Addictiveness and sttractiveness of tobacco additives

SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks): et al.The Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) has been asked to evaluate the role of tobacco additives in the addictiveness and attractiveness of tobacco products. The criteria for dependence established in humans indicate that tobacco has a high addictive potential, but it remains difficult to assess the addictiveness of individualadditives. In animal studies the addictive potency of the final tobacco product cannot be assessed. The reinforcing potency of drugs is measured after intravenous injections and suggests that the abuse liability of pure nicotine is weaker than the addictive potential of tobacco products in humans. The currently used methods to define addictiveness of nicotine and additives are thus not considered adequate. In humans, the positive correlation between tobacco consumption and dependence suggests that individuals with high nicotine levels in their blood are more dependent. In animal studies using self-administration, an inverted U-shaped dose-response curve has generally been revealed suggesting that the addictiveness of nicotine is not directly linearwith the dose. There is however substantial variation in the response to nicotine in both animals and humans, and genetic factors probably play an important role. No tobacco additives which are addictive by themselves have so far been identified. However, sugars, polysaccharides and cellulose fibres which are naturally present in tobacco, or sugars added in high quantities to most tobacco products, give rise to numerous aldehydes, such as acetaldehyde, in tobacco smoke. Acetaldehyde given intravenously is self-administered and enhances the addictiveness of nicotine in experimental animals. Additives that facilitate deeper inhalation (e.g. menthol) or inhibit the metabolism of nicotine may enhance the addictiveness of nicotine indirectly. Substances such as ammonia that increase the pH of the tobacco and the smoke, result in higher amounts of uncharged nicotine. However, it is uncertain if more nicotine isabsorbed with higher smoke pH. For smokeless tobacco it seems that an increased pH enhances nicotine absorption in the mouth.The methods used to quantify the addictive potency of additives have limitations because of technical challenges in experimentally manipulating the presence or absence of anadditive in a tobacco product. Such experiments require large technical and financial resources. In addition, there are ethical issues if testing in humans is considered. Due to these limitations, the available methodologies are not considered adequate. A number of technical characteristics of cigarettes (paper, filter, packing, geometry) influence the content of different substances in the smoke and the size of smoke particles. Many smokers compensate for a lower dose of nicotine by increasing puff volume and frequency, and by deeper inhalation. The particle size of the smoke aerosol does not seem to substantially influence the exposure to nicotine. The technical characteristics of cigarettes may thus modulate smoking behaviour but it is uncertain if this leads to a higher risk of addiction. Attractiveness is defined as the stimulation to use a product. The attractiveness of tobacco products may be increased by a number of additives but is also influenced by external factors such as marketing, price etc. Animal models do not currently exist for the assessment of attractiveness. In humans, the attractiveness of individual tobaccoproducts may be compared in panel studies, surveys, and by experimental measures. Another method is to experimentally adjust tobacco products to exclude or include individual additives and test responses to them. However, this type of research is difficult due to ethical considerations that will usually preclude human testing of tobacco products, particularly among non-users or children. The use of fruit and candy flavours seems to favour smoking initiation in young people. Menthol also attracts a number of smokers, in particular African Americans. Some additives decrease the harshness and increase the smoothness of the smoke. Certain additives yield a full and white smoke and other additives reduce the lingering odour of the smoke in order to favour the acceptability of smoking to people around. Additives considered attractive may in principle lead to brand preference or a higher consumption of tobacco products. However, it remains difficult to distinguish the direct effects of these additives from indirect effects such as the marketing towards specific groups.Peer Reviewe

Anoxic thermal degradation of kānuka and tobacco between 180°C and 390°C : a comparative study : a thesis presented in partial fulfilment of the requirements for the degree of Masters of Engineering in Chemical and Bioprocess Engineering at Massey University, Manawatu, New Zealand

Heat-not-burn (HnB) devices are a recent innovation used to heat tobacco and other herbal material to temperatures up to 350°C, which are significantly below those typical of cigarettes. Similarly, wood smoke for food smoking is made at temperatures between 280-350°C in friction smokers, to far higher in smouldering combustion systems where local temperatures are similar to cigarettes. The drive towards lower temperature smoke generation is to allay concerns about harmful compounds that are produced at higher temperatures. The most well-known of these are polycyclic aromatic hydrocarbons (PAHs). Most research in tobacco smoking has naturally focussed on smouldering combustion up to 950°C. This research reported here is aimed at low temperatures, 180°C to 390°C, and in anoxic conditions. It compares two types of tobacco - loose leaf tobacco for roll-your-own cigarettes and HEETS which are a Phillip Morris cigarette used in the Philip Morris iQOS device - and kānuka wood, to understand the similarities and differences in energetics and compound formation. The analytical techniques used were thermogravimetric analysis (TGA), simultaneous thermal analysis using thermogravimetry and differential scanning calorimetry (STA-TG/DSC), evolved gas analysis mass spectrometry (EGA/MS), pyrolysis gas chromatography mass spectrometry (Py-GC/MS) and scanning electron microscopy (SEM). HEETS and tobacco have a weight loss event prior to pyrolysis, related to the evaporation of low molecular mass compounds, the most prominent being nicotine, but also the additive glycol. The degradation of hemicellulose, cellulose and lignin can be seen in the thermogravimetric data. Kānuka degradation occurs at higher temperatures than the tobaccos, likely due to greater cellulose crystallinity. The heat of pyrolysis trends from endothermic for very small samples to more exothermic for larger sample masses, due to the greater tortuous path distance that the escaping volatiles must travel leading to more secondary reactions. Tobacco and HEETS become exothermic with increasing sample size more quickly than kānuka. They have ten times the ash, which will catalyse reactions. The EGA/MS and Py-GC/MS identified the expected degradation compounds like acetic acid, furfural, mequinol, syringol, levoglucosan and isoeugenol. As a function of temperature, few degradation compounds were present at 180°C, but more appeared with temperature. PAHs were identified. Small molecule PAHs appear at 180°C and increase with temperature. The largest PAHs generally did not appear at 390°C. Specific nitrogen compounds are seen in the tobacco vapours, arising from nicotine (C₁₀H₁₄N₂) and tobacco specific nitrosamines. This research has shown that compounds, like highly carcinogenic benzo(a)pyrene, are less prominent at temperatures below 350°C. Tobacco and kānuka are both plant biomass and have similar components, although the high ash content of tobacco and the large cellulose crystalline structure of kānuka lead to compounds being released from kānuka at higher temperatures. If heat-not-burn technology was applied to wood smoke a higher set point temperature would be required. Overall, this research has shown the dynamics of low temperature heating although more research has been done to quantify health risks. Knowing how composition is affected by temperature is important for improving operational safety and minimizing chemical hazard risk of low temperature devices

Method Development and Applications for Reduced-Risk Products in Separation Science

In recent years, there has been rapid growth in the availability of innovative, non-combustible products, including oral tobacco-derived nicotine (OTDN) products, heated tobacco products (HTPs), and electronic cigarettes (also referred to as e-vapor products; EVPs). Industry, academic, and government researchers are developing and validating analytical methods to extract, separate, identify, and quantitate a variety of analytes from these innovative tobacco products using a wide range of analytical techniques. These analytes include constituents such as nicotine, degradants and impurities, flavors, non-tobacco ingredients, HPHCs, and other currently unknown constituents. In this Special Issue, we received nine contributions that covered the latest analytical methods that have been developed and applied for the chemical characterization or exposure assessment to tobacco product constituents of innovative non-combustible products. This Special Issue is representative of the importance of analytical sciences research in characterizing innovative non-combustible products for guiding product design, determining relative product performance, ensuring consistency during the manufacturing process, informing toxicological risk assessment, and enabling regulatory reporting. The current advances in the development and applications of the analytical methods reported in this Special Issue can be used to inform the harm reduction potential of innovative non-combustible products for adult smokers

Chromatographic analysis and survey studies to evaluate the emerging drugs of synthetic cannabinoids in Scotland and Saudi Arabia

Synthetic cannabinoid receptor agonists or more commonly known as synthetic cannabinoids (SCs) were originally created to obtain the medicinal value of THC but they are an emerging social problem. SCs are mostly produced coated on herbal materials or in powder form and marketed under a variety of brand names, e.g. “Spice”, “K2”. Despite many SCs becoming controlled under drug legislation, many of them remain legal in some countries around the world. In Scotland, SCs are controlled under the Misuse of Drugs Act 1971 and Psychoactive Substances Act 2016 that only cover a few early SCs. In Saudi Arabia, even fewer are controlled. The picture of the SCs-problem in Scotland is vague due to insufficient prevalence data, particularly that using biological samples. Whilst there is evidence of increasing use of SCs throughout the world, in Saudi Arabia, there is currently no data regarding the use of products containing SCs among Saudi people. Several studies indicate that SCs may cause serious toxicity and impairment to health therefore it is important to understand the scale of use within society. A simple and sensitive method was developed for the simultaneous analysis of 10 parent SCs (JWH-018, JWH-073, JWH-250, JWH-200, AM-1248, UR-144, A-796260, AB-FUBINACA, 5F-AKB-48 and 5F-PB-22) in whole blood and 8 corresponding metabolites (JWH-018 4-OH pentyl, JWH-073 3-OH butyl, JWH-250 4-OH pentyl, AM-2201 4-OH pentyl, JWH-122 5-OH pentyl, JWH-210 5-OH pentyl, 5F-AKB-48 (N-4 OH pentyl), 5F-PB-22 3-carboxyindole)in urine using LLE and LC-MS/MS. The method was validated according to the standard practices for method validation in forensic toxicology (SWGTOX, May 2013). All analytes gave acceptable precision, linearity and recovery for analysing blood and urine samples. The method was applied to 1,496 biological samples, a mixture of whole blood and urine. Blood and/or urine samples were analysed from 114 patients presenting at Accident and Emergency in Glasgow Royal Infirmary, in spring 2014 and JuneDecember 2015. 5F-AKB-48, 5F-PB-22 and MDMB-CHMICA were detected in 9, 7 and 9 cases respectively. 904 urine samples from individuals admitted to/liberated from Scottish prisons over November 2013 were tested for the presence of SCs. 5F-AKB-48 (N-4 OH pentyl) was detected in 10 cases and 5F-PB-22 3-carboxyindole in 3 cases. Blood and urine samples from two post-mortem cases in Scotland with suspected ingestion of SCs were analysed. Both cases were confirmed positive for 5F-AKB-48. A total of 463 urine samples were collected from personnel who presented to the Security Forces Hospital in Ryiadh for workplace drug testing as a requirement for their job during July 2014. The results of the analysis found 2 samples to be positive for 5F-PB-22 3carboxyindole. A further study in Saudi Arabia using a questionnaire was carried out among 3 subpopulations: medical professionals, members of the public in and around smoking cafes and known drug users. With regards to general awareness of Spice products, 16%, 11% and 22% of those participants of medical professionals, members of the public in and around smoking cafes and known drug users, respectively, were aware of the existence of SCs or Spice products. The respondents had an overall average of 4.5% who had a friend who used these Spice products. It is clear from the results obtained in both blood and urine testing and surveys that SCs are being used in both Scotland and Saudi Arabia. The extent of their use is not clear and the data presented here is an initial look into their prevalence. Blood and urine findings suggest changing trends in SC use, moving away from JWH and AM SCs to the newer 5F-AKB-48, 5-F-PB-22 and MDMBCHMICA compounds worldwide. In both countries 5F-PB-22 was detected. These findings clarify how the SCs phenomenon is a worldwide problem and how the information of every country regarding what SCs are seized can help and is not specific for that country. The analytes included in the method were selected due to their apparent availability in both countries, however it is possible that some newer analytes have been used and these would not have been detected. For this reason it is important that methods for testing SCs are updated regularly and evolve with the ever-changing availability of these drugs worldwide. In addition, there is little published literature regarding the concentrations of these drugs found in blood and urine samples and this work goes some way towards understanding these