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HT®0121118 i i ~ I CTR lOlA I CHRONIC EXPOSURE OF BC3F1/CUM MICE I TO 2R1 CIGARETTE SMOKE

NTl0121119 TABLE 1 CHRONIC INHALATION OF 2R1 CIGARETTE SMOKE IN BC3F1/CUM MICE: DISPOSITION OF ANIMALS AFTER SMOKE-SHAM EXPOSURES STOPPED ; ~ ~ Series Date on Test Date Smoke- Sham Treat- ment Stopped Number Alive When Treat- ment Stopped Number Alive 9/3/81 ~ 1,2 9/18/78 10/24/80 Smoke 80 0 Sham 58 1 Shelf 0 3,4 10/37/78 11/21/80 Smoke 110 4 Sham , 80 3 Shelf 0 5 2/5/79 3/20/81 Smoke 110 46 Sham 70 28 Shelf 15 0

1 a TABLE 2 ,Continued) CHRONIC INHALATION OF 2R1 CIGARETTE SMOKE IN BC3F1/CUM MICE DISPOSITION OF ANIMALSa Third Year Cumulative Chemicalb Exp4sure Number On Test Diagnosed In Processing No Necropsy Diagnosed In No Processinge_ Necrops None 2R1 Smoke 2053 284 44 4 892 49 1003 None Sham 1014 201 28 2 597 30 341 None None 449 - 209 8 19 361 8 80 DaP 2R1 Smoke 320 5 0 1 226 0 92 BaP Sham 260 10 1 0 208 3 48 BaP None 130 Od Od Od 106 0 24 aSince September 1978. data as of 9/1/81. bxntratracheai instillations once per week for three weeks prior to SEM II exposure; 1.2 mg Ben2o- (a)pyrene, BaP, in 0.02 ml of a 0.2$ gelatin-saline solution was given per instillation. ~ ® O ~ Na cConditions for smoke exposure consisted of 10% 2R1 cigarette smoke; 20 seconds of smoke; alternatiza with 40 seconds of air for a period of 6-8 minutes. Five such exposures were given each day. Sharv,". exposure was the same but without smoke. ~ dOff test. e7iears 2 and 3 only.

! TABLE 2 CHRONIC INHALATION OF 2R1 CIGARETTE SMOKE IN BC3F1/CUM MICE DISPOSITION OF ANIMALS`1 First Yeard Second Year Chemical° Exposurec Number On Test Diagnosed In Processing Necropsy Diagnosed In Processing Necropsy None 2R1 Smoke 2053 157 (59) 972 451 5 27 None Sham 1014 81 (14) 320 315 2 19 None None 449 4 ( 0) 1a 148 0 43 BaP 2R1 Smoke 320 109 ( 2) 84 112 0 7 BaP Sham 260 63 ( 1) 37 135 2 11 BaP None 130 6 ( 0) 8 100 0 16 aSince September 1978. Data as of S/•1/R1. b=ntratracheal instillations once per week for three weeks p:ior to SEM II exposure; 1.2 mg benzo- (a)pyrene, BaP, in 0.02 ml of a 0.2% gelatin-saline solution was given per instillation. CConditions for amoke exposure consisted of 10% 2R1 cigarette smoke; 20 seconds of smoke alternating with 40 seconds of air for a period of 6-8 minutes. Five such exposures were given each day. Sham exposure was the same but without smoke. dDuring the first six months of the experiment approximately 20% of the animals (animal numbers ending in 3 or 8) had their tissues saved at necropsy. Only 10% (animal numbers ending in 3) were processed for histopathologic diagnosis. Continued ® I I

t TABLE 3 SELECTED SUMMARY OF LUNG HISTOPATHOLOGY IN BC3F1/CUM FEMALE MICE AFTER 2R1 CIGARETTE SMOKE, SHAM EXPOSURE OR NO EXPOSURE, WITH OR WITHOUT BENZO(a)PYRENE TREATMENT Treatment Total Number Examined LUNG DIAGNOSIS Negative/Normal Min. Alv. Hyperplasia Alv. Non-compress. Nodule Alv. Compreasing Nodule Adenocarcinoma Squamous Metaplasia Sqaumous Neoplasm Squamous Cell Carcinoma Pigmented Alv. Macro, AccU.m. Alv. Macrophage A.cum. Congestion Bronchiolitis (para, peri) All Lymph. infiltration All Pneumonia, etc. Granulomas Lymphosarcoma Leukemia (+ infiltrates! Reticulum Cell Sarcoma Carcinomas, Sarcoma Other Malignant Metastatic Carcinuma Metastatic Sarcoma Invasion, Vascular Invasion Adenoma Hemorrhage Autolysis (PMA) Adenomatosis Pigment Deposition Vasculitis, Perivasculitis 2R1 Smoke Sham No Exposure BaP + 2R1 Smoke BaP + Sham BaP + No Exposure 875 581 347 224 193 102 421 274 148 22 13 2 26 11 5 55 64 19 19 12 13 55 66 37 14 8 9 66 80 58 15 6 15 85 87 72 0 0 0 6 5 4 0 0 0 0 0 0 0 0 0 2 6 3 149 3 2 114 5 0 10 16 17 23 23 24 160 147 28 34 32 3 10 10 6 6 3 0 35 36 35 4 3 1 3 6 3 7 4 5 5 7 9 1 0 0 23 28 27 3 0 0 15 17 15 1 0 2 1 0 2 0 0 0 2 0 1 11 7 15 0 0 0 0 0 4 3 0 2 2 0 0 13 11 14 1 0 1 0 0 0 7 0 10 0 0 0 3 5 0 29 14 12 4 1 1 5 3 12 0 3 3 0 0 0 2 1 0 0 0 0 0 1 1 1 4 2 0 1 0

TABLE 4B SUMNART OF SELECTED LESIONS IN OClFI/CUN FENALE ~i1CE AFTER CHRONIC EXPOSURE TO 2R1 CIGARETTE SMOKE Serfes 3, 4 on test 10/18 SEP1raRFR 9e 19q1 BEERS Op TES1: 4 NEEKS ENDIN6 4 8 12 16 20 24 2R 32 36 40 44 48 52 56 60 64 611 77 76 Ro --.-.--.-----.------.---..-.-----..---.--.-..---------------------•---------.---.---.-------------- ----------------------------- --- I NUNBER OF ANIMALS AT RISN 842 793 680 666 6S1 576 534 S10 4AA 495 435 411 397 3Ai 362 354 346 333 325 303 TOIAL NUNBER of OEA7N4 49 113 14 3" 55 42 24 24 31 20 23 1S 10 ?9  9 13 R 92 13 NU/IDEN AwIMALS NoT N[CROPSIED 43 106 11 31 52 33 19 22 29 18 19 9 0 0 1 2 2 0 5 1 NUaBER OF ANIMALS pECROPSI[0 6 7 3 4 3 9 5 2 2 2 4 11 10 75 7 6 11 B 17 12 ACCIOENTAt D[AIN/A/iNECR0PS1[a 4 4 2 0 0 1 5 0 1 0 I 1 1 9 1 0 1 J N n FQUNO OEA04011 NLCROPSIED 2 3 1 4 3 B O 2 1 D S !0 8 15 S S A 9 1• 1? MORIBUNO-R1lLE0GN11pECWOP51[D 0 0 0 0 0 0 0 0 0 2 0 0 1 1 1 1 2 0 0 0 TEST SACRIFICED061INCCROPSIED 0 0 D 0 0 0 0 0 0 0 D 0 0 0 0 0 0 0 0 0 t 4C6ATtY[/NORwAL 5 0 2 3 0 1 4 p 1 1 3 4 7 2D 6 3 1 6 v ? ?11N. AL~. HTPERPLASIA 0 0 0 0 D 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 ALY. NOp-CONPRESS. NODULE 0 0 0 0 0 0 0 0 0 0 D 0 0 0 0 0 1 0 0 0 AIY. COaPRESSIN6 NODUiE o 0 0 0 D 0 0 0 0 0 0 0 0 D o o n 0 0 0 ADENOCARCI~IOMAS 0 0 0 0 0 0 0 0 0 0 0 0 0 O 0 0 0 0 0 0 SOUIa9US N[TAPLA8TA 0 4 D O 4 0 0 0 0 9 0 0 0 0 0 0 0 0 O C SDUANOUS N[OPLASM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SOUANOUS C E L L CARCIMONA 0 0 0 0 •0 0 0 0 0 0 0 0 0 0 o 0 0 D D 0 paaA 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 1 0 0 2 ~ Alr. NAa,OOPHA6E ACCUN. 0 0 0 D 0 0 0 0 0 0 0 0 0 0 0 0 D o 0 0 CON6[S110N 1 7 1 1 3 2 1 0 1 0 1 6 2 S 1 3 3 0 3 ORONC1110L1T15 IPARA.PER11 0 0 0 0 D 0 0 D 0 0 0 0 0 0 0 0 0 D 0 ~ ALL LTaPH. INFILTRAi10p 0 1 O 0 0 0 0 0 O 0 0 0 0 0 n 0 0 0 1 -To ALL PNEUaON1A [TC. 0 0 0 0 0 0 e 0 0 D 0 ~ 0 0 D 6 0 D 6 ® GRANULOMAS 0 0 0 0 0 0 0 D 0 0 0 0 0 0 O 0 D 0 0 ~ LTavaesARCOae o 0 D o 0 0 o D o 0 0 0 0 0 0 0 0 0 1 0-a iEUKENIA /• 1N/ILTRRIESI 0 D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 2~ REFICULUN CELL SARCONA O 0 0 0 0 O 0 0 0 0 0 0 0 0 0 ~ n D n ~r+ I CARCINONASa SARCORAS p 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D 0 n 0- OTIRR aALIGNANT 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0~ /IETASTATIC CARCINOMAS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D 0 0 ~ NETASIAT IC SARCONAS 0 0 0 0 0 ~i 0 ' 6 I 0 ~~ 'u 0 0 0 0 a INRAS10p• OASCULAR 1WASION 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 9 11~ AD[NONRS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 79[NORRHAGC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 AOTOLTSIS iPNAI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D 0 1 0 1 0 AOENOMATOSIS o D o a o 0 0 0 0 0 0 0 0 0 9 0 n n 0 n Pi6MENi DEPOSIl10p 0 0 0 0 0 0 0 0 0 0 0 0 O 0 0 0 0 0 0 0 MASCULIT139 PERI4A301.11116 0 O 0 0 1) 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Ai1na1 audit of e.periloentel data to be completed by 12181. Continued . 0

TABLE 4C Series 5 on test ~i SUMMARY OF SELECTED LESIONS 10 BC3F1/CUM FEMALE NICE SEPIENRTP 5. 19A1 AFTER CHRONIC EXPOSURE TO 2R1 CIGARETTE SNOREa ~ NEEKS ON 7EST0 • B[EKS ENOIN6 6 Q 12 16 20 29 2e 32 40; 90 99 qB 62 56 60 60 6R 72 76 Re I --..----------------N------...------------------------___-_--______-_____-_____---__--_______-_-____ -_-_-__--_-------------------- NUNBER OF ANiMALS DT BiSN 359 292 265 259 252 296 294 231 235 231 222 220 216 210 210 203 201 197 1R% TOTAL NUNBER oF DEATNS 67 27 7 6 6 2 S o 4 q 2 a 2 e 7 2 q 13  NURBEP NiNALS N09 NECPOPSlCO 61 29 7 3 6 1 3 Q 1 7 D 7 1 1 6 0 0 1 0 NUPBCR OF ANINALS NCCROPSI[0 1 ? 0 3 0 1 2 ~ 3 7 2 ? 1 3 1 2 9 12 3 ACCID[UTAL DEATNfAfIN[CPOPD1tD 0 1 0 2 0 1 0 1 1 0 1 1 o O o Q 0 0 0 FOUNO 0[ADTD)i NECRaP81E0 0 1 0 1 o Q Q 3 2 7 1 1 1 3 0 2 ~ tl 3 NORIBUNO-NILLEOTRIiNECROPSiEO 1 0 0 0 0 0 9 0 D 0 0 0 0 0 1 0 0 1 0 BEST SACRiFOCEDiQ1iNECROPSI[D 0 0 D D 0 0 0 0 0 0 0 0 0 0 4 D n 0 0 N[6ATIVCONOPNAL 0 2 Q 3 O 1 f 1 1 6 1 1 1 7 0 2 2 7 2 N1N. ALtl. NTPERPLASIA 0 0 0 0 0 0 0 0 0 0 0 D 0 O 0 ~ p 0 n ALV. NON-CONPRESS. NODULE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Q Q 0 A ALT. COPPPESSING NODULE D 0 0 0 0 0 0 0 D 0 0 0 0 0 0 0 0 0 0 ADENOCARCINONAQ 0 Q 0 0 0 0 0 0 0 0 0 D 0 O 0 0 0 0 0 UApOUS N[IAPLASTA S 0 0 0 0 D Q 0 0 0 0 0 0 0 0 0 0 0 0 0 UANOUS NEOPLASN 0 0 0 0 0 0 0 0 Q 0 0 0 0 0 0 0 0 0 0 SOUApOOS CELL CARCINONA 0 /- 0 0• 0 Q 0 0 0 0 0 0 0 0 0 0 0 0 0 PAwA 0 0 0 0 0 0 0 a 0 D 0 0 0 0 0 0 0 9 p ALV. NACRDPNAQ[ ACCUN. o Q 0 0 0 0 0 0 0 0 o v o Q 0 0 0 0 0 CONCFS11oN o O 0 0 0 0 0 s 2 1 f s o 1 1 0 1 S 1 DRONCRIOL111S lPARA.PER11 O 0 0 0 0 0 0 0 0 0 0 Q 0 0 0 p 0 D Q ALL LTNPN. INi1LTRATION 0 0 0 0 0 0 0 O 0 0 0 0 0 0 0 0 0 1 0 ALL PN[UNON l n E TC . 0 0 0 0 0 0 0 0 0 0 0 0 0 Q o o D n n BRANULORAS 0 0 0 0 O 0 0 0 O 0 0 D 0 0 0 0 0 0 O LINPNOSARCONA D 0 0 0 0 0 0 0 0 0 0 Q 0 Q D 0 0 n 0 9.EUPENTA es INFILTRAT[81 0 0 0 0 0 0 0 0 0 D 0 O 0 0 0 0 1 0 O RET ICULUN CELL SARCONA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D CAPCEMONAS"SARCONAS 0 0 D 0 D 0 0 0 Q 0 0 0 0 0 0 0 0 p 0 01HER MALlGNANT n 0 a 0 0 0 0 0 0 0 0 0 0 D 0 3 0 n 0 NETASTATIC C9RCINONAS o 0 a o 0 o D o o Q D o 0 0 0 0 0 o n NETASTATIC SARCOrAS 0 0 0 0 0 0 D a 0 0 0 0 0 a 0 0 0 0 0 INVASION• VASCULAR INVASION D 0 0 0 0 0 C 0 0 0 0 0 0 0 0 0 0 0 0 AOS NOnAS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Q n 0 0 Is~RORPnAGE 1 0 n 0 0 1 0 Q 0 0 0 0 0 0 0 0 0 1 0 AUTOLYSIS EPNAT 0 0 a Q 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Q AOENONATdST4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 R 0 P16NENT DEPOSITION 0 0 D p 0 0 O 0 0 Q 0 0 0 0 0 0 0 0 0 YASCULITIS. PER:VASCULITTS n 0 0 0 0 0 0 0 0 P 0 0 0 0 0 0 0 0 0 aF!nal a0d1t oF exper:Nental data 6o be co®pleted by 12181. Continued

TABLE 4A SUMMARY Of SELECTED LE`IOMS IN BC3FIICUN FEMALE NICE AFTER CHRONIC EXPOSURE TO 221 CIGARETTE SMOkE Series 1. 2 on test 9/78 SIP1FRBr11 S. 19A1 YEERS ON FEST; 4 NEERS ENDING 4 B 12 16 20 24 26 32 36 40 49 411 57 56 60 69 68 7? 76 pn .---.-...-.-----.--.-.------...-..-.--.-.-.......-....----..........-----...........-.----------_--- -------------------_--.--_-__-- NUMBER 0F ANIMALS AT RISR 960 771 685 57T 551 505 969 419 312 393 300 288 279 268 256 291 227 222 215 200 TOTAL NURBER OF OEATMS 09 06 198 26 96 36 55 92 29 35 20 19 6 12 15 14 5 1 15 11 NyMBER A0IMALS NOT NECROPSIEO 80 77 101 23 03 33 48 37 74 32 20 f0 0 1 2 3 0 P 9 4 NUwBEa OF AN7NALS RCCROPSIEO 9 9 T 3 3 1 7 5 4 3 0 4 6 71 13 11 5 1 13 6 ACCIDENTAL OCATNIAI/NECROPSIEO 7 6 3 1 9 0 1 9 1 0 0 1 1 2 3 9 0 1 0 1 FOUND 01711960111 NECROPSIED 1 2 0 2 3 1 6 1 3 3 0 3 5 7 f0 1 5 6 11 S MORIBUNO-RELLC01K11NCCROPSICD I 1 0 0 0 a 0 0 a 0 0 0 0 2 0 0 0 a ? 0 rEST SACRIFTCC0107INCCROPSIED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 NE6ATIOE/NORNAL S A 2 1 2 1 5 5 4 1- 0 2 2 5 B 5 3 2 6 I RIN. ALT. HTPERPLASTA 0 0 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 ~ ALT. NON-CONPRESS. NOpULE ALI/. COrPRESSIN6 MODULE 0 0 0 a 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 9 0 0 0 0 0 0 O 0 0 0 0 0 0 4 i A a AOENOCARCINONAS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 a SOUAMOUS RETAPLOSIA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 9 0 0 SOOAMOUS NEOPLASM D 0 0 0 0 n 0 0 0 0 0 0 0 0 0 N 0 0 0 P SRUAMOUS CELL CARCINOMA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PARA 0 0 0 0 0 0 0 0 0 6 0 1 0 2 0 1 0 0 1 1 ALV. MACROPMaOC ACCUM. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 CONaESTiON 2 1 4 1 1 0 1 0 0 2 0 2 4 4 9 5 2 3 1 3 RRONCMEOLITIS IPARA.PER11 0 0 0 0 0 a 0 0 0 0 0 0 0 0 0 0 0 a a a ALL LtiFPN. TNF ILTRAT IOq - 0 0 0 0 0 0 0 0 a 0 0 0 1 0 0 0 0 0 I 0 ALL PNEUMONIA ETC. 9 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6RaNULONAS 0 0 9 a 0 0 0 e 0 0 O 0 0 0 0 0 0 0 0 0 LTNPMOSARCONA 0 0 0 0 O 0 A 0 0 0 O 0 0 1 0 .1 0 0 0 P LEUREMiA 4s rNFILTRATESI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 P RETrCULUM CELL SARCOMA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 CARCINOMAS, SARCOMAS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 a o 0 OTHER MALIGNANT 0 0 a 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 a 0 METASTATIC CARCINOMAS 0 0 0 0 0 0 0 0 C 0 0 0 0 a 0 0 0 0 n 0 METASTATIC SARCONAS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1NVAS1011. VASCULAR INVASION 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 lOClIORAS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 HEMORRHAGE 2 1 0 0 0 0 1 0 P 0 0 0 0 0 0 0 0 2 1 0 AUTOLTtts ePwol 0 0 a 0 0 0 0 0 0 a 0 a 0 0 0 0 0 0 0 n ADENOMpTOS311 a 0 a 0 0 0 0 o a 0 0 0 0 0 0 0 a 0 0 0 P10MENT DEPOSITION 0 0 0 0 n 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 VASCULIT1Se PERIVASCULITIS 0 0 0 0 0 a 0 a 0 a 0 0 0 0 0 0 0 P p 0 aFlnal audit of eaperimental data to be compl=ted by 12181. Continued 1 1)

TABLE 5C(Continued) SUMMARY OF SELECTED LESIONS IN OC3F1/CUM FEMALE N1CE AFTER CHRONIC SNAN EIPOSUREa Saries 5 on test 2119 SFrTfNP[0 •s, 19R1 NEERS ON rESTC 4 YEEKS LNOIN6 R4 a6 92 "6 100 104 10A 112 116 120 12• 126 152 136 140 144 148 15? 156 Tnl ~-------..-----------------------------------------------------------.------------------------------ -•------------------_----------- NUNBER Of ANIMALS AT R/SR 129 120 125 118 ill 104 9P PB 12 6t 57 50 42 32 30 30 s0 3A e0 .1 n IOTAL NUMBER Oi DLAT115 1 3 7 1 7 6 la 16 0 7 7 A 10 2 0 0 0 0 0 144 NUMBER ANInALS Nq1 N[CROPS/[D 0 0 0 1 0 0 0 0 0 0 0 3 10 2 0 0 0 0 0 •1 1. NURBER OF ANINALS NECROPSIED 1 3 1 6 1 6 10 16 0 1 T 5 0 0 0 0 0 0 0 103 i ACCIOENTAL DEATNIAIiNECROPSIED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 a 0 0 0 0 7 ! f011ND DEADIDIi NCCROPSIEO t 2 2 6 6 9 S 12 7 6 6 5 0 0 0 0 0 0 ~1 1S i , MOROBUNO-RILLEDIRIUNECROPSIEO 0 1 5 0 1 1 5 4 1 I 1 0 0 0 0 0 0 0 0 21 i :EST SACRIF[CEOIOIINECROPSIED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 P G 0 i NERATIME/NOAMAL 0 0 4 3 9 3 4 l0 5 4 3 3 0 0 0 0 0 0 0 52 s MIN. aLO. HTPERPLASIA 0 0 0 0 0 1 0 O 1 0 0 0 0 0 0' 0 0 0 0 0 ALr. NON-COMPRESS. MOOULE 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 ALT. COMPRESS[N6 NOOULE 0 0 0 0 1 0 0 0 1 0 0 1 0 0 0 0 0 n 0 3 AOENOCARCIN071AS 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 SOUAMOUS METAPLASIA 0 0 0 0 a 0 0 0 0 0 O 0 0 0 0 0 0 n a 0 SOUAPOUS NEOPLASR 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SOUAMOUS CELL CARCINOMA 0 0 0 0 •0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PARA 0 0 0 0 0 0 0 a 0 0 0 0 0 0 0 0 0 0 0 1 ALT. NACRBPNAGE ACCUM. 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 a 9 S CoN6ESttoN 1 0 a 1 0 1 0 1 1 0 0 0 0 0 0 0 0 0 0 1+ --~ BRONCMIOLITIS EPAOA0E011 0 0 0 1 0 0 0 0 0 0 0 0 0 P 0 a 0 0 0 1 ALL L1MPM. INFILTRATiON 0 0 0 0 0 1 2 2 0 0 0 0 0 0 0 0 0 0 0 7 ® I. ALL PNEUMONIA ETC. 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 1 O C'd ANULONAS 0 9 a 0 1 0 n 0 0 0 0 n 0 0 0 0 0 0 0 3 ~ LTMPN(ISARCOPA 0 1 0 1 0 1 3 1 0 0 2 0 0 0 0 0 0 0 11 ~ LEUnEMIA Ie INIILTRATESI 0 0 0 0 G I 1 0 0 0 0 0 0 0 0 0 0 a 0 2 RETICULU/I _ELL SAOCON 0 0 0 0 0 a 0 0 0 0 0 a a 0 0 0 U 0 0 0 CARCINOMAS. SARCOMAS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 O 0 0 0 0 0 OFNER IIALIONANT 0 0 0 0 0 ^ e 0 n 0 0 0 0 0 0 A 0 0 n 0 CA t METASTATtC CARCINONAS METASTATIC SARCOMAS 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 2 0 0 0 0 0 0 O 0 0 0 0 0 0 0 0 0 0 4 .i~ i 1NVASION. VASCULAR INVASION a 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 t ADENONAS 0 0 0 a 0 0 D 0 0 a o 0 9 0 0 0 0 0 o D HEM6RRHABE 0 0 1 0 0 0 0 0 0 1 0 1 0 0 0 0 n 0 0 9 AUTOLTStS 4PMAI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 CDENOIIATOSIS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D P/GMEN7 DEPOSITION 0 O_ 0 0 0 0 0 0 0 0 a 0 a 0 0 0 0 0 0 0 YASCuLITIS. PERI4ASCULiTIS 0 0 0 0 0 0 n 0 n a 0 n 0 n 0 0 0 0 0 P °Flnaf audit of experimental data to be eompleted by 12/81. 0

TABLE 4A(Continued) ! Serfes 1. 2 on test ~I SUNNARI OF SELEC'EO LESIONS IN BC3F1fCUN FENALE NICE y/7B AFTEP CHRONIC ENPOSURE TO 2R1 CIGARETTE SNOKE6 SIFTEMAIR 50 14a1 ~4 YEEKS ON TEST: 4 YEEKS ENDING 04 00 92 96 100 104 108 112 116 120 124 128 1!7 136 100 14e 140 197 136 I0T I ----- M.---...---.----------------------------°--'---'----'------------'-°------- ° -------'-'------------------------------------_ NDNBEP. OF AN/NALS AT RISk 1R9 182 170 1SR 134 119 96 04 14 E7 56 44 30 33 70 11 A 4 0 0 }' TOTAL NUNBER OF NATNS 7 12 1? 24 1S 23 12 10 1 11 12 6 5 13 q 3 4 4 0 86 NoRBER ANIMALS NOT NCCR0PS1E0 0 0 3 2 1 3 a 0 0 I D a 0 0 0 0 2 4 0 560 ~ NURBER OF ARIOIALS NCCROPSIED 7 12 9 22 14 20 12 10 1 10 12 6 0 13 9 3 2 0 0 See }~ ACCiDCN1AL DCATIfEAITNECROPSICO 0 0 0 0 0 0 3 0 0, 0 0 0 0 0 0 0 0 0 0 qa ;f FOUND OEA01001 NECROPSIEO 7 9 9 20 0 10 6 10 6 I• 7 3 1 9 T 3 2 0 P h 215 RORIDUND-KILLCDfK1TXECROPSIEO 0 3 0 2 6 2 4 0 1 4 6 3 4 4 2 0 0 0 0 ] 46 TEST SACRIFICE0RO/1NECROPSIEO 0 0 0 0 0 0 P n 0 p 0 0 0 0 0 0 0 a 0 I i 0 NEGATIVE/liORMAL 0 4 3 9 4 7 5 4 1 3 5 1 3 7 5 0 0 0 0 12° NiM" qtt. HTPERPLASIA 0 0 0 1 1 0 0 • D 1 0 0 D 1 0 1 1 0 0 P I aiM. bON-COMPRESS. NOOUL[ 0 0 1 0 0 0 0 0 0 0 1 1 D 0 1 0 R 0 0 . ALO. CORPRF SS iN6 NDDULE 0 0 0 0 0 1 0 0 0 0 0 0 D 1 0 0 0 D 0 3 AOENOCAR C INOMAS 0 0 0 1 0 0 1 1 0 0 0 0 0 0 0 0 0 D 0 i ~ S00ApOYS MCTAPLASTA 0 0 0 D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 soUAROUS N[OPLASp 0 0 0 0 0 0 0 0 0 0 0 a 0 0 0 0 0 0 0 r 0 SOUAROUS CELL CARCINORA 0 0 0 0 • 0 0 0 0 0 0 0 0 0 0 0 0 0 R 0 n PAIIA 1 4 l A 9 7 6 3 3 1 3 3 2 2 0 2 1 0 0 12 ALT. MACROPNA6E ACCUN. 1 0 0 0 0 1 1 0 0 0 1 0 0 0 0 0 0 0 0 S ~ COt16ESTlON 1 3 1 S 2 S 0 0 0 0 0 0 0 0 0 0 0 0 0 97 ; ItRONCN10Li11S IPARAoPERLI 0 0 0 0 0 1 9 0 0 0 1 0 0 0 0 0 0 0 0 ?S ALL LTpPH. [NF ILTRAI lOM 0 1 0 2 0 0 1 0 1 1 0 a 0 2 1 0 0 0 0 i 11 ALL PLSCUMOKIA CTC. 0 e 0 0 D 0 0 0 0 0 0 0 • D 0 0 0 0 0 -4 ~ EAAYULORAS 0 0 0 0 0 0 0 0 O 1 0 2 t 0 0 0 1 0 0 L~ ~ LTNPMOSARCORA 0 1 3 2 0 0 p 0 1 3 1 0 0 0 0 D n 0 0 1sm LEUKERTA t+ Ihi1L1RATESI 2 0 1 0 0 l 0 l • 0 0 0 0 1 0 0 0 0 0 1--% { RETTCULUR CELL SARCONA 0 0 0 0 0 0 0 0 0 D g 0 0 0 0 D 0 n n 4. CARCINONASo SAACORAS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D D 0 0 f II~ ` DiHER NALIBNA7T 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 j kEIASTATT[ CARCTIeONAS o 0 0- 0 0 0 1 0 0 0 0 n 0 0 e 0 0 • n i T-~ NETASTATIC S30COMA4 0 0 0 0 1 2 0 0 0 0 0 0 0 l 0 0 0 • 0 a~ INYA.SION• VASCULAR INVASION 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 • 0 0~ AOENOIIAS 0 0 a 0 0 0 0 0 p 0 0 0 0 0 0 0 0 0 0 0 HENORRHA6E 1 0 0 0 0 0 0 0 1 0 1 D 0 0 ~ 0 0 0 0 1~ AUrOLTStS EPNA1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 e 0 1 AOENONATOSIS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 • P p P18NENT 0190S11I0M 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 vASCULLTISa PERIYASCULITIS 0 0 0 0 0 a 0 a D n 0 0 D n 0 0 n 0 0 n aifezl audit of eaperlWental date ta be Completed by 12/B1. . 0