Tobacco Documents Online

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Lorillard located a supply in December of 1944 and decided to test sorbital for possible beneficial effects. (04365682/5684) Follow Up Studies Dr. Parmele reported the findings of the sorbitol studies in a June 6, 1945 letter as follows: tLl No difference in toxic or irritat- ing effects of smoke was found between gly- cerine or sorbitol cased cigarettes. Dr. Sperti's lab performed this test which measured tissue respiration. (2) Smoke analysis showed no e, tar, aldehydes, or pFI. changes in (3) Plasticity was not improved by sorbitol. (4) Sorbitol may have sma3.Il advantages as a humectant. (04365691-5692) The sorbitol tests done in 1945 were also deemed non- responsive. The biological tests were considered to focus on health effects irrelevant in Cipollone. The companion studies of chemical analysis, processability, and humectant properties were likewise associated with an irrelevant effect, i.e., throat irritation. O 8974949G ~

glycol was a less harmful hygroscopic agent were also to be investigated. Literature Review There was a literature review of tobacco research cover- ing the time period from 1920 to 1941 included in the July, 1942 report. Dr. Sperti wrote that all pertinent articles were studied and summarized. He forwarded summaries of about 70 articles. There were abstracts of chemical analyses, analytical methods, and physiological effects of smoke. Dr. Sperti did not specifi- cally address the issue of cigarettes and cancer. However, a few articles on that subject were abstracted by him. The following abstracts are the only ones relevant to the disease limitations in Cipollone. GLASSMAN, T. (1932). Studies on the concentration of the active carcinogenic principal in oils and fats. Krebsforsch, 37:Ii7, ."Extraction of tobacco ash or raw tar with water or ethyl alcohol yields a carcinogenic =e-P (iron phosphate) compound. Also in urine of cancer patients this compound united with formic acid can be obtained by treatment with Zda,zS. It is suggested that cancer depends on the failure to oxidize the normal catalyst in HCO4H-FeP(S~ completely so that the incompletely c~xidized product is farmad which is a tissue irritant." (04354740) *CAMPBELL, JA (1939). Carcinogenic the Z.` present in atmosphere and incident of primary lung tumor in mice. Brit. Cited by plaintiff's expert Jeffrey Harris 89749492 - 2 -

the throat and was deemed nonresponsive. Lorillard did research on some of these components after 196€1, but their concern was with the ciliotoxic effects. The later research was deemed responsive. Results The Philip Morris method of determining eye irritation was found unreliable. A new eye irritation technique was devel- oped. Philip Morris cigarettes were found as irritating as any other cigarettes using the new method. Cigarettes with no humec- tant proved least irritating. No useful conclusions were made concerning the role of the combustion products of humectants and smoke pH in eye irritation. (04354765/47fi$1 The combusion products of glycerine or sorbitol gave no depression in tissue respiration, while the products of diethylene glycol gave a temporary depression. Depressi e respira- tion was greater for Philip Morris than for Camel. Sodium Bicar- a Studies on smoke pH produced unremarkable findings, but studies on humectants concluded that sorbitol was superior to glycerine or diethylene glycol. Dr. Sperti proposed a less irritating cigarette that employed sorbitol as the humectant and alkalinizing agents to raise the smoke pH and neutralize formic acid. (04354776) In 1942 it was noted that sorbitol was in short supply due to Tv~s1IZ. bonate additive lessened depression of tissue respi {04354769/4770} 89749495 - --s -

*ROFFO AH (1938). Cancer Produced by Hydrocarbons from Different Types of Tobacco. Bol. inst. med. exptl. estud. cancer j15s3447 "Distillation of tobacco leaves into: 3. 100-120 C an aqueous liquid, dark yellow, strongly alkaline containing CO, CC}2, NH , Mefl~i, [Ac{}H?;, acetates, pyridine, me?hyl pyrolline, and fufural. 2. After two hours 350 [degrees] CO, CQ2, (NH )2 Cfl3, Ac4H, acetates, succinic acid, stagcinates, fumaric acid, fumarates, citric acid and phenol acids, pyrrole." (04354756) Responsiveness It seems that some early investigators theorized a linkk between irritation and carcinogenicity. It does not appear that Dr. Parmele of Lorillard or Dr. Sperti made this connection. They seemed more interested in throat irritation as solely an acute effect of cigarette smoke. Following these guidelines, most if not all of the work done by Dr. Sperti was deemed non- responsive. A possible exception may be the chemical analyses of cigarette smoke performed by Dr. Sperti. Phenols, pyridine ses, acids, and aldehydes were found to be present in smoke. Likewise, carbon dioxide, carbon monoxide, and a trace of ammonia were detected. Formic acid and acetic acid were identified and noted to be irritating to the throat. The chemical analysis portion of the report comprised only two pages of the over 200 page report. This research was concerned with their effects on 83749494 - 4 -

Exptl. Path. 20:22. "Cigarette smoke, under ordinary circum- stances, gives rise to a tarry matter which may occasionally produce hyperplasia and can- cer of the skin after prolonged application. It seems that the carbon in tobacco smoke counteracts the cancer-producing substances, and inorganic constituents aid the cancer- producing substances. The tarry matter frem tarred roads seems to be most potent, perhaps the dust (Si': and Fe) aid the effect of tar; this work was done with mice. K (04354742) *MCNALLY WD (1932). "The Tar in Cigarette Smoke and its Possible Effect" Am. J. Cancer 16:1502 "The irritants found in tobacco smoke which account for the 'cigarette cough,' (the chronic bronchitis of the cigarette smoker, the leucoplakia in heavy smokers and the recorded increase of cancer of the lung) contain nicotine, phenols, pyridine bases, and ammonia. The temperature is not an im- portant factor unless the cigarette is burned to the last cm. Almost all of the tarry residue may be absolved or retained by the body; this is a definite risk." ( 04354'747) *ROFFO A (1939). Filters cc Smoking: the Narghile and Cotton as Filters. Bol. inst. med. exptl. estud. cancer (Buenos Aires) [14z226j "Ultraviolet absorption ct:rves of tobacco smoke tars are shown. Removal of appreciable amounts of carcinogenic substances is demon- strated by the use of a narghile with a cot- ton filter." (04354761) Cited by plaintiff's e.cpert Jeffrey Harris - 3 -

DR. SPERTI, RESEARCH CONDUCTED FROM 1941 TO 1945 FFOR LORILLARD Proposal and Objectives In September, 1941, M_r. Philip W. Lennen, of Lennen & Mitchell, Incorporated, New York City, an advertising agency for Lorillard, suggested to Dr. George Sperti, Director of the Insti- tutum Divi Thomae, that he undertake research on the improvement of cigarettes in the interest of Lennen & Mitchell. {p4354539} A comprehensive report of the research undertaken was submitted in July of 1942. The title of the report reads "Factors Con- tributing to the Harmful Properties of Cigarette Smoke." There is a subtitle which reads "Indications for a Possible New Type Cigarette." The problem to be investigated was more specifically defined as "[the production of] a cigarette which has less harm- ful effect on the throat than any other cigarette." (04354544) Three types of tests were considered. The first tests were chemi- ca3l and physicall analyses of the smoke and volatile materials drawn from a cigarette in the act of smoking. The second type of tests were designed to confirm or refute irritation tests per- e 4orris. Specifically, it was to be dete=-r.tined if the rabbit eye edema test was a reliable quantitative means of determining irritation. A third test was a new technique devel- oped in Dr. Sperti.'s laboratory. This test measured tissue res- ion. It was proposed to alter several variables to deter- mine if the a es could be made less harmful, that is, be made less irritating. The Philip Morris reports that diethylene 89749491