Poster, SOT 65th Annual Meeting and ToxExpo, March 22–25, 2026, in San Diego, California.
Michael J. Oldham1; Kei Yoshino2; Marianna Gaca3; Liam Simms4; Yuki Kanemaru5; Utkarsh Doshi6; Roman Wieczorek4; Ito Shigeaki2; Hiromi Ohara2; Ali A. Rostami6; Ali Salehi6; Amy K. Madl7; Michael Hollings8; Srikar Dudi4; Jingjie Zhang6; Arkadiusz K. Kuczaj9; Brian Keyser10; Robert Leverette10; Stanlezy Gilliland III11; Amit Gupta12; Aditya R. Kolli9; Ramez Labib12; Francesco Lucci9; Konstantinos Papikinos4; Todor Antonijevico13; Marjory Moreau13,14
1. Juul Labs, Inc.; 2. Japan Tobacco Inc.; 3. BAT (Investments) Ltd; 4. Imperial Brands; 5. JTI SA; 6. Altria Client Services LLC; 7. Valeo Sciences LLC; 8. Labcorp; 9. Phillip Morris Products S.A.; 10. RAI Services Company; 11. Sapphire Sciences; 12. Battelle; 13. ScitoVation, LLC.; 14. Currently at ESQLabs
Introduction
In the evaluation of Next-Generation Products (NGPs), the meaningfulness of in vitro toxicology depends strongly on how closely laboratory doses mirror human reality. A comprehensive collaborative study from Oldham and colleagues provides a vital foundation for this alignment by defining clinically relevant exposure doses for Electronic Nicotine Delivery Systems (ENDS) and Heated Tobacco Products (HTP).
By utilizing Physiologically Based Pharmacokinetic (PBPK) modeling and reverse dosimetry, researchers successfully translated human plasma nicotine levels into precise tissue-level exposure metrics (µg or ng/cm²-min). This approach allows for the characterization of nicotine deposition across different regions of the respiratory tract with high resolution.
The findings highlight a significant discrepancy in current research: many standard in vitro protocols apply doses that are orders of magnitude higher than those experienced by actual users. Establishing these clinically relevant dose ranges provides a scientifically robust basis for future in vitro studies, ensuring that laboratory findings are directly applicable to real-world human exposure scenarios.
