Pharmacokinetic Profile of Toxic Substances and Nicotine in Electronic Cigarettes: a Randomised Cross-over Trial KINECIG

The study is randomised cross-over trial designed to compare: 1) serum nicotine levels of four different e-Cigarette strength ; 2) Serum levels of carcinogenic and toxic substances will be also compared. Participants will be requested to abstain from smoking and alcohol from 20:00 on the night before each study day and from food and caffeine for at least 1 h before the session. On arrival at the study centre, carbon monoxide (CO) will be measured in participants' expired breath. If CO will be less than 15 parts per million (ppm), the assigned study treatment will be allocated; however, if CO was > 15 ppm or they will report smoking in the previous 12 h, participants will be rescheduled wherever possible to a subsequent session.

On the first study day, participants will be randomised to use one of five ordered conditions (each separated by 3 day): ENDDs (fourth generation) containing nicotine 2,4%; ENDDs (second generation) containing nicotine 7,4 mg; ENDDs containing nicotine 9 mg; ENDDs nicotine free; their usual cigarette. Additionally participants will be trained to use an electronic cigarette. The following tests will be completed at the each visits: Aldehydes; ROM/TOS; Total thiols; Nicotine; Hydroxypyrene; Cotinine; 1,3-butadiene; Acrylonitrile. After, they will be cannulated and serial venous blood samples for Aldehydes; ROM/TOS; Total thiols; Nicotine will be collected at 0.5, 2, 5, 15, 30 and 60 min after being instructed to take 10 puffs. Additionally, levels of carbon monoxide in exhaled breath (eCO) will be measured 0.5, 2, 5, 15, 30 and 60 min after being instructed to take 10 puffs. At 60 min, after being instructed to take 10 puffs, urine sample for Hydroxypyrene; Cotinine; 1,3-butadiene; Acrylonitrile will be collected. Participants then will leave the study centre with instructions to continue their usual daily activities and to use the study product regularly (for at least 10 hrs) and freely throughout the day. At bedtime and after the puffing chronic phase, when participants will use the study product regularly for at least 10 hrs, urine sample for Hydroxypyrene; Cotinine; 1,3-butadiene; Acrylonitrile will be collected. Participants will be allowed to smoke as they will wish once these measures will be collected and during the 3-day washout period between each study day.