERVICAL LYMPH NODE Malignant Lymphoma, Lymphocytic Type URINARY BLADDER Animal Number: Group 4 - Continued 1111111111111 9999999999999 6666666666666 4444455555556 2567801236890 P P XXXXXXXXXXXXX i I DO 131898 OONFTOFNTTA! Albino Rats Ta! i 7D Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices for 104 Weeks ORGAN AND DESCRIPTION Group 1 Male Females 1 11 9 99 Animal Number: 1 9 5 22 56 75 HEART Malignant Fibrous Histiocytoma P LUNG Malignant Fibrous Histiocytoma P SPLEEN Hemanglosarcoma KIDNEY Chronic Interstitial Nephritis Thickening of Glomerular Basement Membrane (Right Kidney) Embryonal Nephroma, Unilateral Malignant Fibrous Histiocytoma, Bilateral Cortical Cysts Renal Tubule Carcinoma, Unilateral 5 P P P P SMALL INTESTINE Mucinous Adenocarcinoma PANCREAS Hemanglo sarcoma OVARY Fibroma UTERUS Endometrial Stromal Sarcoma SKIN Malignant Fibrous Histiocytoma 131899 30NF TDFNtTAl P Group 2 Male Female 11 99 34 40 22 Group 3 Males Female 1 11 1 999 444 9 5 366 669 2 1 P P P P P P Albino Rats Table 7D - Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices for 104 Weeks ORGAN AND DESCRIPTION TISSUE MASS Mammary Gland Adenocarcinoma Maimnary Gland Fibroadenoma Malignant Fibrous Histiocytoma Malignant Lymphoma, Histiocytic Group 1 Male Females 1 11 9 99 1 22 Animal 9 56 Number: 5 75 Group 2 Male Female 11 99 34 40 22 ______ Group 3 Males Female 111 1 999 9 444 5 3 66 2 669 1 P PP AO 131900 CONFrOFNT TA! Albino Rats Table 7D -- Continued Individual Histopathology Findings Receiving l-2-Dibromo-3 Chloropropane (DBCP) Deaths and Moribund Sacrifices for 104 Weeks ORGAN AND DESCRIPTION __________________ Group 4 Hales 1111111 9 9 9 9 9 99 5 5 5 5 5 56 Animal 6 6 6 7 9 9 0 Number: 5698060 Females 1111 9999 6666 2355 5447 LIVER Hepatocellular Carcinoma Neoplastic Nodule Hemangiosarcoma P PP P P KIDNEY Chronic Interstitial Nephritis Embryonal Nephroma, Unilateral Renal Tubule Carcinoma, Unilateral Renal Tubule Carcinoma, Bilateral Renal Tubule Adenoma Renal Tubule Cell Hyperplasia Focal Mineralization Megalocytic Cells Malignant Mixed Tumor 54 P P P P P 44 PP PP P P P UTERUS Uterine Adenocarcinoma P TISSUE MASS Mammary Gland Adenocarcinoma Mammary Gland Fibroadenoma Fibroasarcoraa P PP P no 131901 CONI r OF NT I Al Table 8 Incidence of Neoplasia Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 and Deaths or Moribund Sacrifices Group No.: No. of Animals Examined: BRAIN Astrocytoma Granular cell blastoma PITUITARY Carcinoma Adenoma THYROID C-cell adenoma C-cell carcinoma Follicular cell adenoma Follicular cell carcinoma ADRENAL Pheochromocytoma Cortical adenoma Cortical carcinoma LUNG Hamartoma Metastatic mammary carcinoma Metastatic squamous cell carcinoma Metastatic hepatocellular carcinoma Male 1 2a 3a 48 46 46 4 41 Female i 2a 3a 4 48 45 47 43 2 11 1 1 12 10 30 22 1 11 1 1 7 43 2 11 3 1 1 1 1 Stomach, kidneys, and liver only were examined in low-and mid-dose rats. 00 13190? 00NF TDFNT T A! i i Table 8 -- Continued Incidence of Neoplasia Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 and Deaths or Moribund Sacrifices Group No.: No. of Animals Examined: HEART Thymic carcinoma LIVER Hepatocellular carcinoma Neoplastic nodule Cystic cholangioma Hemangiosarcoma Metastatic squamous cell carcinoma MULTIPLE TISSUES Malignant lymphoma, histiocytic Malignant lymphoma, lymphocytic Granulocytic leukemia KIDNEY Renal tubule adenoma, unilateral Renal tubule adenoma, bilateral Renal tubule carcinoma, unilateral Renal tubule carcinoma, bilateral Benign mixed tumor Malignant mixed tumor _________ Male ~1 If If 48 46 46 _4 41 1 125 423 1 12 111 6 1 1 27 12 1 11 3 __________ Female U If If 48 4547 CO 1 2 23 1 1 1 1 3 11 1 7 13 2 1 8 Stomach, kidneyB, and liver only were examined in low-and mid-dose rats, b One was in salivary gland. Oo 00/s/p- 5 3]903 TdFNTTA! ) l vj VO I Table 8 - Continued Incidence of Neoplasia Albino Rats Receiving l-2-Dibromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 and Deaths or Moribund Sacrifices Group No.: No. of Animals Examined: SPLEEN Malignant mixed tumor, metastatic STOMACH Squamous cell papilloma Squamous cell carcinoma SMALL INTESTINE Mucinous cystadenocarcinoma PANCREAS Islet cell adenoma Acinar cell adenoma UTERUS Endometrial polyp Endometrial stromal sarcoma TISSUE MASSES Fibroma Mammary fibroadenoma Mammary adenocarcinoma Keratoacanthoma Neurofibroma --J MaleJ3 "45 45 34 41 1 1 1 Stomach, kidneys, and liver only were examined in low-and mid-dose rats. Two of the nine animals also had fibroadenomas. Six of the eleven animalB also had fibroadenomas. no 131904 00NF TDFNT TAl _________ Female U If If 48 45 47 _4 43 2 8 1 5 1 24 9b 2 1 26 llc 000 1 Table 8 - Continued Incidence of Neoplasia Albino Rats Receiving l-2-Dlbromo-3 Chloropropane (DBCP) for 104 Weeks Animals Sacrificed Week 104 and Deaths or Moribund Sacrifices Group No.: No. of Animals Examined: TISSUE MASSES-Continued Myxosarcoma Squamous cell carcinoma Hemangiopericytoma Fibrosarcoma Hemanglosarcoma Liposarcoma Zymbal gland carcinoma Male__________ _1 2a 3a 48 46 46 41 1 12 1 2 1 31 1 a Stomach, kidneys, and liver only were examined In low and mid dose rats, k One was in salivary gland. _________ Female U IE IE 48 45 47 DO 131905 CONFTDFNT I At Table 9 Chemically-Induced Non-Neoplastic Lesions Albino Rats Receiving l-2-Dibromo-3-Chloropropane (D8CP) for 104 Weeks Animals Sacrificed Week 104 and Deaths or Moribund Sacrifices \ / Group No.: LIVER Pellosls hepatls KIDNEY Renal tubule hyperplasia (focal) Megalocytic cells lining renal tubules STOMACH rr Acanthosis Hyperkeratosis Basal cell activity Male_____________ 1234 1 11 14 19 3 5 15 9 33 4 5 15 30 4 5 14 30 2 1 3 12 Female 1234 323 1 1 2 12 1 6 40 2 3 8 28 2 3 6 25 2 1 17 no 131906 CONFTDFNTTAl