ENDS Toxicity / Carcinogenic: Difference between revisions

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'''Studies, Surveys, Papers, and Case Studies'''

*Sometimes it's necessary to view the PDF version to access the full study.

*Blood lead levels, and urinary cadmium, barium, and antimony levels were similar between participants who used e-cigarettes and participants who did not.

*However, participants with a smoking history were more likely to have higher blood lead and urinary cadmium than participants who neither used e-cigarettes nor cigarettes.

*We first report that HTP (Heated Tobacco Product) delivers slightly less nicotine and emits much lower amounts of carbonyl and PAH compounds than tobacco cigarettes.

*However, HTP emissions still contain carcinogenic compounds (e.g. formaldehyde, acetaldehyde and benzo[a]pyrene) and the amounts of carbonyls and PAHs in HTP aerosols are higher than in e-cig vapours.

*The results of this study concorded with evidence that complete switching from combustible cigarettes to vapor products may reduce exposure to key carcinogens and other toxicants known to be associated with tobacco-related diseases.  

*[https://scholar.google.com/scholar_url?url=https://academic.oup.com/ntr/article-pdf/22/8/1285/33503504/ntz206.pdf&hl=en&sa=T&oi=ucasa&ct=ufr&ei=7UfSX7_HNY7gygS59oeICg&scisig=AAGBfm2cHOs4tggW6_ESThVFWjYP98IvZw PDF Version]

*Many consumers are misinformed about the harms of [[Special:MyLanguage/Abbreviations|electronic nicotine delivery systems (ENDS)]].

*Many adults believe, erroneously, that ENDS are as harmful as combustible tobacco products, and the level of public understanding has deteriorated over time. In 2012, only11.5% of respondents to a national survey held this view. By 2015, 35.7% of respondents mistakenly believed that the harm associated with electronic cigarettes (e-cigarettes) was “about the same” as that of smoking conventional cigarettes.

*The IQOS heated tobacco product emits substantially lower levels of carbonyls than a commercial tobacco cigarette but higher levels than an e-cigarette.  

*[https://sci-hub.se/10.1111/add.14365 PDF Version]

*Of the 51 toxicants tested, eight were detected in the e-cigarette aerosols but at substantially lower levels than reported in cigarette smoke.

*Link above to the PDF form of the information presented at: 1st Scientific Summit, Tobacco Harm Reduction, Kallithea, Greece, June 2018

*In this study, we have demonstrated that no clinically relevant, product-related safety findings were observed for smokers of Combustible Cigarettes (CC) switching to an [[Special:MyLanguage/Abbreviations|Electronic Vapor Product (EVP)]] for 12 weeks under real-life settings. Adverse Effects (AEs) reported by subjects switching to the EVP occurred primarily within the first week after switching, and only 1.3% of all AEs reported were considered to be almost definitely related to the product. Up to a third of all reported AEs in the EVP group were related to nicotine withdrawal symptoms, which were observed to decrease after the first two weeks from product switch. EVP use was associated with significant decreases in exposure to nicotine and other chemicals such as benzene and acrolein, typically found in CC smoke. Changes were also observed in the level of WBC, haemoglobin, RBC and LDL cholesterol, which although minor, were consistent with those observed after smoking cessation. The data presented in this study shows the potential that EVPs may offer to smokers looking for an alternative to CCs.

*[https://sci-hub.se/10.1016/j.jaerosci.2017.10.006 PDF Version]

*In this population-based cohort study of 5105 participants, current exclusive e-cigarette users had greater concentrations of biomarkers of nicotine, tobacco-specific nitrosamines, volatile organic compounds, and metals compared with never tobacco users. However, these concentrations were lower than those observed in current exclusive cigarette smokers and dual users of both products.

*[https://documentcloud.adobe.com/link/track?uri=urn%3Aaaid%3Ascds%3AUS%3A0923e7cd-7d55-45fc-923e-4ad06343a73e#pageNum=1 PDF Version]

*There is conclusive evidence that completely substituting e-cigarettes for combustible tobacco cigarettes reduces users’ exposure to numerous toxicants and carcinogens present in combustible tobacco cigarettes.

*There is substantial evidence that except for nicotine, under typical conditions of use, exposure to potentially toxic substances from e-cigarettes is significantly lower compared with combustible tobacco cigarettes.

*The risks from benzene will be lower from e-cigarettes than from conventional cigarettes.

*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342216/pdf/pone.0173055.pdf PDF Version]

*Results from this study suggest that e‐cigarettes may have reduced tumor promoter activity compared to conventional cigarettes and therefore may provide a safer alternative to cigarettes.

*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435921/pdf/EM-58-190.pdf PDF Version]

*In realistic conditions, formaldehyde in e-cigarettes is lower than cigarette smoke

*The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided.

*While not harmless, electronic cigarettes (e-cigarettes) have demonstrated a much more favourable (favorable) toxicological profile than combustible cigarettes—the worldwide leading cause of preventable death. Average eCO levels (ppm) were significantly higher in smokers than in e-cigarette users. Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant.

*[https://tobaccocontrol.bmj.com/content/tobaccocontrol/26/e1/e23.full.pdf PDF Version]

*In general, the findings of this study suggest that the concentrations of most trace metals extracted from cigarette smoke exceed the concentrations of trace metals extracted from ECIG-generated aerosol.  

*Only Ni in the ECIG-generated aerosol was higher than control (smoke). The most probable source of Ni in this aerosol is the core assembly.

*Former smokers with long-term e-cigarette–only or NRT-only use may obtain roughly similar levels of nicotine compared with smokers of combustible cigarettes only, but results varied. Long-term NRT-only and e-cigarette–only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes.

*[https://sci-hub.se/10.7326/M16-1107 PDF Version]

*Most e-cigarette analyses indicate cancer potencies <1% that of tobacco smoke and <10% that of a heat-not-burn prototype, although a minority of analyses indicate higher potencies.

*Optimal combinations of device settings, liquid formulation and vaping behaviour normally result in e-cigarette emissions with much less carcinogenic potency than tobacco smoke.

   

*Provision of the nicotine that smokers are addicted to without the harmful components of tobacco smoke can prevent most of the harm from smoking.

*E-cigarettes are marketed as consumer products and are proving much more popular than NRT as a substitute and competitor for tobacco cigarettes.

*In this study, we have demonstrated that no clinically relevant, product-related safety findings were observed for smokers of Combustible Cigarettes (CCs) switching to an [[Special:MyLanguage/Abbreviations|Electronic Vapor Product (EVP)]] for 12 weeks under real-life settings. [[Special:MyLanguage/Abbreviations|AEs]] reported by subjects switching to the EVP occurred primarily within the first week after switching, and only 1.3% of all AEs reported were considered to be almost definitely related to the product. Up to a third of all reported AEs in the EVP group were related to nicotine withdrawal symptoms, which were observed to decrease after the first two weeks from product switch. EVP use was associated with significant decreases in exposure to nicotine and other chemicals such as benzene and acrolein, typically found in CC smoke. Changes were also observed in the level of WBC, haemoglobin, RBC and LDL cholesterol, which although minor, were consistent with those observed after smoking cessation. The data presented in this study shows the potential that EVPs may offer to smokers looking for an alternative to CCs.

*[https://sci-hub.se/10.1016/j.yrtph.2016.10.003 PDF Version]

   

*After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced.

*[https://sci-hub.se/10.1093/ntr/ntw160 PDF Version]

   

*Smokers using [[Special:MyLanguage/Abbreviations|EC]]s over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, [[Special:MyLanguage/Abbreviations|NNAL]], and two out of eight measured [[Special:MyLanguage/Abbreviations|VOC]] metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.

*[https://sci-hub.se/10.1093/ntr/ntw333 PDF Version]

*Subjects switching to e-cigarettes had significantly lower levels (29 %–95 %) of urinary [[Special:MyLanguage/Abbreviations|BoE]]s after 5 days. Nicotine equivalents declined by 25 %–40 %.  

*Dual users who substituted half of their self-reported daily cigarette consumption with e-cigarettes experienced 7 %–38 % reductions, but had increases (1 %–20 %) in nicotine equivalents.  

*In the presence and absence of metabolic activation, e-cigarette [[Special:MyLanguage/Abbreviations|ACM]] and aerosol were deemed non-mutagenic in tester strains TA98 and TA100, under the test conditions described previously, despite clear positive control responses. Conversely, 3R4F cigarette smoke TPM and freshly generated whole smoke were clearly positive.  

*In the case of freshly generated cigarette smoke, a positive response in both strains was observed within 24 min, whereas e-cigarette aerosols remained negative up to 3 h.

*Under the conditions tested, Vype ePen e-cigarette aerosol was significantly less cytotoxic than reference 3R4F cigarette smoke.

*[https://sci-hub.se/10.1080/15376516.2016.1217112 PDF Version]

   

*Despite being tested with a more intense puffing regime, e-cigarette aerosol showed no acute cytotoxicity in this study when compared with traditional 3R4F reference cigarette smoke.

*Under the study conditions cigarette smoke demonstrated a dose-dependent response that resulted in near-complete cell death after a 6 h exposure period. In contrast, e-cigarette aerosol showed no decrease in tissue viability following a 6 h exposure, despite appropriate positive control responses. Furthermore, cytotoxicity appears to be unaffected by different e-cigarette formulations as tested in this study.

   

*No significant contribution of tested HPHC classes was found for the e-cigarettes.

*[https://sci-hub.se/10.1016/j.yrtph.2014.10.010 PDF Version]

   

*Existing evidence indicates that E-cigarette (EC) use is by far a less harmful alternative to smoking. There is no tobacco and no combustion involved in EC use; therefore, regular vapers may avoid several harmful toxic chemicals that are typically present in the smoke of tobacco cigarettes. Indeed, some toxic chemicals are released in the EC vapor as well, but their levels are substantially lower compared with tobacco smoke, and in some cases (such as nitrosamines) are comparable with the amounts found in pharmaceutical nicotine products. Surveys, clinical, chemistry and toxicology data have often been mispresented or misinterpreted by health authorities and tobacco regulators, in such a way that the potential for harmful consequences of EC use has been largely exaggerated. It is obvious that some residual risk associated with EC use may be present, but this is probably trivial compared with the devastating consequences of smoking. Moreover, ECs are recommended to smokers or former smokers only, as a substitute for conventional cigarettes or to prevent smoking relapse; thus, any risk should be estimated relative to the risk of continuing or relapsing back to smoking and the low efficacy of currently approved medications for smoking cessation should be taken into consideration….

*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110871/pdf/10.1177_2042098614524430.pdf PDF Version]

*The levels of potentially toxic compounds in e-cigarette vapor is from 9 to 450-fold lower than those in the smoke from conventional cigarettes, and in many cases comparable to the trace amounts present in pharmaceutical preparation (Note: Reference product was a medicinal nicotine inhaler.). Our findings support the idea that substituting tobacco cigarettes with electronic cigarettes may substantially reduce exposure to tobacco-specific toxicants.

*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154473/pdf/nihms-624084.pdf PDF Version]

    

*With respect to the compounds analyzed here, e-cigarettes have a more favorable toxicity profile than tobacco cigarettes.

*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481723/pdf/ntu218.pdf PDF Version]

   

*This study indicates that EC vapor is significantly less cytotoxic compared to tobacco CS.

*[https://sci-hub.se/10.3109/08958378.2013.793439 PDF Version]

*[[Special:MyLanguage/Abbreviations|EC]] emissions contain trace levels of metals. For almost all metals, unrealistically high levels of liquid need to be consumed in order for total daily exposure to exceed established limits.

*[https://sci-hub.se/10.1080/08958378.2018.1523262 PDF Version]

*Most potential impurities or degradation products were not detectable.

*Impurities or degradation products found were below occupational exposure limits

*[[Special:MyLanguage/Abbreviations|Threshold Limit Values (TLVs)]], were conducted under “worst case” assumptions about both chemical content of aerosol and liquids as well as behavior of vapers.

*There was no evidence of potential for exposures of e-cigarette users to contaminants that are associated with risk to health at a level that would warrant attention if it were an involuntary workplace exposures.

*From our review of the literature and bearing in mind the long experience with theatrical mists, the short-term toxicity can be considered to be very low

*Many smokers see the e-cigarette as a good way to quit smoking

*Our results clearly show a lower toxicity of e-liquids, including flavoured e-liquids, when compared to CSC (cigarette smoke condensate). Typically, more than 100 times higher concentrations of CFs (Base liquids, with or without nicotine, and commercial, flavoured, nicotine-containing e-liquids) are required to elicit the same response as those observed for 3R4F CSC in specific endpoints.

*Flavours play a critical role in attracting, and retaining smokers to e-cigarettes.

*The vast majority of flavouring (flavoring) compounds in e-cigarette liquids as reported in a recent study were present at levels far lower than needed to classify them as toxic.  

*[https://harmreductionjournal.biomedcentral.com/track/pdf/10.1186/s12954-019-0318-2.pdf PDF Version]

*Aldehyde emissions from all flavoured liquids were 79–99.8% lower than smoking and lower than commonly measured indoor levels and occupational and indoor safety limits.

*[https://sci-hub.se/10.1016/j.fct.2018.02.059 PDF Version]

*In vitro and Animal

*Individual flavours or groups of flavours were added to the tobacco rod and the resultant smoke was analysed for priority smoke constituents and tested in several in vitro tests as well as 90-day rat inhalation studies. In general, addition of the flavours had no effect on, or reduced the levels of most of the measured smoke constituents.”

*Among established, every day, exclusive tobacco product users, the geometric mean urinary NNAL concentration was  

#highest for smokeless tobacco users (993.3 ng/g creatinine),  

*Animal Study

*Standard toxicological endpoints were complemented with systems toxicological analyses using transcriptomics, proteomics, and lipidomics of lung tissue, liver tissue, and serum. Both standard and systems toxicology endpoints demonstrated very limited biological effects of PG/VG aerosol with no signs of toxicity Systems toxicology analyses detected biological effects of nicotine exposure, which included up-regulation of the xenobiotic-metabolizing enzymes Cyp1a1 and Fmo3 in the lung and metabolic effects, likely interlinked with a generalized stress response to nicotine present in the exposure aerosols

*Tests performed by the FDA have shown that e-cigarettes have similar nicotine levels and trace contaminants as NRT products.  

*Propylene glycol (PG) is generally recognized as safe by oral, dermal or inhalation routes and has been a common ingredient in all American made tobacco cigarettes for seven decades.”

*Current state of knowledge about chemistry of liquids and aerosols associated with electronic cigarettes indicates that there is no evidence that vaping produces inhalable exposures to contaminants of the aerosol that would warrant health concerns by the standards that are used to ensure safety of workplaces

*[https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/1471-2458-14-18.pdf PDF Version]

*The nicotine content of electronic cigarette refill bottles is close to what is stated on the label. Impurities are detectable in some brands above the level set for nicotine products in the European Pharmacopoeia, but below the level where they would be likely to cause harm.

*[https://sci-hub.st/10.1111/add.12235 PDF Version]

*Upon reviewing the available toxicity information, the Agency has concluded that there are no endpoints of concern for oral, dermal, or inhalation exposure to propylene glycol. This conclusion is based on the results of toxicity testing of propylene glycol in which dose levels near or above testing limits (as established in the [https://www.epa.gov/test-guidelines-pesticides-and-toxic-substances/series-870-health-effects-test-guidelines OPPTS 870 series harmonized test guidelines]) were employed in experimental animal studies and no significant toxicity observed.

*A review of the available data has shown propylene glycol to be negative for carcinogenicity in studies conducted up to the testing limit doses established by the Agency; therefore, no further carcinogenic analysis is required.

*Topic

*Year (list new to old) Name of Study (In link format to the study)

*Click on the category link below for more studies by topic on ENDS and Nicotine.

[[Category:Studies, Surveys, and Papers]]

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