Our new toxicological studies provide fresh insight into the assessment of next generation products
Two newly published studies from Imperial Brands scientists have provided further evidence that products associated with lower levels of combustion-related toxicants also produce substantially lower biological activity than cigarette smoke under laboratory conditions.
Published respectively in Mutagenesis and the Journal of Applied Toxicology, the studies used different but complementary toxicological approaches to investigate how a range of next generation products (NGP) compare with cigarettes. Despite employing distinct methodologies, both studies arrived at remarkably consistent conclusions.
Together, the findings demonstrate how multiple scientific disciplines can be used to build a broader understanding of product performance through a cumulative weight-of-evidence approach.
Multiple Scientific Methods, Consistent Findings
The first study utilised the ToxTracker and ToxProfiler assays, advanced laboratory techniques capable of detecting cellular stress responses associated with oxidative stress, DNA damage, protein stress, and other biological pathways.
Researchers compared extracts from a reference cigarette with aerosols from a heated tobacco product, a heated herbal product, and two vape products. Across both assay systems, cigarette smoke consistently produced the strongest biological responses.
In contrast, the heated tobacco product generated substantially reduced activity, the heated herbal product produced only limited signs of oxidative stress, and neither vape activated any of the cellular stress pathways measured during the study.
Importantly, the biological findings closely reflected the underlying chemistry. Products containing lower levels of combustion-related toxicants also produced lower levels of biological activity.
The study further classified cigarette smoke as genotoxic under the test conditions used, whereas none of the NGP extracts were classified as genotoxic.
Looking Beyond Traditional Toxicology
The second study explored a complementary scientific question: whether reductions in harmful chemical emissions are similarly reflected within more sophisticated human cell-based biological models.
Using advanced high-content screening approaches, researchers examined how cells from both the respiratory system and cardiovascular system responded following exposure to cigarette smoke and NGP aerosols.
Once again, cigarette smoke consistently produced the strongest biological responses.
The heated tobacco aerosol produced reduced activity, while the vape aerosols demonstrated either considerably lower responses or no measurable effects under the conditions tested.
As with the ToxTracker investigation, a clear relationship emerged between chemistry and biology. Products with lower levels of combustion-related toxicants consistently generated lower biological activity within the cellular systems assessed.
Researchers also demonstrated that oxidative stress appears to play an important role in many of the observed responses, providing additional mechanistic insight into how smoke and aerosols interact with biological systems.
Building Confidence Through a Weight-of-Evidence Approach
No single study can fully characterise the biological effects of complex products such as cigarettes or NGP.
This is why modern product assessment increasingly relies on complementary scientific disciplines.
However, these latest studies demonstrate how independent assessment techniques can provide mutually reinforcing evidence.
Whether using reporter-gene assays like ToxTracker and ToxProfiler, or advanced human-cell high-content screening approaches, the overall pattern remained consistent:
Supporting the Evolution of Modern Toxicology
The studies also highlight the growing importance of New Approach Methodologies (NAMs) in product assessment.
These advanced, animal-free techniques allow scientists to investigate not simply whether a biological response occurs, but also the mechanisms that may be driving it.
Matthew Stevenson, Scientific Substantiation Senior Manager and lead author of the Mutagenesis study, commented:
“One of the most encouraging aspects of this research programme was seeing different scientific methods arrive at such consistent conclusions. As levels of combustion-related toxicants decreased, so too did the biological responses observed across a variety of laboratory systems.”
Edgar Trelles Sticken, Biology and Toxicology Laboratory Team Lead and co-author of the Journal of Applied Toxicology study, added:
“No single study provides all the answers. However, when multiple complementary approaches consistently point in the same direction, confidence in the overall conclusions grows. Together, these studies demonstrate the value of a multidisciplinary, weight-of-evidence approach to modern product assessment.”
Kostas Papikinos, Senior Product Stewardship Toxicologist and co-author, concluded:
“Advanced, animal-free assessment methods are helping scientists build a more detailed understanding of how products interact with biological systems. These approaches provide important mechanistic insights and continue to strengthen the evidence base supporting science-led stewardship and tobacco harm reduction.”
Read more about our approach to in-vitro science and NAMs here.
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