Nonanimal toxicology testing approaches for traditional and deemed tobacco products in a complex regulatory environment: Limitations, possibilities, and future directions

Lauterstein, Dana; Savidge, Matthew; Chen, Yanling; Weil, Roxana; Yeager, R. Philip

doi:10.1016/j.tiv.2019.104684

Cited by 8 publications

(9 citation statements)

References 48 publications

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“…Different ENDS models are an issue with evidence from early studies. ENDS models are continuously evolving, so findings based on the first devices may not be applicable to current ones [ 60 ]. Five studies were conducted with the now discontinued “cig-a-like” models; they complicate the generalizability of study findings [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…First of all, cross-sectional studies cannot prove causation, because the temporal sequence of ENDS use and disease outcomes cannot be established. In vitro studies “still do not fully represent complex in vivo systems and may not directly translate to adverse effects relevant to disease outcomes” [ 60 ; see also 74 ]. Plus, the predictive capacity of in vitro testing is unknown [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

“…In vitro studies “still do not fully represent complex in vivo systems and may not directly translate to adverse effects relevant to disease outcomes” [ 60 ; see also 74 ]. Plus, the predictive capacity of in vitro testing is unknown [ 60 ]. In animal tests on ENDS (almost all with rats), exposures are performed with intra-tracheally or nasally administered liquids, or whole-body aerosol exposure, protocols that do not reflect human exposure levels [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

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Clinical testing of the cardiovascular effects of e-cigarette substitution for smoking: a living systematic review

et al. 2023

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Some persons who smoke have substituted e-cigarettes for tobacco cigarettes, either completely or partially. What effect does this have on cardiovascular functioning? We conducted a living systematic review on human clinical studies measuring the cardiovascular effects of e-cigarette substitution for smoking. The Scopus, PubMed, and CENTRAL Cochrane Library databases were searched on January 31 and April 29, 2021. Three secondary searches and a grey literature search were conducted. Included study designs were randomized controlled trials, quasi-experimental clinical trials, and cohort studies. Risk of bias and study quality were evaluated with the JBI Critical Appraisal tools and the Oxford Catalogue of Bias. The systematic review covered 25 studies comprising 1810 participants who smoked. Twenty studies were rated at high risk of bias, and five as some concerns. A tabular synthesis by direction of effect was conducted due to heterogeneity in the data. Nearly two-thirds of the test analyses indicated that e-cigarette use had no significance difference compared with tobacco cigarettes on heart rate, blood pressure, and in other cardiovascular tests. In two studies, participants with hypertension experienced a clinically relevant reduction in systolic blood pressure after 1 year of e-cigarette use. E-cigarette substitution incurs no additional cardiovascular risks, and some possible benefits may be obtained, but the evidence is of low to very low certainty. An update search on May 30, 2022 retrieved five studies that did not alter our conclusion.Registration PROSPERO #CRD42021239094.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Clinical testing of the cardiovascular effects of e-cigarette substitution for smoking: a living systematic review

et al. 2023

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“…Apesar dos avanços nestes ensaios, a extrapolação direta dos pontos finais do ensaio in vitro para os efeitos adversos relevantes para os sistemas in vivo é limitada uma vez que não temos disponíveis linhagens celulares adequadas que imite apropriadamente a resposta in vivo e os processos de ativação e inativação metabólica não são preservados integralmente nos ensaios in vitro (Lauterstein et al, 2020). Dessa maneira, os resultados adquiridos com testes in vitro ajudam a delinear os ensaios que deverão ser realizados in vivo além de direcionar quais substâncias serão testadas em tais ensaios (Benauer et al, 2005).…”

Section: Período De Observaçãounclassified

A importância dos ensaios de toxicidade para o desenvolvimento e o registro de fitoterápicos no Brasil

Silva

Furtado

Osório

et al. 2021

RSD

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Os estudos toxicológicos não-clínicos funcionam com um alicerce no processo de desenvolvimento de novos fármacos, visto que antecipam riscos e, portanto, reduzem a probabilidade de um novo fármaco interferir no metabolismo celular prejudicando a saúde do indivíduo além de não cumprir sua função farmacológica no organismo. Assim, considerando o potencial terapêutico das plantas medicinais, o presente trabalho tem como objetivo descrever a importância dos ensaios toxicológicos e os aspectos atuais concernentes ao registro de medicamentos fitoterápicos no Brasil. Para realização deste trabalho foram pesquisadas bases de dados científicas, tais como: Periódicos CAPES e Scielo, tendo o banco de dados sido complementado com artigos da legislação brasileira. Não houve restrição de busca quanto ao idioma ao ano de publicação dos materiais científicos, mas sim, quanto à relevância do seu conteúdo para o presente artigo. Dessa forma, observou-se que o papel regulador da ANVISA é fundamental para evitar que medicamentos ineficazes, tóxicos e de má qualidade alcancem o mercado e ocasionem problemas como intoxicações, interações com outros medicamentos, danos terapêuticos, ou até mesmo óbitos. Assim, por ser uma prática tradicional de saúde e já revelada em diversos estudos como de utilidade terapêutica por uma parcela significativa da população, torna-se interessante discutir a situação atual dos fitoterápicos e a seriedade que se deve ter no seu desenvolvimento principalmente diante dos ensaios toxicológicos não-clínicos uma vez que eles podem evitar problemas de saúde pública a curto e longo prazo.

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“…Thus, cigarette smoke is best assessed as “freshly” as possible or as it is generated [ 18 ]. Further, both TPM and GVP contain HPHCs that are known to contribute to toxic effects of cigarette smoke, and testing one type of sample alone is considered only a partial representation of cigarette smoke toxicity [ 19 ]. Additionally, cell cultures submerged in liquid often do not provide accurate dosimetry, which is an important component of risk assessment [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Cytotoxicity and Oxidative Stress of Whole Aerosol from Vuse Alto ENDS Products

Keyser,

Leverette,

Wertman

et al. 2024

Toxics

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Assessment of in vitro cytotoxicity is an important component of tobacco product toxicological evaluations. However, current methods of regulatory testing involve exposing monolayer cell cultures to various preparations of aerosols from cigarettes or other emerging products such as electronic nicotine delivery systems (ENDS), which are not representative of human exposure. In the present study, a whole aerosol (WA) system was used to expose lung epithelial cultures (2D and 3D) to determine the potential of six Vuse Alto ENDS products that varied in nicotine content (1.8%, 2.4%, and 5%) and flavors (Golden Tobacco, Rich Tobacco, Menthol, and Mixed Berry), along with a marketed ENDS and a marked cigarette comparator to induce cytotoxicity and oxidative stress. The WA from the Vuse Alto ENDS products was not cytotoxic in the NRU and MTT assays, nor did it activate the Nrf2 reporter gene, a marker of oxidative stress. In summary, Vuse Alto ENDS products did not induce cytotoxic or oxidative stress responses in the in vitro models. The WA exposures used in the 3D in vitro models described herein may be better suited than 2D models for the determination of cytotoxicity and other in vitro functional endpoints and represent alternative models for regulatory evaluation of tobacco products.

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Nonanimal toxicology testing approaches for traditional and deemed tobacco products in a complex regulatory environment: Limitations, possibilities, and future directions

Cited by 8 publications

References 48 publications

Clinical testing of the cardiovascular effects of e-cigarette substitution for smoking: a living systematic review

Clinical testing of the cardiovascular effects of e-cigarette substitution for smoking: a living systematic review

A importância dos ensaios de toxicidade para o desenvolvimento e o registro de fitoterápicos no Brasil

Evaluation of Cytotoxicity and Oxidative Stress of Whole Aerosol from Vuse Alto ENDS Products

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