Tobacco Documents Online

47 Intemational Research and Development Corporation The ineidence of pulmonary neoplasms from the present study is prasentad ia the foLloving table. IpCIDENCE OF PiTI2t0tiARY NEOPLASMS Males 300 ppa 3,006 ppa 6,000 ppm 10,000 ppm D®~ ~ DOS SAC DOS SAC DOS SAC DOS SAC (20 (21) (26) (24) (26) (24) (33) (17) (35) (15) ALVEOLAR/BRONCHIOLAR ADENOMAS il 9 13 13 10 18 18 13 19 8 ALVLOLAR/BRONCHIOLAR CARCINOMAS 3 2 1 1 1 4 4 3 6 0 TOTAL PULMONARY NEOPLASMS 14 11 14 14 11 22 22 16 25 (27) (23) (31) Females (19) . (25) (25) (29) (21) (31) (19) - ALVEOLAR/BRONCIiIOLAx ADENOHAS 8 12 14 12 12 15 12 16 13 -- 13 ALVEOLAR/BRONCIiIOLAR CARCINOHAS 0 0 3 0 2 0 2 0 4 0 TOTAL PULMONARY NEOPLASMS 8 12 17 12 14 15 fl4 16 17 13 Lung tumors occur spontaneously in many strains of mice and t:he incidence varies between strain with a higher incidence in the males compared to the females. The neoplasms appear to arise either from the alveolar cells lining the pulmonary alveoli or from Clara cells gound normally within bronchioles. Since these two types of lung neoplasms cannot be easily distinguished between at the light microscopic level, they are usually designated as alveolar/bronchio- lar adenomas or carcinomas. The incidence varies quite markedly between different studies conducted in the same strain of mice in 399-054

48 International Research and Development Corporation the same laboratorT. The historical incidence of alveolar/bronchio- lar Bdenocsas and carcinomas in four, two-7ear chronic studies con- ductcd at IRDC from 1983 to 1985 is presented below. . RIST®RICAL INCIDENCE (2)'OP POIXONARY NEOPLA.SKS IN CD-1 MICE AT IRDC Stud}s Males Total Females Total Adenotaas Carcinomas Adenoaass Carcinomas A 18.2 0.90 19.1 12.7 4.5 17.2 E 44.0 0 44.0 22.0 2.0 24.0 C 28.0 6.0 34.0 14.0 2.0 16.0 D 26.1 8.7 34.8 8.7 2.9 11.6 3. Summarq A variety of nonneoplastic and neoplastic lesions were seen in both sexes across dose levels and the majority of thes: appeared to not be related to the administration of the test article. Inflammation and brown pigffint in the livera of the male mice were more'prevalent in the treated than in the controls and mar have been relatad to the administration of the test article. An increase in lung aeoplasns was present in both the treated males and treated femalas compared to the controls. A dose response, however, was not evident. Prepared Bq: Charles H. Trith, D.V.H., Ph.D. Resident Consy4tin= Pathologist Date Robert G. Ge.il, D.V.1{., A.C.V.P. Diplozate Date Scientific Director of Pathology Division 39"34