Category: Science

  • CORESTA Concludes

    CORESTA Concludes

    Photos: BAT

    The Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) concluded its 2024 congress today.

    Hosted by BAT at the Edinburgh International Convention Centre, the congress opened Oct. 13 with 500 delegates, world-leading experts from member and nonmember organizations from more than 30 countries, attending. The theme was “Advancing Tobacco Harm Reduction Through Scientific Collaboration.”

    According to BAT, the event facilitated international dialogue on best practices in scientific research related to tobacco and nicotine alongside highlighting research findings and outcomes from CORESTA members.

    Danni Tower, group head of science and regulatory affairs at BAT, delivered the opening keynote speech, outlining the progress BAT has made in driving forward the tobacco harm reduction agenda. Tower called for more effective scientific collaboration in critical areas.

    All public health agencies, including WHO, should engage with CORESTA scientists to accelerate change.

    “The CORESTA Congress demonstrates the importance of collaboration amongst the entire scientific community to fully realize the public health opportunity of tobacco harm reduction,” said Tower in a statement. “We are proud to have hosted such an important event and strongly believe that positive global change is possible if all stakeholders recognize the potential of THR.

    “To achieve this, more open conversations like those we have had this week are needed across the scientific and regulatory landscape, which is why we have recently launched Omni—Forward Thinking for a Smokeless World—an open, evidence-based platform built on leading scientific research.”

    “Presentations at CORESTA demonstrated scientific advances underway in using new approaches to accelerate tobacco harm reduction,” said keynote speaker Derek Yach. “These extend from the use of genomics in agricultural sciences to the development of biomarkers in actual use studies and the application of AI tools to advance our knowledge of causes and effectiveness of interventions. All public health agencies, including WHO, should engage with CORESTA scientists to accelerate change.”

  • CoEHAR to Open Branch in Indonesia

    CoEHAR to Open Branch in Indonesia

    Photo: CoEhar

    The Center of Excellence for the acceleration of Harm Reduction (CoEHAR) at the University of Catania, Italy, signed a letter of intent with the Universitas Padjadjaran to create a new CoEHAR branch in Indonesia. The branch will serve as a regional center for research, outreach and education on smoking harm reduction in the Asia-Pacific region.

    According to statistics from the World Health Organization and other groups, Indonesia had nearly 80 million smokers aged 15 and older in 2022. This places the country third in the world in terms of the number of tobacco users. Conventional cigarette smoking remains the second-highest risk factor in Indonesia.

    “The research conducted by the CoEHAR team at the University of Catania is changing the world, contributing to the revolution of policies aimed at protecting public health in many countries,” said CoEHAR founder Riccardo Polosa in a statement. “Supporting the CoEHAR efforts in Indonesia is a great source of pride for us but also a promise of further commitment to change the fate of a country plagued by unhealthy habits and lifestyles.”

    “Low[-income] and middle-income countries in the Asian region represent a different and multifaceted field of investigation and activity,” said CoEHAR Director Giovanni Li Volti. “Our goal is to enhance research activities by developing joint projects that can fully utilize both the human and technological resources of all the universities and institutions involved, which will contribute to change and the exchange of knowledge and skills.”

    Previously, the universities had already agreed to promote joint research, mobility and training in the field of smoking harm reduction.

  • Inaccurate Disclosures Nicotine Analogs: Study

    Inaccurate Disclosures Nicotine Analogs: Study

    Photo: ryanking999

    Companies are inaccurately disclosing the ingredients in products containing nicotine analogs, according to researchers at Duke University and Yale University. Remarkably, in many instances, the levels measured were lower than those labeled on the packaging.

    Nicotine analogs are currently not subject to the U.S. Food and Drug Administration’s marketing authorization process and have not been extensively studied for their health effects. One chemical, known as 6-methyl nicotine, has been shown in rodent experiments to be far more potent than nicotine in targeting the brain’s nicotine receptors.

    The scientists analyzed a Spree Bar e-cigarette, which is listed as containing 5 percent 6-methyl nicotine. Study results showed the actual amount of the chemical was about 88 percent less than labeled. The e-cigarettes also included an artificial sweetener that is up to 13,000 times sweeter than table sugar, and an artificial coolant that mimics menthol’s effects.

    A second brand of e-cigarettes, marketed as Nixotine, Nixodine, Nixamide and Nic-Safe, contained a nicotine analog called nicotinamide, also at levels lower than the labels indicated, and combined with undisclosed amounts of 6-methyl nicotine. This brand did not include sweeteners or coolants.

    The researchers speculated that companies are using nicotine analogs to bypass health regulations covering vaping products.

    “These products appear to be designed to circumvent the laws and regulations in place to protect people—especially children—from the harmful effects of smoking and tobacco use,” said senior author Sven Eric Jordt in a statement. “We do not know what these chemicals do when they are heated and inhaled. These are questions that should be answered before we allow products on the market.”

  • Good Reads

    Good Reads

    Photo: Broughton

    The importance of literature reviews in support of tobacco harm reduction.

    By Dean Hatt

    Toxicology plays an important role in bringing next-generation products (NGPs) to market, ensuring they meet global regulatory requirements and contribute to the global body of evidence supporting tobacco harm reduction. Alongside analytical testing of the product’s aerosol, literature reviews are an important step in the toxicology human health assessment to build an understanding of the product’s performance, improve safety and ensure regulatory compliance. Here, Dean Hatt, senior toxicology consultant at scientific testing and consultancy specialist Broughton, shares insight into literature reviews for next-generation nicotine product toxicology.

    Toxicological tests help build an informed, scientifically justified understanding of the risk that NGPs present to health. This involves considering the nature of any hazards presented by an ingredient, exposure levels during normal usage, and the physical dose response, to build a risk characterization for the overall product.

    Toxicology assessments must be developed using a tailored approach to study design, data gathering, and risk assessment based on the product requirements and the proposed regulatory pathway.

    Importance of Literature Reviews

    Literature reviews are useful in two key areas of NGP development. Firstly, for hazard assessment, to gather data on specific toxicology endpoints for any chemical in the product and/or its aerosol. Hazard assessment is usually conducted relatively early in the product development process. By doing so, scientists can provide input into the sensitivity of analytical studies to establish if the identified components may be a health risk at the quantities identified.

    Literature reviews are also required as part of certain submissions, later in the product development process when completing the regulatory dossier. A thorough literature review is essential for manufacturers seeking approval via the marketing authorization application pathway to get their product approved as a nicotine-replacement therapy in the U.K. It is also necessary for those targeting premarket tobacco product application approval for consumer products in the U.S.

    Conducting a Literature Review

    A literature search for an NGP is a large body of work that can take several hundred hours to complete, depending on how wide the scope is. It encompasses assessing specific chemicals using authoritative sources or pre-agreed search terms and libraries.

    The literature search will typically involve hazard assessments for product-specific chemicals, where the scientist will look up various endpoints, e.g., carcinogenicity, genotoxicity, reproductive and developmental toxicity, irritation and sensitization from a number of sources to identify whether there is evidence that the chemical has toxicity associated with those endpoints.

    A CAS Registry Number is used as a unique identifier for a chemical, as some chemicals are referred to by different names or have different isomers. Menthol, for example, can take many forms: D menthol, L menthol, levomenthol and more.

    The researcher may also look for health-based guidance values, which demonstrate the level at which a chemical is deemed not to be of any concern. This is compared against the exposure concentration, which is derived from analytical data and estimated product consumption to quantify the risk.

    Wider Research

    When conducting wider research via a literature search as part of the regulatory application, the process will typically begin by agreeing on the search terms, such as “nicotine,” “toxicity” and “inhalation.” The researcher can then search agreed platforms, such as PubMed, PubChem and The British Library, to create a list, which often exceeds 2,000 references. The researcher will then prioritize these according to quality, recency and relevance to narrow the list down to the papers with the most appropriate information.

    If, during the literature search, a chemical is flagged for a specific toxicity, the researcher may recommend a more comprehensive assessment of that chemical, particularly if they have identified something the research team was not aware of.

    Further research may be required if there is a gap in the literature. It may be that the chemical has not been studied before or that it has not been included in any previous products due to its likely toxicity. There is also modeling (in silico) software available, such as Derek Nexus and Leadscope Model Applier, which can help predict the likelihood of a chemical structure being carcinogenic or genotoxic by comparing it against a library of other structures. This is utilized where experimental data of the chemical in question is unavailable.

    The toxicologist can also build a toxicity profile in support of product safety. This is tailored to the relevant regulatory pathway based on the existing hazard data, published scientific studies and expert body reviews. Toxicologists can also produce a quantitative risk assessment and create a comprehensive regulatory report evaluating the potential health risks associated with both individual ingredients and the whole product. These reports would be the output from the literature review and subsequent toxicology assessments.

    Due to the scale and complexity of the task, many NGP manufacturers choose to outsource their literature searches to a trusted analytical testing and integrated consulting partner. This partner can then provide swift expert toxicological advice to ensure the product is safe and compliant with relevant regulatory requirements while saving the manufacturer time and ensuring quality.

  • Inter Scientific joins UKVIA

    Inter Scientific joins UKVIA

    Inter Scientific, an analytical testing and regulatory compliance firm, has joined the U.K. Vaping Industry Association (UKVIA).

    “We are thrilled to join UKVIA as a full board member and contribute to the advancement of the vaping industry in the U.K.,” said Inter Scientific CEO David Lawson.

    “At Inter Scientific, we believe in the potential benefits to public that the vape industry holds. Our collaboration with UKVIA will enable us to work closely with industry leaders to ensure the highest standards of safety, quality and compliance are met to benefit consumers and public health.”

    Inter Scientific says it will actively engage in initiatives aligned with the UKVIA’s strategic objectives. “We will uphold the highest quality standards to demonstrate the industry’s responsibility, promote sector growth and its economic contribution,” the company wrote on its website.

    “Addressing misinformation about vaping will be a priority, aiming to correct misconceptions and highlight vaping as a beneficial tool for smoking cessation. Additionally, we aim to foster acceptance and support from the public health community, emphasizing vaping’s role in improving public health outcomes.”

  • Due Diligence

    Due Diligence

    Photo: Eugene

    Testing and toxicology of heated-tobacco products

    By Malcolm Saxton

    Heated-tobacco products (HTPs) are a type of reduced-risk nicotine device that offer a similar experience to combustible cigarettes but can help reduce exposure to potentially harmful toxicants. With the pressure on manufacturers to develop safer, smoke-free alternatives, Malcolm Saxton, senior consultant, chemistry, at Broughton, shares insight into the testing and toxicology associated with HTPs.

    In combustible cigarettes, temperatures can reach up to 950 degrees Celsius. As well as liberating the nicotine, this process breaks the tobacco down to produce over 8,000 known chemicals. However, in HTPs, tobacco is not burnt—the maximum temperature is 350 degrees Celsius, providing enough heat to liberate nicotine and aroma without being high enough to result in combustion. Instead, a pyrolytic process known as torrefaction takes place, which is the same process that occurs when roasting coffee beans to release flavor.

    The absence of combustion substantially reduces the number of chemicals released, with harmful and potentially harmful constituents (HPHCs) in HTP aerosols shown to be significantly reduced from cigarette smoke. Data from the Philip Morris International Scientific Update showed a 90 percent to 95 percent reduction in the average levels of HPHCs in the aerosol of IQOS,* the leading HTP brand, compared with combustible 3R4F reference cigarettes. In addition, there is thought to be little youth appeal.

    Due to their reduced-risk profile and similarity in experience to smoking combustible cigarettes, interest in HTPs is growing, and IQOS now has around 20 million users worldwide.

    Bringing an HTP to Market

    Most countries do not have specific regulations for HTPs but regulate them in the same way as either combustible cigarettes or alternative tobacco products. In the EU and U.K., HTPs are regulated by the Tobacco Products Directive and the Tobacco and Related Products Regulations, respectively, which carry stringent requirements for testing, packaging and more.

    In the U.S., HTPs are regulated using the premarket tobacco product application (PMTA) or the modified-risk tobacco product (MRTP) process, with the PMTA being the established route to market. There are very few products that have been submitted and granted a PMTA or an MRTP from the U.S. Food and Drug Administration, which is required to make reduced-risk claims.

    To have the best chance of approval, it can be beneficial to work with a partner that offers a fully integrated service that covers product development, extractables and leachables, testing and characterization, toxicology, stability studies, and regulatory consultancy. In addition to freeing up internal capacity, outsourcing testing and toxicological assessments can help streamline the product design and regulatory application process, benefiting from the partner’s previous experience.

    Toxicological Considerations

    HTPs are intended to be a smoking cessation tool, so they must be tested to ensure a reduced toxicological risk compared with conventional combustible products. In addition, the individual toxicological risk profile should be understood to establish that new hazards are not introduced or that current ones have not increased. The first three stages of evaluating an HTP typically include: evaluating product design, testing aerosol chemistry and performing a toxicological assessment.

    The product design will vary based on the type of HTP, which can be electrically heated, carbon heated or aerosol heated. Heating mechanisms can comprise a resistive heat-blade system or may use induction heating. Product design is important in achieving an appropriate yield and aerosol cloud without increasing risk, and iterative testing can help ensure optimal design. Working with a partner who understands the intricacies of product design and how it impacts toxicological risk and regulatory approval can ensure manufacturers get it right the first time.

    The composition of the HTP aerosol will depend on the product design, including the materials in the hardware as well as the ingredients, such as flavors. Desk-based toxicology, including a literature search, can help assess whether listed ingredients and materials are associated with anything that is of high concern.

    Aerosol testing requirements vary according to the purpose of testing and the regulatory framework being followed. At the most basic, the EU and U.K. require a minimum of tar (nicotine-free dry particulate matter), nicotine and carbon monoxide. Other priority toxicant lists for cigarettes have been developed by a number of organizations, including the FDA, Health Canada and the World Health Organization Study Group on Tobacco Product Regulation. The most widely accepted list of HPHCs to test in the aerosol of HTPs, both for regulatory submission and for producing evidence of potential harm reduction, is the PMI-58, a list developed specifically by PMI to focus on analytes most relevant to IQOS and more generally HTPs.

    Analytical chemists will design a testing protocol that includes all relevant parameters for regulatory approval. For example, PMTAs typically require more data than other markets, and the testing package may need to be more rigorous as a result.

    The aerosol HPHC profile forms the basis of risk reduction characterization for various human diseases, such as cancer and respiratory disease, and can be contextualized against a combustible cigarette to establish the level of harm reduction. Exposure assessments can be generated from product-specific data by looking at how the product is used in the market or by using data from the literature.

    Compiling the relevant analytical testing and toxicological information for an HTP can be a challenging task. Working with an expert partner can make the process easier, reducing strain on resources and complementing the skills of an in-house team.

    *Afolalu EF, Langer P, Fischer K, Roulet S, Magnani P. Prevalence and patterns of tobacco and/or nicotine product use in Japan (2017) after the launch of a heated-tobacco product (IQOS): a cross-sectional study. F1000Res. 2021 Jun 25;10:504. doi: 10.12688/f1000research.52407.2. PMID: 35528952; PMCID: PMC9069173.

  • Coresta Congress Registration Opens

    Coresta Congress Registration Opens

    Photo: Anthony Brown

    Registration is open for the 2024 Coresta Congress in Edinburgh, Scotland, Oct. 13–17.

    The theme for the congress is Advancing Tobacco Harm Reduction Through Scientific Collaboration.

  • Trust in Industry-Funded Science Growing: Study

    Trust in Industry-Funded Science Growing: Study

    Photo: BAT

    Public trust in tobacco industry-funded scientific research is growing, according to a new study co-authored by researchers in the Tobacco Control Research Group at the University of Bath, University of Colorado and University of Bristol.

    The researchers aimed to understand the extent to which the public trusts Philip Morris International’s involvement in science. They asked 1,580 U.K. residents were asked to rate their level of trust in: PMI, the Foundation for a Smoke-Free World (recently rebranded as Global Action to End Smoking), or Cancer Research UK (CRUK), on a scale from 1 (no trust) to 7 (complete trust). CRUK was selected as a control group as a highly trusted scientific organization, wholly independent from the tobacco industry.

    Overall trust in PMI was 4.66, compared to 5.79 out of 7 in CRUK. Overall trust for the Foundation for a Smoke-Free World was 5.04. After participants were informed that FSFW is funded by the tobacco industry, the overall trust rating dropped to 4.77.

    “This work is important because tobacco companies use their involvement in science as ‘proof’ that they are credible research organizations,” said lead author Tess Legg in a statement. “They also funnel research funds through third-party companies and historically this has involved attempts to obscure their involvement in the resulting science.”

    The study’s authors warn against acceptance of tobacco industry funding and dissemination of scientific findings

    “As it stands, FSFW still has an immense amount of money from PMI at its disposal and so the risk of it continuing to further the industry’s interests is high,” Legg said. “Our findings suggest that more needs to be done by the tobacco control and public health communities to help the U.K. public understand how underhand the tobacco industry’s attempts to rebrand really are, and to stop scientific front groups from muddying the water by lending the industry an air of credibility.”

  • Scientist Urges Caution With AI Vaping Studies

    Scientist Urges Caution With AI Vaping Studies

    Marina Murphy is a scientific communications and engagement expert with more than 20 years of experience.

    Scientists should be aware of the “illusions of understanding” when relying on artificial intelligence for their research, warned Marina Murphy, industry veteran and scientific adviser to the U.K. Vaping Industry Association.

    A recent study, published in Scientific Reports, claims to have uncovered potentially harmful substances that are produced when e-liquids in vaping devices are heated for inhalation.

    The research team at the Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, used artificial intelligence to simulate the effects of heating e-liquid flavor chemicals found in nicotine vapes.

    The analysis revealed the formation of many hazardous chemicals, including 127 that are classified as “acute toxic,” 153 as “health hazards” and 225 as “irritants.” Notably, these included a group of chemicals called volatile carbonyls (VCs), which are known to pose health risks. Sources for VCs were predicted to be the most popular fruit-flavored, candy-flavored and dessert-flavored products.

    Lead author Donal O’Shea, professor of chemistry and head of the department, said the findings are concerning. “Our findings indicate a significantly different profile of chemical hazards compared to what we are familiar with from traditional tobacco smoking. It is plausible that we are on the cusp of a new wave of chronic diseases that will emerge 15 [years] to 20 years from now due to these exposures.”

    Murphy countered that the effects of overheating e-liquids have been studied extensively. “This can lead to the production of carbonyls, for example, but these compounds make the vapor so caustic as to be un-inhalable,” she wrote in response to the RCSI study. “Newer e-cigarette devices are designed with built-in temperature control systems.”

    She warned that “scary headlines” could prompt smokers thinking of switching to less harmful e-cigarettes to stick with conventional cigarettes instead.

    “Vaping has proven to be the most popular quit aid, and we need to focus less on problems and more on solutions to ensure that vapers continue to get the flavors they need to successfully quit cigarettes in the safest way possible,” said Murphy.

  • Vaping Additives Harm Lung Membrane: Study

    Vaping Additives Harm Lung Membrane: Study

    Panagiota Taktikakis (left) and Christine DeWolf (Photo: Concordia University)

    The e-cigarette additive tocopherol—an organic compound better known as vitamin E—and tocopherol acetate can damage the lungs, according to two Concordia University researchers writing in Langmuir.

    When heated and inhaled, the compound embeds in the pulmonary surfactant, a nanoscopically thin lipid protein membrane coating the surface of the alveoli that regulates the oxygen-carbon dioxide gas exchange and stabilizes the lungs’ surface tension during breathing.

    The researchers used one-molecule-thick model membranes called Langmuir films to simulate the expansion and compression of the pulmonary surfactant. They then added vitamin E, which is structurally similar to the lipids found in the membrane.

    They used different observational techniques including microscopy, x-ray diffraction and x-ray reflectivity. The researchers observed how the presence of the additive changed the surfactant’s properties and monitored changes as they added more to simulate how a real surfactant would accumulate and retain the compound in the lungs.

    “We can see that the presence of vitamin E changes the functional properties of the surfactant,” said Christine DeWolf, a professor in the Department of Chemistry and Biochemistry and co-founder of the Centre for NanoScience Research at Concordia University, in a statement.

    “Oxygen is exchanged for carbon dioxide across the pulmonary surfactant, so if the surfactant properties are altered, so can be the ability for gas to be exchanged. And if the surface tension is changed, that affects the work of breathing. So combined, these changes make breathing more difficult. We think this is the molecular basis contributing to the shortness of breath and reduced oxygen levels seen in people suffering from EVALI [electronic cigarette or vaping product use–associated lung injury]”

    This paper is the first of a larger project that looks at the components of the vaping solutions that deliver the nicotine or cannabinoids to users.

    “Many of the components in these solutions are approved by the United States Food and Drug Administration for other uses,” DeWolf says. “But the high heating rates needed to vaporize these components can cause further chemical reactions to occur. The components that are actually being inhaled may not be the ones in the original e-liquid.”