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-------- ..; -1olcl~/y5 2. Dosimetry a. Title: THE DOSIMETRY AND DISTRIBUTION OF WHOLE CIGARETTE SMOKE PARTICI'LATES IN INBRED STRAINS OF MICE: COMPARISON OF A LARGE SMOK'r'.-EXPOSURE MACHINE (SEM) WITH A SMALL-CAPACITY SMOKE-EXPOSURE MACHINE (WALTON) Authors: C.J. Henry, C.E. Whitmire, A. Lopez, D.R. Dansie, M.D. Avery, J.E. Caton, J.R. Stokely, R.W. Holmberg, M.R. G uerin, and R.E. Kouri SUMMARY The deposition and the internal distribution of total particulate matter (TPM) of cigarette smoke were examined under conditions of high TPM deposition in the lung:L of mice. Two dif- ferent smoke-exposure systems were used. The smoke-exposure machine (SEM II) is a large-capacity (480 mice) dynamic system In which smoke is routed through the animal containment unit as a continously flowing stream. Mice are restrained about the neck in stock-type holders for nose-only exposure. The Walton Hori- zontal Smoking Machine (Walton) is a small-capacity (12 to 20 mice) static system where the smoke is introduced into exposure chambers into which mice (restained in either stock-type holders or whole-body tubes) respier directly. Both machines were oper- ated under standardized conditions for puff duration (2 sec), average puff volume (35 ml), puff frequency (once per minute), and butt length of cigarette (23 mm). A radioactive tracer (14C-labeled dotriacontane) was used to quantitate the deposition of TPM in tissues of the mouse af ter exposure to smoke. When the Walton machine was used, the deposi- tion of TPM for 2A1 Kentucky refere:;ce cigarettes increased with increasing smoke conc,?ntration and smoke-exposure time but was independent of sex or strain of mouse. Detectable levels of TPM were found in the head, larynx, lungs, and stomach. The distri- bution of TPM among these tissues did not change as the total exposure time increased to 300 sec or as the smoke concentration was increased tc 14.1% (vol/vol). e:egardless of total exposure time or smoke concentration, 73 to 77% of tae TPM was found in the lungs and 88 to 91% of the TPM was contained in the entire respiratory tract. Thus the conditions of 10% (vol/vol) smoke conaentration for 300 sec of total exposure were chosen for com- parison of the deposition and distribution dn TPM from the two smoke-exposure systems. The average deposition of TPM in t,he lungs of BC3F1/Cum mice was 123 and 134 ug after exposure on the Walton and the SEM II machines, respectively. Coefficients of variation for a total of 40 mice exposed on the Walton and a total of 120 mice exposed on the SEM II were 0.20 and 0.09, re- a

nAd121096 spectivley. The percent of total body distribution of TPM for animals exposed on the Walton was 80% in the lungs and 8 68 in the entire respiratory tract; for animals exposed on the SEM II , 70% was found in the lungs and 88% in the respiratory tract. Status: °Pulmonary Toxicology of Respirable Particles° (ed. Sanders, Cross, Dagle, and Mahaffey), Technical Information Center, Springfield, VA, pp. 177-192, 1980. 9

m ~_....-.._ -- Y...._ "f-__ J. ___ ._ - .. 9 ai®o -I 111ig ' b. Title: DEPOSITION AND DISTRIBUTION OF THE TOTAL PARTICULATE MATTER OF CIGARETTE SMOKE IN MICE USING A LARGE-CAPACITY SMOKE EXPO- SURE SYSTEM Authors: C.J. Henry, J.E. Caton, J.R. Stokely, M.R. Guerin, A. Lopez, M.D. Avery, D.R. Dansie, G.M. Henderson, T. Gayle, C.E. Whitmire, and R.E. Kouri SUMMARY I i A newly developed automatic smoke exposure machine (SEM II) was used to generate (1SC)dotriacontane-labeled University of Kentucky reference 2A1 or 2R1 cigarette smoke. The SEM II is a large-capacity (480 mice) dynamic smoke exposure system in which smoke is routed through the animal containment system as a con- tinously flowing stream. Mice are restrained about the neck in stock-like holders for "nose-only° exposure. Using standard smoke exposure conditions, the deposition and internal distribu- tion of the total particulate matter (TPM) from cigarette smoke was determined in F3C3F1/Cum male and female mice. Results show: (a) smoke exposure conditions can be varied so that deposition from 30 to 200 ug TPM/lung can be obtained, (b) 80-90% of the TPM deposition was found in the raspiratory tissues, (c) the mouse- to-mouse variation for TPM deposition in pulmonary tissues was 20%, (d) similar deposition and distribution of TPM was observed in male and female mice, and (e) deposition and distribution of TPr, was not altered in mice exposed to smoke on a daily basis over a 6-month period of time. Status: Published in Toxicology and Applied Pharmacology 58, 399-409, 1981. 9

c. Title: CARBOXYHEMOGLOBIN LEVELS AS A MEASURE OF CIGARETTE SMOKE EXPOSURE IN M1CE Authors: C.J. Henry, L.A. Breth, J..M. Gerhart, D.R. Dansie, H.D. Mullinax, C.E. Whitmire, and R.E. Kouri SUMMARY Status: Final draf t scheduled for 9/81. /0 Carboxyhemogbobin (COt?b) levels have been investigated in mice exposed to whole cigarette smoke under defined conditions. Two methods for detecting blood COHb levels were evaluated. COHb levels were sh,)wn to be dependent upon smoke concentration, total smoke exposure time, total time over which smoke was given, and the time at which the blood samples were taken after exposure. Correlation between COHb levels and pulmonary deposition of smoke particulates was demonstrated using two different reference ciga- rettes. COHb levels were shown to be a non-invasive, reproduc- ible method for measuring and monitoring smoke exposure in mice. R•-

qffa_~__ i~-ThO 11'1G y y Title: PULMONARY LOCALIZATION OF A PART]CULATE CONSTITUENT OF CIGARETTE SMOKE IN MICE Authors: C.J. Henry, J.C. Geihard, S. Gosnell, R.C. Knipscher, A. Lopez, D.R. Dan- sie, L.H. Billups, W.C. Hall, and R.E. Kouri SUMMARY Using cryotomy and autoradiography techniques, the dis- tribution pattern of 14C-dotriacontane (DTC) has been determined within the lunas of mice after inhalation of 14C-DTC labeled whole cigarette smoke. 14C-DTC is used as a tracer for the particulate phase of whole cigarette smoke and is relatively inert in biological systems. The resolution of the 6 um frozen cut sections demonstrated clear detail of pulmonary histology. Loss and/or rearrangement of the organic soluble tracer was mini- -:ized during preparaticn of the tissue sections through use of alcohol fixation and freeze dessication techniques. The auto- radiograms show that immediately after smoke exposure, the label- ed smoke particulates were distributed along the epithelial lin- ing at alveolar septa, bronchioles, and bronchi. Twenty-four hours following smoke exposure, aggregation of the tracer had occurred within lung without affecting distribution. Status: Submitted, Toxicology 8/81. //