A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks

Regul Toxicol Pharmacol. 2016 Nov 15:81 Suppl 1:S1-S14. doi: 10.1016/j.yrtph.2016.10.003. Epub 2016 Oct 18.


A randomised, parallel group clinical study was performed to evaluate the safety profile of an e-vapour product (EVP; 2.0% nicotine) in smokers of conventional cigarettes (CCs) switching to use the EVP for 12 weeks. During the study, no clinically significant product-related findings were observed in terms of vital signs, electrocardiogram, lung function tests and standard clinical laboratory parameters. Adverse events (AEs) reported by EVP subjects were more frequent during the first week after switching to the EVP. The frequency of AEs reduced thereafter and out of a total of 1515 reported AEs, 495 were judged as being related to nicotine withdrawal symptoms. The most frequently stated AEs were headache, sore throat, desire to smoke and cough reported by 47.4, 27.8, 27.5 and 17.0% of subjects, respectively. Only 6% of AEs were judged as probably or definitely related to the EVP. Additional observations in EVP subjects included a decrease in the level of urine nicotine equivalents by up to 33.8%, and decreases in the level of three biomarkers of exposure to toxicants known to be present in CC smoke (benzene, acrolein and 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone). The decrease in nicotine equivalents coincided with an increase in nicotine withdrawal symptoms, measured by a questionnaire, which subsided after two weeks. The data presented here shows the potential EVPs may offer smokers looking for an alternative to CCs.

Keywords: Adverse events; Biomarkers of biological effect; Biomarkers of exposure; Cigarette; Clinical study; Electronic cigarette; Electronic vapour product; Safety; Smoking urges; Withdrawal symptoms.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • Consumer Product Safety
  • Electronic Nicotine Delivery Systems* / adverse effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage*
  • Nicotine / adverse effects
  • Nicotinic Agonists / administration & dosage*
  • Nicotinic Agonists / adverse effects
  • Risk Assessment
  • Smoking / adverse effects
  • Smoking / blood
  • Smoking / urine
  • Smoking Cessation / methods*
  • Smoking Prevention*
  • Substance Withdrawal Syndrome / etiology
  • Surveys and Questionnaires
  • Time Factors
  • Tobacco Use Disorder / therapy*
  • United Kingdom
  • Volatilization
  • Young Adult


  • Biomarkers
  • Nicotinic Agonists
  • Nicotine