Toxicity data for all used additives; includes codes.
Proposes continuation of Project B412. Notes recent findings indicate additives increase nicotine migration and previous work shows malic acid added to cigarette paper increases nicotine in peripheral smoke. States project will optimize additives for increased nicotine delivery and controlling smoke pH will result in "satisfactory taste and impact". Suggests additional nicotine chemistry mechanisms studied may yield results for publication. Notes the project objectives: "to optimize migration of nicotine to the periphery of the cigarette,...improve the delivery to mainstream smoke,...understand the mechanisms of nicotine reactions with selected salts and acids." Submits a time-line and man-hours required for technical analysis.
Examines the carcinogenicity of oxolamine citrate and contrasts with the non-carcinogenicity of PMO. Bladder carcinogenesis of oxolamine in animals is identified as related to the diethylaminoethyl group and not the 3-phenyl-1,2,4-oxadiazoyl moiety. Suggests that diethylamine, a urinary metabolite of oxolamine, may be nitrosated in vivo to the carcinogen N-nitrosodiethylamine. Rejects PMO as the source of carcinogenicity.
Details percentage of free and bound nicotine, and smoke pH for Kent III and experimental low-tar cigarettes.
Reports results of CONAP project to enrich reconstituted leaf [RL] with nicotine and study the migration of nicotine from cut tobacco to RL. Lists experimental conditions including: spraying RL with ammonia which was then mixed with cigarette tobacco, use of phosphoric acid and monoammonia phosphate, evaluation of moisture content on nicotine migration, nicotine migration under storage conditions, and elucidating the chemical properties using phosphoric acid treated filter papers. Presents results of nicotine transfer of Kent Gold Light Blend and nicotine transfer properties using various additives. Lists migration of nicotine during aging, leaf analysis of various tobacco grades including 7-74, HL-74, SMEM-75, VLO-75, MX-70, MIIX-70, MIIX-71 and reports leaf pH, %Nicotine, %Nitrogen, % Total Volatile Bases, % Nicotine migration to filter paper and correlates leaf pH, Nicotine, Nitrogen and Total Volatile Bases to nicotine transfer. Recommends further studies to include: quantitation of nicotine migration, migration of nicotine to RL, "migration of nicotine to Cytrel or similar materials", characterizing compounds that co-migrate with nicotine and the migration of nicotine during storage.
Proposes development of methods which distinguish the major bound and free organic acids in tobacco. Indicates organic acids and leaf nicotine may play a role in tobacco off-taste, strength and character. Suggests increased research in this area may provide a means to improve low grade/off-shore burley tobacco smoke qualities.
Reports results of nicotine migration studies "as induced by the presence of malic or tartaric acid." Indicates "impregnation of cigarette paper with acid can cause migration of nicotine to the periphery" causing elevated nicotine delivery into mainstream smoke." Tests levels of nicotine migration and constituent yields based on tobacco and paper types, and other factors.
Describes laboratory studies in which "substantial increases in smoke pH and smoke impact [were] obtained by the application of certain calcium and potassium compounds" that naturally occur in tobacco. Proposes proper application of compounds "could be useful for improving cigarette impact and thus, consumer satisfaction." Notes that supplementation of naturally occurring compounds to increase alkalinity in cigarettes would eliminate need for "extensive toxicity studies."
States that the data on total amino acid content in tobacco blends was needed for two projects (E-134 and C-133). Reports that Analytical Biochemistry Labs determined the amino acid content by an analysis of the hydrolysate. Warns that with this method tryptophan is destroyed and possible reduction in amino acids by the slow reaction with carbonyl compounds during hydrolysis can occur. Presents levels of amino acids from the data broken down by cigarette brand; Kent, Marlboro, Vantage, True, and Zack. Includes an analysis for amino acids in burley, Turkish and flue-cured tobacco. States that high aspantic means high burley, high proline means high flue-cured, and high glutamine means high Turkish tobacco. Gives a general ratio of tobacco blend: if burley is increased, both flue-cured and Turkish must go down, unless flue-cured is increased dramatically relative to the Turkish. Finds a contradiction for Vantage and Marlboro brands. States that in both brands the asparlic acid and the proline levels are high, but in Vantage the glutamine is also high. Declares that these results are impossible unless Marlboro and Vantage are adding nitrogen containing additives to their tobacco.
Investigates this premise by subtracting protein nitrogen
and nicotine nitrogen from total nitrogen. Finds that nitrogen compounds are being added to Marlboro and Vantage, but not to Kent, True or Zack. Reveals that a patent search confirms that Philip Morris uses ammonium phosphate and Reynolds uses a Schiff base. Identifies a Schiff base as an aldehyde combined with a base such as ammonia. Anticipates the need to analyze tobaccos for Schiff bases, and surmises that liquid chromatography would be the most likely method to use.
Outlines the current status of the Continuation of Nicotine Augmentation Project [CONAP], says "development of flavorful, enjoyable and physiologically satisfying cigarettes which will deliver lower tar and reduced amounts of gas phase components, yet deliver nearly comparable quantities of nicotine" is crucial, requires a multi-faceted approach and lists personnel assigned to each project. States a thorough literature search will avoid duplication of efforts, notes the commercial sourcing of pure nicotine is integral as "One obvious means to increase the nicotine content...of low tar delivery cigarettes is to add nicotine to the tobacco." and lists internal nicotine sources including: waste tobacco, drier exhaust, and processing-transfer. States nicotine can be applied to total blend or components, that less than 1% nicotine alkaloid [as tartarate] provides impact, and additions will be restricted to reconstituted leaf [RL] or puffed tobacco. States further research of chemical treatment with ammonia and other materials will continue with the objective to increase free nicotine content of smoke, air dilution cigarette construction indicates tar/nicotine ratios can be manipulated and smoke and leaf pH studies remain current. Indicates a focus on reduction of nicotine pyrolysis to increase nicotine delivery, filter materials selective for nicotine passage, and reducing volatile humectants to increase flavor and nicotine in delivered tar. Says plasticizers increase the weight of tar and a less volatile plasticizer be explored. Says literature searches for the physiological effects of nicotine will continue for new information, that nicotine/tar ratios of competitive brands be monitored for elevations beyond the norm, and further exploration of novel flavor supplements may make low tar cigarettes acceptable. States additional studies using nicotine salts for impact or physiological effects be pursued, safety rules for nicotine handling be defined and notes the cooperative efforts of Research and Product Development are required to meet the immediate and long range Marketing Department objectives.
Reports a simple extraction method for the simultaneous measurement of nicotine and menthol. Says this method is used to study the effects of air dilution on puff-by-puff deliveries of nicotine and menthol. Finds increased air dilution enriches the nicotine content of tar more than menthol and this procedure is useful for analyzing cigarette filler.
Proposes continuation of grant to study the effects of nicotine, metabolites and /or alkaloids on the Central Nervous System [CNS] of animals and humans. Indicates this is an important area of research and submits progress report. Reports behavioral and EEG changes in cats at the 5-10 microgm/kg of nicotine doseage and proposes further studies of nicotine and related alkaloids on the limbic, hypothalamic and cerebral cortex before and after the use of blocking drugs be used to correlate them with behavior. Says nicotine alkaloids in tobacco smoke and metabolites of nicotine including cotinine need further study and human studies will include normal human and selected psychiatric patients. Indicates continued studies on the effects of nicotine and related alkaloids on learning in animals will be employed and remarks "These studies have not been pursued sufficiently and require the attention of a full time technician."
Memo tells of Lorillard R&D efforts to find PMO analogs that could be added to cigarettes without adversely affecting taste. The PMO analogs were important because they reverse ciliastasis (paralysis of cilia which clean the respiratory tract). Experiments were done on chicken trachea tissue. 21 analogs were prepared and they were observed to have less intense and less objectionable odors and taste than PMO. They sought analogs that would be "without undesirable physiological effects such as bronchodilation." Research was done with a eye towards potentially patententing the discovered substances.