Comparative Inhalation Study in Rats, Using a Second Prototype of a Cigarette that Heats Rather than Burns Tobacco

Coggins, Christopher R. E.; Ayres, Paul H.; Mosberg, Arnold T.; Burger, Gary T.; Sagartz, John W.; Hayes, A. Wallace

doi:10.3109/08958378909145229

Cited by 33 publications

(18 citation statements)

References 13 publications

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“…Our studies (5,6,18,22) have supported the conclusion of Lewis (11,13) and Gopinath et al (8) that the epithelium lining the base of the epiglottis is the area of the laryngeal mucosa in laboratory rodents most susceptible to changes induced by inhaled irritants.…”

Section: Discussionsupporting

confidence: 88%

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Interspecies Variations in the Histology of Toxicologically Important Areas in the Larynges of CRL:CD Rats and Syrian Golden Hamsters*†

1993

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Specific regions in the rodent larynx exhibit cellular changes in response to inhaled xenobiotics. These regions include the base of the epiglottis, ventral pouch, and medial surfaces of the vocal processes of the arytenoid cartilages. There are interspecies differences among laboratory rodents in the microscopic anatomy of these sensitive areas of the laryngeal mucosa. In CRL:CD strain Sprague-Dawley rats, the mucosa covering the epiglottis differs from that of Syrian golden hamsters. The epithelium covering the base of the epiglottis is relatively thin in rats and is composed of a mixture of cell types, whereas in hamsters it is much thicker and is made up almost entirely of tall ciliated columnar cells. The cartilage supporting the ventral pouch in the larynges of hamsters is much more prominent than in rats and forms a distinct protrusion into the laryngeal lumen at the base of the epiglottis. The purpose of this paper is to describe and illustrate these and other subtle differences in rat and hamster laryngeal anatomy, which may be of toxicologic significance.

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Section: Discussionsupporting

confidence: 88%

“…As in the nose, the predilection of these sites for lesions in rodents is probably due to airflow characteristics and regional epithelial sensitivity (4,8,11,13 (5,6,22) or glycerol (18). Sources, housing, and necropsy procedures for the animals of these studies have been reported previously (5,6,18,22 …”

Section: Introductionmentioning

confidence: 99%

Interspecies Variations in the Histology of Toxicologically Important Areas in the Larynges of CRL:CD Rats and Syrian Golden Hamsters*†

1993

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“…For the highest dose level of each cigarette and for the sham-exposed group, a satellite group (10 male and 10 female rats) was kept without treatment for 42 days after inhalation. This period is deemed sufficiently long to investigate the reversibility of the findings typically seen in subchronic mainstream smoke inhalation studies (Coggins et al, 1989b).…”

Section: Experimental Experimental Designmentioning

confidence: 99%

“…Such designs, in which the burning tobacco as the energy source is replaced by a slowly and continuously smoldering carbon heat source, yield smoke aerosols composed primarily of water and glycerine. Subsequent designs again burned some tobacco (Coggins et al, 1989b), most likely to enhance taste.…”

Section: Introductionmentioning

confidence: 99%

Toxicological evaluation of an electrically heated cigarette. Part 4: Subchronic inhalation toxicology

Terpstra¹,

Teredesai

Vanscheeuwijck³

et al. 2003

J of Applied Toxicology

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The biological activity of mainstream smoke from an electrically heated cigarette (EHC) with controlled combustion and from the University of Kentucky Reference Cigarette 1R4F was determined in Sprague Dawley rats exposed nose-only for 90 days, 6 h a day, 7 days per week. For an equivalent response comparison between the two cigarette types, two doses were chosen for the EHC where the anticipated results were in the dynamic range of the 1R4F dose-response curve (four concentrations) for most end points. The number of cigarettes smoked per m(3) of diluted smoke resulted in total particulate matter concentrations of 40 and 90 microg l (-1) for the EHC and 40-170 microg l (-1) for the 1R4F. Biomonitoring indicated achievement of target doses. Mainstream smoke yields were lower for the EHC, with the exception of formaldehyde. No smoke-related mortality, remarkable in-life observations or abnormal gross pathological findings were observed. Smoke- and dose-related clinical pathology and organ weight changes included: increases in segmented neutrophils, some liver parameters and lung and adrenal weight relative to body weight; and decreases in lymphocytes, glucose concentration and spleen weight. Smoke-related histopathological findings in the respiratory tract included epithelial cell hyperplasia, squamous metaplasia, atrophy and accumulation of pigmented alveolar macrophages; they were mostly dose-dependent, more pronounced in the upper than lower respiratory tract and completely or partially reversed by 6 weeks post-inhalation. Qualitatively, the biological effects seen for the EHC and the 1R4F were comparable and similar to those observed in other mainstream smoke inhalation studies. Quantitatively, the biological activity of the EHC mainstream smoke was, on average, 65% lower than that of the 1R4F mainstream smoke on an equal cigarette basis and equivalent activity on an equal TPM basis.

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“…The comparative sister chromatid exchange assay with smoke condensate of the cigarettes used in (351) and (352) were absent or (primarily in the larynx) substantially reduced and completely reversible in the animals exposed to the smoke of the novel cigarette type. In an inhalation study of similar experimental design (360) with mentholated cigarettes of the traditional and the novel type, the response pattern observed after smoke exposure and the reversibility of lesions were the same as with the comparable non-mentholated test pieces (359). The addition of menthol did not influence the substantial difference in biological effects noted between the two types of cigarettes.…”

Section: Mentholmentioning

confidence: 81%

Influence of Additives on Cigarette Related Health Risks

Klus¹,

Scherer²,

Müller

2012

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

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Tobacco additives play an important role in the manufacturing and for the quality of tobacco products, particularly cigarettes and roll-your-own tobaccos. Attention is increasingly given to the potential effects of additives on consumer behavior and health. This review is intended to compile, collate and - to some degree - evaluate the wealth of pertinent scientific information available from the published literature and other special sources. At first, the reasons are set forth for the use of additives in cigarette manufacturing. In response to the growing controversy over the attractiveness and addictiveness of smoking, the clarification of terms and concepts is followed by a detailed discussion of two kinds of substances with particular relevance: Additives like ammonium compounds that are claimed to increase nicotine availability, and additives that are claimed to increase nicotine addictiveness.The composition and toxicity of mainstream smoke of cigarettes with and without additives are assessed in several respects. The potentials of pyrolysis studies are explored by looking at a number of key studies and some basic considerations regarding in vitro and in vivo toxicity testing are addressed. Five major literature reviews on additives published between 1994 and 2004, and the results of several comprehensive experimental studies covering a large range of additives, released between 2002 and 2012, are dealt with in detail. Single tobacco additives of particular importance (menthol, glycerol, 1,2-propylene glycol, sorbitol, sugars, cocoa, licorice, citric acid, triacetin, and ammonium compounds) are discussed in dedicated chapters, which are generally subdivided into special sections: Use and toxicological assessment; inclusion level in cigarettes, transfer and pyrolysis; attractiveness and addictiveness; effect on cigarette mainstream smoke composition; effect on cigarette mainstream smoke toxicity. Epidemiological findings and data obtained by the biomonitoring of smokers consuming cigarettes with and without additives are compiled and interpreted specifically for American blend cigarettes, Virginia cigarettes, “French” (dark) cigarettes and menthol cigarettes whereby the focus is on the effects of additives on smoking topography and potential health risks.Opinionated reviews were published in recent years that are compromised by arbitrary selection of sources and unbalanced views. Leaving those unconsidered, the aggregated scientific knowledge shows that tobacco additives have only occasional and limited effects on cigarette mainstream smoke composition, which are almost never reflected in the results of toxicological in vitro assays or in vivo studies. This supports the conclusion that tobacco additives are not likely to increase the known health risks of smoking. There is also no evidence for sustaining claims that certain additives increase nicotine availability or nicotine addictiveness.

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Comparative Inhalation Study in Rats, Using a Second Prototype of a Cigarette that Heats Rather than Burns Tobacco

Cited by 33 publications

References 13 publications

Interspecies Variations in the Histology of Toxicologically Important Areas in the Larynges of CRL:CD Rats and Syrian Golden Hamsters*†

Interspecies Variations in the Histology of Toxicologically Important Areas in the Larynges of CRL:CD Rats and Syrian Golden Hamsters*†

Toxicological evaluation of an electrically heated cigarette. Part 4: Subchronic inhalation toxicology

Influence of Additives on Cigarette Related Health Risks

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