There are increasing concerns about animals being used to assess the toxicity of substances and consumer products such as tobacco products. For example, Directive 2010/63/EU encourages organizations to replace animal testing with new approach methodologies (NAMs) intended to reduce, refine, or replace (3R) in vivo animal testing methods traditionally used for toxicity testing and risk assessment.

NAMs are emerging safety assessment tools consisting of in vitro and in silico (computational) methodologies. NAM tools are expanding however, they are not necessarily all “new”, but it is mainly their application beyond hazard toxicity testing, enabling NAM-based regulatory decision making without the use of new animal testing that would be new. While NAMs are often associated with in vitro testing using human cells or tissues and establishing adverse outcome pathways (AOPs) for human disease outcomes, they also include less established tools of quantitatively correlating in vitro findings against human exposures (i.e., in vitro-to-in vivo extrapolation, IVIVE) that are crucial in modernizing risk assessment and ultimately removing the need for traditional in vivo testing.

The aim of this Research Topic is to showcase NAM-based toxicological risk assessment for next generation tobacco and nicotine products (NGPs) for the purpose of product screening/testing and pre-market regulatory submission. NGPs, viewed as potentially reduced risk products compared to combustible cigarettes, include a variety of tobacco and nicotine products and in this issue, we focus on inhalable NGPs that are gaining traction in markets (e.g., heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS)).

NAMs topics to consider include, but are not limited to:
· Human cell-based in vitro assays (e.g., cell-free systems, cell culture systems, ALI, organ-on a-chip, etc.) to evaluate toxicity and predict human health risks
· Mode-of-Action (MoA) to connect early events in toxicity adverse outcome pathways (AOPs) for clinically relevant disease outcomes
· Case examples of how NAMs are used for NGP toxicological risk assessment, beyond screening or hazard characterization
· In vitro-to-in vivo extrapolation (IVIVE), exposure dosimetry
· In vitro-based risk assessment for components and whole products
· NAM-based toxicity (absolute and relative) profiles of NGPs
· Case examples of NAMs standardization or fit-for-purpose qualification and validations

Different Article Types can be submitted to the Research Topic including Original Research, Review, Mini-Review, Brief Research Report, Perspective articles, among others.

Topic Editor Ranulfo Lemus is employed by the International Tungsten Industry Association and is founder and director of LeTox World LLC. Topic Editor Monica Lee is self-employed as a toxicological consultant. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

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