Evaluation of the potential effects of ingredients added to cigarettes. Part 4: subchronic inhalation toxicity

Vanscheeuwijck, Patrick; Teredesai, A.; Terpstra, Piter; Verbeeck, J.; Kühl, Peter; Gerstenberg, Birgit; Gebel, Stephan; Carmines, E.L.

doi:10.1016/s0278-6915(01)00089-8

Cited by 107 publications

(85 citation statements)

References 30 publications

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“…The results and conclusions were consistent with those from other cigarette additive studies and with human epidemiological evidence indicating that smoke from cigarettes with additives was no more hazardous for health than smoke from additive free cigarettes (238). In their reply, WERTZ et al (235) stated that OLDHAM and MCKINNEY sidestepped the most important points of critique of the studies by CARMINES and colleagues (229)(230)(231)(232), and repeated their arguments without presenting new facts.…”

Section: Comprehensive Experimental Studiessupporting

confidence: 73%

“…• CARMINES (229), RUSTEMEIER et al (230), ROEMER et al (231) and VANSCHEEUWIJCK et al (232) In 2002, CARMINES (229) described a testing program designed to evaluate the potential effects of 333 commonly used additives -as mixtures -on selected chemical and biological endpoints in cigarette mainstream smoke. The experimental cigarettes were made of a typical commercial U.S. tobacco blend.…”

Section: Comprehensive Experimental Studiesmentioning

confidence: 99%

“…Between 7% and 15% of the tobacco was replaced by the additive mixtures in the six different experimental cigarettes. The purpose of the study was the determination -and publication in separate papers -of the effects of additives on 51 selected mainstream smoke constituents (230), on in vitro toxicity, assessed in the Ames Salmonella reverse mutagenicity test and the mouse embryo cell cytotoxicity (neutral red uptake) assay (231), and in 90-day nose-only smoke inhalation studies in rats (232). The results of mainstream smoke analysis were presented comprehensively in a table on a per cigarette basis.…”

Section: Comprehensive Experimental Studiesmentioning

confidence: 99%

“…(235). They pointed out that the approach and methods used (229)(230)(231)(232) were based on sound toxicological principles and guidelines. The testing program was developed by adapting ways of toxicological evaluation by the U.S. FOOD AND DRUG ADMINISTRATION for food additives (236) and proposed by the CONSUMER PRODUCT SAFETY COMMISSION for cigarettes (237).…”

Section: Comprehensive Experimental Studiesmentioning

confidence: 99%

“…Mainstream smoke of the same cigarettes as used in the study of ROEMER et al (231) was tested in a subchronic 90-day nose-only inhalation study in rats by VANSCHEEUWIJCK et al (232). An increase of mainstream smoke toxicity due to the use of 1,2-propylene glycol was not seen.…”

Section: 2-propylene Glycolmentioning

confidence: 99%

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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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Section: Comprehensive Experimental Studiessupporting

confidence: 73%

Section: Comprehensive Experimental Studiesmentioning

confidence: 99%

Section: Comprehensive Experimental Studiesmentioning

confidence: 99%

Section: Comprehensive Experimental Studiesmentioning

confidence: 99%

Section: 2-propylene Glycolmentioning

confidence: 99%

See 3 more Smart Citations

Influence of Additives on Cigarette Related Health Risks

Klus¹,

Scherer²,

Müller

2012

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

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Impact of whole‐body versus nose‐only inhalation exposure systems on systemic, respiratory, and cardiovascular endpoints in a 2‐month cigarette smoke exposure study in the ApoE^−/− mouse model

Kogel

Wong

Szostak

et al. 2021

J of Applied Toxicology

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Cigarette smoking is one major modifiable risk factor in the development and progression of chronic obstructive pulmonary disease and cardiovascular disease. To characterize and compare cigarette smoke (CS)‐induced disease endpoints after exposure in either whole‐body (WB) or nose‐only (NO) exposure systems, we exposed apolipoprotein E‐deficient mice to filtered air (Sham) or to the same total particulate matter (TPM) concentration of mainstream smoke from 3R4F reference cigarettes in NO or WB exposure chambers (EC) for 2 months. At matching TPM concentrations, we observed similar concentrations of carbon monoxide, acetaldehyde, and acrolein, but higher concentrations of nicotine and formaldehyde in NOEC than in WBEC. In both exposure systems, CS exposure led to the expected adaptive changes in nasal epithelia, altered lung function, lung inflammation, and pronounced changes in the nasal epithelial transcriptome and lung proteome. Exposure in the NOEC caused generally more severe histopathological changes in the nasal epithelia and a higher stress response as indicated by body weight decrease and lower blood lymphocyte counts compared with WB exposed mice. Erythropoiesis, and increases in total plasma triglyceride levels and atherosclerotic plaque area were observed only in CS‐exposed mice in the WBEC group but not in the NOEC group. Although the composition of CS in the breathing zone is not completely comparable in the two exposure systems, the CS‐induced respiratory disease endpoints were largely confirmed in both systems, with a higher magnitude of severity after NO exposure. CS‐accelerated atherosclerosis and other pro‐atherosclerotic factors were only significant in WBEC.

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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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Evaluation of the potential effects of ingredients added to cigarettes. Part 4: subchronic inhalation toxicity

Cited by 107 publications

References 30 publications

Influence of Additives on Cigarette Related Health Risks

Influence of Additives on Cigarette Related Health Risks

Impact of whole‐body versus nose‐only inhalation exposure systems on systemic, respiratory, and cardiovascular endpoints in a 2‐month cigarette smoke exposure study in the ApoE^−/− mouse model

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

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Evaluation of the potential effects of ingredients added to cigarettes. Part 4: subchronic inhalation toxicity

Cited by 107 publications

References 30 publications

Influence of Additives on Cigarette Related Health Risks

Influence of Additives on Cigarette Related Health Risks

Impact of whole‐body versus nose‐only inhalation exposure systems on systemic, respiratory, and cardiovascular endpoints in a 2‐month cigarette smoke exposure study in the ApoE−/− mouse model

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

Contact Info

Product

Resources

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Impact of whole‐body versus nose‐only inhalation exposure systems on systemic, respiratory, and cardiovascular endpoints in a 2‐month cigarette smoke exposure study in the ApoE^−/− mouse model