Developing an efficient E-cigarette aerosol generation and exposure system for rodent models with aerosol characteristics equivalent to those inhaled by E-cigarette users

Abstract E cigaretteE ciguse has rapidly proliferated worldwideIt is speculated that E cig use may exceed conventional cigarette use withinyearsCigarette smoking is the leading preventable cause of death and disabilityAs E cigs are a relatively new productstudies are needed to determine their long term detrimental effectssome of which may be similar to the long term detrimental effects of nicotineThe lack of an appropriate method for E cig delivery to animals and lack of an appropriate animal model are major barriers of the research fieldWe propose to develop a system designed for E cig exposure to rodent modelsWe propose that E cig exposure using our system can generate clinically relevant animal models with nicotine levels PK comparable to those of human E cig users for research of E cig effects on human healthand allow investigators to uncover potential detrimental and beneficial effects related to E cigsAimTo design and make a prototype for a product of efficient E cig aerosol generation and exposure system delivering Ecig aerosol to rodent sthrough inhalation with characteristics equivalent to those inhaled by human E cig usersThis system includes hardware and software that control the number of E cigs and timing of activation so as to regulate the dose of aerosol exposureThis device has variable E cig holders for different sizes of E cigs available in the marketand generates aerosol for testing different brands of E cigs of investigatorsandaposchoiceWe will characterize the E cig aerosol by measuring the aerosol particle size distribution and mass concentration in the breathing zone of the rodent exposure chamber to verify that the aerosol characteristics are equivalent to those in mainstream E cigs that human E cig smokers inhaleAimTo validate this E cig aerosol generation and exposure system with acute and chronic animal experiments to show that it produces E cig animal models with nicotine PK comparable to that in human E cig usersWe will measure plasma nicotine and cotinine levels at a series of time points during and after rats or mice are exposed to E cig aerosol in a free moving or nose only chamberWe will optimize the parameterse gnumber of E cigs and duration activatedof aerosol generation and exposure and determine if the system can generate rodent models with the concentrations of nicotine and cotinine resembling that in human ENDS users or other levels PK as investigators choose for their research purposesOur products will meet the need of the E cig research community and greatly advance the field to enable testing potential toxicities of Ecig in animal modelsOur products will be a powerful tool for studying the effects of E cig smoking on cardiovascularrespiratory and nervous systemson metabolismpregnancydevelopment as well as teratogenicity and addiction of E cigsTherefore it will help inform regulators about the potential toxicity of Ecig productsWe planin a future phase II projectto develop a commercial product line of E cig generation and exposure systems including E cig self administration for rodents Project Narrative As E cigs are a relatively new productstudies are needed to determine their long term detrimental effects on users while appropriate methods and devices for E cig exposure to animal models are lackingWe propose to develop a system designed for E cig exposure to rodent modelsThis system can generate clinically relevant animal models with nicotine levels pharmacokinetics comparable to those of human E cig users for research of E cig effects on human healthand allow investigators to uncover potential detrimental and beneficial effects related to E cigs