cinnamaldehyde, and isovaleraldehyde. A 2012 study found butterscotch flavor was highly toxic with one liquid and two others had a low toxicity. A 2014 in vitro study demonstrated that e-cigarette use of a "balsamic" flavor with no nicotine can activate the release of proinflammatory cytokine in lung epithelial cells and keratinocytes. Some additives may be added to reduce the irritation on the pharynx. The long-term toxicity is subject to the additives and contaminants in the e-liquid. Certain e-liquid flavorings contain diacetyl and acetyl propionyl which give a buttery taste. Diacetyl and acetyl propionyl are associated with bronchiolitis obliterans ("popcorn lung"), a serious lung disease. A 2015 review recommended for specific regulation of diacetyl and acetyl propionyl in e-liquid, which are safe when ingested but have been associated with respiratory harm when inhaled. Both diacetyl and acetyl-propionyl have been found in concentrations above those recommended by the US National Institute for Occupational Safety and Health. Diacetyl is normally found at lower levels in e-cigarettes than in traditional cigarettes. Concerns exist that the flavors and additives in e-cigarettes might lead to diseases, including the popcorn lung. The cardiovascular effects, including a vast range of flavorings and fragrances, is unknown. The irritants butyl acetate, diethyl carbonate, benzoic acid, quinoline, bis(2-ethylhexyl) phthalate, and 2,6-dimethyl phenol were present as undeclared ingredients in the e-liquid. Hindering safety assessments of e-liquids is the fact that the precise ingredients of e-cigarettes and e-liquids are not known. With the current popular trend of flavored e-cigarettes use among young generations, there is concern about the potential long-term health of the public. Heated tobacco products Heated tobacco products are frequently flavored. It is possible that these products could appeal to non-smokers, especially since they are available in various flavors. Hookah Muʽassel (also known as shisha), the tobacco product used in hookahs, is almost always flavored: more than 85% of mu'assel sold in the United States is flavored. Typical flavors include apple, plum, coconut, mango, mint, strawberry and cola, with mint and double apple () being the most popular. Unusual flavors, including white gummy bear, blueberry muffin, spiced chai and Powerbull flavor (similar to the flavor of a Red Bull energy drink), have been introduced in recent years by modern tobacco companies. Heating these flavorings releases toxic chemicals and carcinogens such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), furans, phenols, aldehydes (such as acrolein), and acids, in addition to nitrogenous carcinogens,