Human and Rat Biological Differences Highlight Need for Human-Relevant Inhalation Toxicity Testing

A new paper, out today in Regulatory Toxicology and Pharmacology and coauthored by PETA Science Consortium International e.V., the US Environmental Protection Agency, the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, and other collaborators, demonstrates how interspecies differences in humans and rats limit the ability of rat inhalation tests to predict what will happen when humans inhale a substance. While inhalation toxicity testing to date has often been conducted using rats, this paper shows the value of instead using non-animal testing approaches grounded in human biology and mechanisms of toxicity.

The review, “Differences in the anatomy and physiology of the human and rat respiratory tracts and impact on toxicological assessments,” examines breathing modes, airway structures, and other key differences in the micro- and macroscopic anatomies and physiologies of humans and rats that may impact the ability of inhalation tests using rats to predict human outcomes.  

The paper opens the doorway for harnessing modern toxicology tools and our understanding of the human respiratory tract to inform the development of non-animal testing approaches grounded in human biology. It is also a reminder that, due to key differences in the respiratory tracts of rats and humans, data from human-cell-based, non-animal approaches should not necessarily be expected to align with or be directly compared to data from tests on rats.