A Case Study for the Comparison of In Vitro Data Across Multiple Aerosol Exposure Studies with Extrapolation to Human Dose

April 5, 2018

DOI: 10.1089/aivt.2017.0042

David Thorne, Emma Bishop, Linsey Haswell, and Marianna Gaca
British American Tobacco Group R&D, Southampton, United Kingdom

This case study has demonstrated that dosimetry techniques using particulate markers can allow in vitro biological data generated on five independent aerosol exposure system studies, under contrasting experimental designs and with different cell types, to be directly compared.

In vitro aerosol systems offer advantages in generating aerosols and exposing cell cultures at the air–liquid interface (ALI), mimicking human exposure. However, dilution technologies, principles, and characteristics of exposure chambers differ between systems. In addition, various cell types and biological end points can be assessed, meaning that in vitro aerosol data are presented in different ways, so researchers are unable to compare data between systems, studies, and laboratories. In this case study we present the comparison of in vitro data across multiple aerosol exposure studies using a 3R4F reference tobacco product. The first aim assessed whether a consistent in vitro dosimetry approach could gain insight into the characterization of ALI aerosol exposure systems. The second aim assessed whether cytotoxicity data sets generated on contrasting exposure systems with different experimental setups could be directly compared. Cytotoxicity data generated from five independent studies were compared. When plotted on the x-axis as a function of dilution principle, the ‘‘standard way’’ to present whole aerosol data, there was little read across between the data sets. Expressing each data set as a function of particulate dose (µg/cm2) and nicotine concentration (mg), however, allowed comparisons between all data sets and with human daily exposure estimates. Furthermore, compared as a function of dose, the data set showed remarkable commonalities between themselves despite clear study differences. The data demonstrate that in vitro dosimetry techniques can align data between contrasting setups and experimental protocols to facilitate comparisons and provide a link between in vitro, in vivo, and human dosimetry studies.

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