Tobacco Documents Online

04/24/91 Review of Levulinic Acid fLAZ HRRC Activity (a:\hrrc9l\lahist.91w) 02/26/86 HRRC APPROVED W. R. Cook's request to do SED & consumer test on cigts w/LA. LA approved up to level of 2% by wt. of tobacco BUT no other tests allowed until additional data obtained: identities & concs. of lactones in LA supplies long-term effects of LA on occurrence & growth rate of tumors in "suitable animal model" study of transfer of LA to smoke & study of effects of product aging on transfer to smoke Test was NFO panel (2-pack, blind, monadic - FFLT pdt topdressed w/ 0, 0.6%, 1.0%, 1.4%, 2.0% LA. FF pdt topdressed w/ 0, 0.45%, 0.75%, 1.05%, 1.50% LA. Scientific Affairs opinion was that up to one pack per day of cigts w/ up to 2.0% LA by wt. could be tested. 01/09/87 HRRC APPROVED J. W. Lawson's request to do focus group testing of cigts w/ L-nicotine levulinate, subject to the restriction that a) smoke nicotine levels (FTC) must not exceed ca. 1.3 mg/cigt and b) purity of nicotine levulinate must be assured. Focus group participants to smoke one (1) cigarette of one of the following types: Brand % Application of Nic:La3 WUL-100 CL-85 N-85 t 1.0 3.0 5.0 1.0 3.0 5.0 3.0 7.0 10.0 Tar, nicotine and CO data for all pdts were supplied.

added to 1st test group. 11/90 Results from R9038 & R9038b used to ok test proposed in R9035. 02/26/91 HRRC APPROVED R9111 (J. C. Walker) to test human anosmics with nicotine and LA such that subjects receive no more than 0.304 mg LA/wk (concs. no higher than 1.47 ppm) and concs. of nicotine no higher than 2.43 ppm. 03/14/91 HRRC APPROVED R9114 (H. H. Gordin). A standard test protocol to be used with HRRC-approved prototypes. Includes Phase I: pre-test questionnaires (may include SMQ, product consumption, DFC), Phase II: smoking of 1 cigt, followed by completion of Body Map, satisfaction scorecard, DFC ballot, Phase III: additional questionnaires & DFC, Phase IV: smoke 1 cigt, complete final DFC ballot. 03/14/91 HRRC approved R9115 (M. R. Savoca) to perform external QDA, internal diagnostic, external; screening, external HSB, external PGT (understood to mean exposure to, NOT MORE THAN 2 PACKS) on a series of ca. 5 mg tar products containing up to 25% by weight of G7-1 with up to 5.65% LA and or 4.0% KDN extract. Approval limited to specific products. Other tests specifically not approved. 04/09/91 HRRC APPROVED R9120 (J. H. Robinson) to perform 1-cigt plasma nicotine study on WINSTON prototype containing 22.5% of G7-18 sheet with ca. 5.6% LA on sheet.

r_ t qcp,l " c A rd -f ~nfjaJ 0 /LlsraC-c.

S7-r ~ra _ Ex A'QL?~s (tia Og, ® OomG1,nqd I " /l.us Om um/ - ~ I ) i

•F r 2 04/15/87 HRRC APPROVED J. H. Robinson's proposal to study plasma nicotine and smoking behavior in smokers on 2 occasions each, separated by 2 weeks. Cigarettes were ones described in J. Lawson's proposal of 1/9/87. Smokers assigned to groups as follows: Group 1 Group 2 Cigt 1 NOW-85 WUL-85 Cigt 2 NOW-85 w/ 10% WUL-85 w/ 5% nic:La3 nic:La3 'Pyrolysis data of nic:La3 provided AMES data on NOW-85 at 0, 3%, 7%, 10% nic:La3 and WUL-85 @ 0, 1%, 3%, 5% nic:La3 showed lowering of dose-response slope w/ increasing nic:La3. 06/09/87 HRRC APPROVED J. C. Walker's proposal to perform human odor- sensitivity tests with nicotine, LA, and nicotine-LA mixtures in air. Max LA conc not to exceed 640 ug/L; max delivery of nicotine not to exceed 1.3 mg. PROJECT WAS DROPPED. 09/29/87 K. F. Cook's proposal to extend testing of LA to ULT, FFLT and FF smokers was tabled. 10/27/87 HRRC APPROVED K. F. Cook's proposal to test cigarettes in 2-pack, blind, monadic tests involving up to 500 smokers per cell of up to 6 cells. ULT, & FFLT smokers to be tested. Products to include NOW-85 (max LA level 14.2% or 69.34 mg/cigt) and WUL-85 & 100's (max LA level 6.2% or 46.13 mg/cigt) Total daily exposure sf smokers to LA limited to 69 mg/day as `estimated by FTC method, and cigts limited to no more than 1.42 mg nic/cigt by FTC method. 10/11/88 HRRC APPROVED R8816 (T. A. Perfetti) to perform SED tests and focus groups on pdts w/ 1% LA in VUL-85 configuration that also contained 2.7% tob. nic. - BUT specifically disallowed use of pdts containing Fagg's tobacco essence. Product descriptions included summaries of materials properties and indicated maximum expected tar and nicotine levels. 03/28/89 HRRC APPROVED R8910 (J. H. Robinson) to perform plasma nicotine study of two XGT prototypes (CT01709E & F) described in R8816.

10/10/89 HRRC APPROVED R8933 (T. A. Perfetti) for SED QDA or diagnostic testing after "warm-up" sessions with panelists. Focus group testing approved with no pre- or post-placement. Two-pack monadic testing not approved. Products contained experimental G7 sheets with either LA, nic:,La3, malic acid (MA), or nic:Ma2, at 25% by wt inclusion in cigarettes. 01/23/90 HRRC APPROVED R9002 (J. H. Robinson) to perform plasma nicotine study of 4, 50% air-diluted GTX prototypes described in R8933. 02/27/90 HRRC APPROVED R9006 (T. A. Perfetti) to perform focus groups with no prior placement or other low-consumption SED tests with pdts containing up to 10,000 ppm Ca or Na levulinates. Approval for 2-pack tests of similar pdts deferred pending results of plasma nicotine tests. Data on thermal stability of Ca & Na salts requested (rec'd & passed on to Scientific Affairs) Need for 28-day inhalation test prior to market placement noted. Scientific Affairs ok'd 1-cigt exposure in focus groups w/ no pre-or post-placement. Ames tests showed Na- & Ca-levulinates to be neither mutagenic nor toxic. Condensate mutagenicity not affected by salts. Complete smoke data on all prototypes 10/23/90 HRRC DEFERRED APPROVAL R9035 (M. F. Dube) to perform PGT test (2- pack monadic) in 300 smokers until additional data available. Specifically, LD50 of nic:La, plasma nic, test of multiple, consecutive smokings, "tar" & nic data from actual mail-out -products. Committee to meet 11/15/90 to review data. 10/31/90 HRRC APPROVED R9038 (J. H. Robinson) In "Study I" 12 volunteers to smoke 4 each of products described by Dube (R9035) at 1/2 hr intervals. 6 to smoke Product C (5.1 tar, 0.64 mg nic, 2.32% LA3:Nicl. 6 to smoke Product E (5.3 mg tar, 0.83 mg nic, 3.27% LA1:Nic1). In "Study 2", ?st test group (3-5) employee volunteers provide AM & PM blood samples for 3 days. Smoke ad lib reg brand on day 1; day 2&3 smoke ad lib from up to 2 packs (total) Product C. 2nd test group smokes ad lib from up to 2 packs of "C" 7 only fill out questionnaires, re physiological and sensory responses. 10/31/90 HRRC APPROVED R9038b, in which addition of 24-hr urine sampling