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v• r_.---.--~- . H T®012" 1 L0 3. Pharmacokinetics/Metabolism 'I a. Title: STUDIES ON THE DEPOSITION AND DISTRIBU- TION OF CATECHOL FROM WHOLE CIGARETTE SMOKE IN BC3F1/CUM MICE Authors: K.K. Hwang, 0. Sonko, D.R. Dansie, R.E. Kouri, and C.J. Henry S Ut4 MARY I Tritiated-catechol has been used to follow the pharmaco- kinetics and metabolic fate of inhaled catechol in cigarette smoke in BC3FI/Cum mice. The presence of 3H-catechol in the smoke was verified by silica gel chromatography, high performance liquid chromatography, and gas chromatogra phy/mass spectrometry. Mice were exposed to 10% (v/v) 2R1 cigarette smoke on the Walton Horizontal Smoking Machine under standard conditions of 35 ml puff volume, 2 sec/puff, 10 puffs/cigarette. The deposition and distribution of inhaled catechol was determined in all internal tissues, urine a nd feces. Data showed that clearance was occur- ring during the 10 minute srnoKe exposure period. Immediately after exposure, over 50% of the radioactivity was found in the blood, with 10% found in the lung, and "12 $ in the respiratory tract. Over 94% of the inhaled radioactivity was found in the urine 120 minutes after exposure. Less than 0.6% of the total dose was found in the lung at this time. We conclude that cate- chol in smoke is rapidly absorbed, redistributed, and excreted from mice exposed to whole cigarette smoke. Sta*_us: Submitted Status: Submitted Toxicology and Applied Pharmacology, 1981. /1

I ~~.. - - -----~-~ ~,_. - - . Hi®0121101 b. Title: SYNTHESIS OF TRITIUM LABELLED CATECHOL Authors: K.K. Hwang, B. Bhooshan, R.E. Kouri, and C.J. Henry SUr4MARY The preparation of tritium labelled catechol by catalytic reduction of tetrabromocatechol is described. Recrystallization of catechol (U-3H) after silica gel column purification gave 68% yield of the desired product as assayed by high performance liquid chromatography. Status: Accepted for Fublication, Journal of Labelled Compounds and Radiopharmaceu- ticals, 3JS1.

HIg01a11L- c. SUMMARY Title: DISTRIBUTION AND CLEARANCE OF THREE CIGARETTE SMOKE CONSTITUENTS, DOTRIA- CONTANE (DTC), NICOTINE (NIC), AND BENZO(A)PYRENE, (BP), AFTER EXPOSURE OF MICE TO WHOLE CIGARETTE SMOKE Authors: C.J. Henry, A. Lopez, D.R. Dansie, M.D. Avery, C.E. Whitmire, J.E. Caton, J.R. Stokely, M.R. Guerin, R.D. Cur- ren, and R.E. Kouri The internal distribution of three constituents of the particulate phase of whole cigarette smoke was compared in male C3H/Anf Cum mice at various times after smoke exposure. Ciga- rette smoke was generated from reference 2A1 cigarettes contain- ing either 1SC-DTC, 14C-Nic, 14C-BaP using a Walton Smoke Expo- sure Machine under standard conditions of puff duration, puff volume, puff frequency smoke concentration and total smoke expo- sure time. 19C-DTC, 1~C-NIC, 14C-BaP represent the straight chain hydrocarbons, the alkaloids, and the polycyclic aromatic hydrocarbons, respectively, of the total particulate matter (TPM) of cigarette smoke. The yield of TPM and amount of radiolabeled per cigarette were quantified during exposure. The total initial TPM dose as reflected by smoke containing 14C-DTC, 14C-NIC, 1aC-BaP was estimated to be 210, 243, or 145 ug TPM, respective- ly. After a 10 min smoke exposure, the internal distribution of DTC was 69.0% lung, 0.4% larynx, 6.6% head, 19.6% stomach, 5.0% other tissues. For NIC, the distribution was 2.5% lung, 1.2% larynx, 15.8% head, 3.5% stomach, and 77.1% other tissues. For 6aP, the distribution was 24.0% lung, 4.0% larynx, 13.3% head, 13.7% stomach, and 45.0% other tissues. The half-life for internal retention in the mouse was >24 hrs. for 14C-DTC, '0.5 hr. for 14C-NIC, and -1.0 hr. for 14C-BaP. ~ Status: The Toxicologist, 1: 139, 1981; draft of complete manuscript scheduled for 10/81. /Y

J v •J J H1®012110b , d. Title: THE IDENTIFICATION OF CATECHOL AND RELATED CHEMICALS IN URINE FROM BC3F1/ CUM MICE EXPOSED TO WHOLE CIGARETTE SMOKE Authors: K.K. Hwang, 0. Sonko, D.R. Danrie, M. Jaqusiak, S. Huang, R.E. Kouri, C.J. Henry SUMMARY Catecho1,1,2-dihydroxybenaene, is one of the major con- stituents of whole ciga rette smoke. Recently it has been shown that catechol is rapidly excreted from mice after exposure to whole cigarette smoke containing radiolabeled catechol. Urine was collected from these rttice over a two hour period following exposure to smoke. Over 90% of the 3H-label in the urine was not extracted by chloroform-methanol or ethyl-acetate. Following 8-glucuronidase and arylsulfatase treatment of the urine, cate- chol was detected by both ultraviolet spectroscopy and scintil- lation spectroscopy. High performance liquid chrimatography, gas chromatography, and mass spectrometry were employed to iden- tify the urinary metabolites of catechol which were catechol, hydroquinone and 4-methylcatechol. Status: First draft scheduled 11/81. !C