a 2013 study examined 33 countries and found that only 1% of the adult smokers exclusively used non-nicotine e-cigarettes. a cartridge may contain 0 to 20 mg of nicotine. refill liquids are often sold in the size range from 15 to 30 ml. e-liquids are frequently sold in dropper bottles. one cartridge may typically last as long as one pack of cigarettes. a refill bottle can contain up to 100 mg/ml of nicotine, which is meant to be diluted before use. some users, probably due to financial reasons and the willingness to experiment, are opting to make homemade e-liquids. a small percentage of liquids without flavoring is also sold. the flavorings may be natural or artificial. certified organic e-liquid is also sold. about 8,000 flavors existed in 2014. more than 15,500 flavors existed in 2018. a user does not normally consume a whole cartridge in a single session. most e-liquids are produced by a few manufacturers in china, the us, and europe. an e-cigarette user will usually obtain 300 to 500 puffs per ml of e-liquid. a 2017 survey found that 62.2% of everyday e-cigarette users stated using lower than 4 ml daily and 1.5% used higher than 10 ml daily. 18.1% of everyday e-cigarette users were not aware of the amount of e-liquid they use. manufacturing e-liquids are manufactured by many producers, both in the us and across the world. first tier manufacturers use lab suits, gloves, hair covers, inside of certified clean rooms with air filtration similar to pharmaceutical-grade production areas. standards e-liquid manufacturing requirements under the us food and drug administration (fda) rules include report user fee information, pay user fees, register their establishment and submit list of products, including labeling and advertisements, submit health documents, submit ingredient listing, include required warning statements on packages and advertisements, submit quantities of harmful and potentially harmful constituents, and submit a modified risk tobacco product application. the revision to the eu tobacco products directive has some standards for e-liquids. standards for e-liquid manufacturing have been created by american e-liquid manufacturing standards association (aemsa), which is trade association dedicated to creating responsible and sustainable standards for the safe manufacturing of e-liquids used in vapor products. aemsa has published a comprehensive list standards and best known methods, which are openly available for use by any manufacturer of e-liquids. the aemsa standards cover nicotine, ingredients, sanitary manufacturing rooms, safety packaging, age restrictions, and labeling. aemsa guidelines recommend that the nicotine levels in e-liquids be within the amount of ±10% from the levels stated on the label. regulation effective august 8, 2016, under the fda rules, a company that mixes or prepares e-liquids is regulated as a tobacco product manufacturer. under the same regulation, a company that sells e-liquids is regulated as a tobacco retailer. companies who import or try to sell for import into the us must conform to the federal food, drug, and cosmetic act. the 2016 fda ruling did not incorporate regulation concerning flavoring of e-cigarettes. industry standards have been created and published by the american e-liquid manufacturing standards association (aemsa). the fda authority to regulate e-liquids was announced in may 2016. the fda has sought to regulate e-liquid in 2014 through use of the family smoking prevention and tobacco control act, passed into law in june 2009. in april 2014, the fda issued its "deeming" proposals for public comment, which would cover e-liquids manufacturing. manufacturers of e-liquid in the uk are required to inform the government regarding the content in each liquid. the eu tobacco products directive requires e-liquids to be tested 6 months before they are sold. the tobacco products directive in the eu limits the sale of e-liquid. it can only be sold in 10 ml bottles, which need to have a child-proof closure. they have to be pre-registered to the medicines and healthcare products regulatory agency before sale. there is also a limit on the nicotine content, meaning the nicotine strength of any e-liquid cannot exceed 20 mg/ml (2.0%). refill liquids in the eu with more than 20 mg/ml of nicotine may be sold with prior authorization from the pharmaceutical regulation. as of january 2020, the food and drug administration put new regulations on the flavor of e-liquids. they ban companies from manufacturing any juices or pre-filled pods that contained fruity or minty flavors. this restriction also banned stores from selling any flavors of e-liquid that are fruity or minty that could have been imported from a different country. nicotine yield smoking a traditional cigarette yields between 0.5 and 1.5 mg of nicotine, but the nicotine content of the cigarette is only weakly correlated with the levels of nicotine in the smoker's bloodstream. the amount of nicotine in the e-cigarette aerosol varies widely either from puff-to-puff or among devices of the same company. in practice e-cigarette users tend to reach lower blood nicotine concentrations than smokers, particularly when the users are inexperienced or using first-generation devices. nicotine in cigarette smoke is absorbed into the bloodstream rapidly, and e-cigarette aerosol is relatively slow in this regard. vaping typically gives a lower amount of nicotine per puff than smoking cigarettes. e-liquids contain nicotine in a variety of different strengths. from no nicotine to 36 mg/ml. on average a regular cigarette contains 6–28 mg of nicotine or the user will inhale about 1.1 to 1.8 mg of nicotine if just a portion is used. on average an e-cigarette contains 0.5-15.4 mg of nicotine per 15 puffs. in practice the nicotine concentration in an e-liquid is not a reliable guide to the amount of nicotine that reaches the bloodstream. notes the liquid composition of each brand of e-cigarettes may differ, making it difficult to generalize about the potential toxic properties of these devices. bibliography mcneill, a; brose, ls; calder, r; bauld, l; robson, d (february 2018). "evidence review of e-cigarettes and heated tobacco products 2018" (pdf). uk: public health england. pp. 1–243. stratton, kathleen; kwan, leslie y.; eaton, david l. (january 2018). public health consequences of e-cigarettes (pdf). national academies of sciences, engineering, and medicine. national academies press. pp. 1–774. doi:10.17226/24952. isbn 978-0-309-46834-3. pmid 29894118. mcneill, a; brose, ls; calder, r; hitchman, sc; hajek, p; mcrobbie, h (august 2015). "e-cigarettes: an evidence update" (pdf). uk: public health england. pp. 1–113. weingarten, a (march 2018). "welcome to the world of sub-ohm vaping" usa: industry trades