The perpetuation of the misconception that rats receive a 3-5 times lower lung tissue dose than humans at the same...

This paper highlights the pervasive misconception concerning 1994 findings from Hatch et al. about ozone (O₃) tissue dose in humans versus rats. That study exposed humans to 0.4 ppm and rats to 2 ppm ¹⁸O-labeled O₃ and found comparable incorporation of ¹⁸O into bronchoalveolar lavage constituents. However, during O₃ exposure humans were exercising, which increased their ventilation rate five-fold, while rats were at rest. This resulted in similar O₃ tissue doses between the two species, and predominantly explained the comparable ¹⁸O incorporation at five-fold different concentrations. The five-times higher exercising human inhalation rate offset the five-times lower concentration, producing the same human dose expected at rest at 2 ppm (i.e. 0.4 ppm × 4686 L/2 hour ≈ 2 ppm × 998 L/2 hour). In 2013, Hatch et al. showed that resting humans and resting rats experienced fairly comparable ¹⁸O incorporation at the same O₃ exposure concentration and activity state into BALF cells. Despite these findings, we show here that in the peer-reviewed literature a substantial proportion of researchers continue to perpetuate the misunderstanding that human lung tissue doses of O₃ are simply 3-5 times greater than rat doses at the same O₃ concentration, due to interspecies differences, and not considering activity state. It is important to correct this misconception to ensure an appropriate understanding of the implications of O₃ studies by the scientific community and policy experts making regulatory decisions (e.g. the US Environmental Protection Agency's National Ambient Air Quality Standards for O₃).