Imperial Brands studies link lower toxicants to reduced biological activity

Laboratory analysis reveals a direct correlation between combustion-related toxicant levels and cellular stress responses, according to two recent investigations by Imperial Brands researchers. The findings, published in Mutagenesis and the Journal of Applied Toxicology, indicate that next generation products (NGP) exhibit substantially lower biological activity compared to cigarette smoke.

Assay results on cellular stress pathways

The first study employed ToxTracker and ToxProfiler assays to detect oxidative stress, DNA damage, and protein stress across various product extracts. Researchers compared a reference cigarette against aerosols from heated tobacco, heated herbal products, and two vape devices. Cigarette smoke consistently triggered the strongest biological responses in both assay systems.

In contrast, the heated tobacco product showed markedly reduced activity, while the heated herbal variant displayed only limited signs of oxidative stress. Neither vape product activated any measured cellular stress pathways. The data classified cigarette smoke as genotoxic under test conditions, whereas no NGP extracts received this classification. These biological outcomes closely mirrored the underlying chemistry, with lower toxicant levels corresponding to reduced biological impact.

Human cell-based model comparisons

A second investigation utilized high-content screening to assess how respiratory and cardiovascular human cells respond to different aerosols. This approach examined whether chemical emission reductions translate into similar effects within sophisticated biological models. Once again, cigarette smoke produced the most intense biological reactions.

Heated tobacco aerosols resulted in diminished activity, while vape aerosols demonstrated either significantly lower responses or no measurable effects. The study confirmed a clear relationship between chemistry and biology, reinforcing the finding that products with fewer combustion-related toxicants generate less cellular stress. Oxidative stress emerged as a key mechanism driving many of the observed responses, offering deeper insight into how smoke and aerosols interact with biological systems.

Weight-of-evidence and New Approach Methodologies

Neither single study can fully characterize the complex biological effects of these products. Instead, the combined evidence supports a weight-of-evidence approach, where independent techniques provide mutually reinforcing conclusions. Whether using reporter-gene assays or advanced human-cell screening, the pattern remained consistent: cigarette smoke caused the highest biological response, heated products showed substantial reduction, and vapes exhibited the lowest activity.

Matthew Stevenson, Scientific Substantiation Senior Manager and lead author, stated that the studies highlight the growing importance of New Approach Methodologies (NAMs). These animal-free techniques allow scientists to investigate not just whether a biological response occurs, but also the mechanisms driving it. The research demonstrates how multiple scientific disciplines can build a broader understanding of product performance through complementary toxicological approaches.