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313 I. BRL-ORNL COLLABORATIVE SMOKE PARTICULATE DEPOSITION EXPERIMENT J. E. Caton; R. A. Jenkins, M. P. Maskarinec, G. M. Henderson, R. W. Harvey NCI has been sponsoring chronic tobacco smoke inhalation bioassays using the male beagle dog animal model for several years. While chemical definition by ORNL of those bioassays has provided an estimate of the smoke doses offered the animals, current capabilities do not provide for a quantitative determina- tion of the level of smoke particulates actually retained by the animal. In order to address such questions as the effects of nicotine or cannula design on smoke retention, or the efficacy of the use of serum or urine nicotine/ cotinine levels as indicators of retained smoke dose, NCI has been sponsoring a collaborative dosimetry study between Borriston Research Laboratories and Oak Ridge National Laboratory. The design of the experiments is as follows: 60 dogs (3 groups of 20) are being exposed under standard NCI conditions for approximately 200 days. During the exposures, measurements are made on the animals' physiology, and monthly samples of blood and urine are taken. At the time of sacrifice, the animal is exposed (under conventional conditions) to the smoke of a cigarette which has been loaded with several microcuries of 14C-dotriacontane (14C-DTC). DTC is a high molecular weight, long chain hydrocarbon, which is naturally present in tobacco and distills into the cigarette smoke. Other studies have indicated that DTC and overall tar depositions are highly correlated. Immediately fol- lowing exposure, the animal is sacrificed, and the respiratory tract excised. Lung lobes are separated from the bronchial tree. Tissue and final blood samples are sent to ORNL for radiochemical assay. Deposition and distribu- tion of the cigarette smoke tar constituents will be related to the locations

314 of the 14C-DTC label. The three animal groups in the experiment are being exposed according to the following conditions: Group 1: Exposure to a high nicotine (SEB IV) cigarette with a cuffed cannula. Group 2: Exposure to a low nicotine (Code 13) cigarette with a cuffed cannula. Group 3: Exposure to a high nicotine (SEB IV) cigarette with an uncuffed cannula. Comparison of particulate deposition between Groups 1 and 2 should give an indication of the importance of the nicotine concentration in smoke to the relative intensity and site of deposition. Comparison of deposition in Groups 1 and 3 should indicate the differences in smoke retention due to cannula design. Joint responsibilities in this study include experimental design, analysis of blood and urine samples taken throughout the 200 day ex- posure, and reporting. Responsibilities unique to Borriston include animal exposure and physiology measurements during 200 day exposure. Responsibilities unique to ORNL include providing radiolabeled cigarettes and radiochemical assay of sacrifice tissue and fluid samples. Current Status of Experiment. Quite recently, the first group of exposed animals were sacrificed (Group 1). Fluid and tissue samples are being pre- pared for shipment to ORNL. Group 2 sacrifice is scheduled for mid-July, 1978, with Group 3 being scheduled for late August, 1978. We expect to complete tissue and fluid analyses in late 1978, with reporting scheduled for 1979.