Bridging in vitro and human studiesPublished on 04.05.2026
Predicting human lung responses to solvents
Everyday cleaning and painting products may be quietly straining our lungs, new research from Unisanté, the Lausanne University Center for Primary Care and Public Health, and the Adolphe Merkle Institute (AMI) suggests.
This study also highlights the potential of in vitro–to–in vivo extrapolation (IVIVE) approaches to predict real-world risk in risk assessment, while supporting the 3Rs principle of replacing, reducing, and refining animal use.
The team at Unisanté showed, using a group of 11 volunteers, that brief, low-concentration inhalation of two common organic solvents ubiquitous in paints, inks, and cleaning products – propylene glycol monomethyl ether (PGME) and propylene glycol butyl ether (PGBE) – can temporarily reduce the amount of oxygen reaching the blood in healthy individuals. These results indicate that early and rapid effect markers can be identified in healthy participants following low-concentration exposure.
To uncover the underlying mechanism, researchers from AMI's BioNanomaterials group exposed sophisticated 3D human lung cell models to controlled doses of the same solvents. They found that PGBE, in particular, reduced the permeability of the lung tissue barrier. At very high concentrations, both PGME and PGBE damaged cells and made the barrier leaky, with PGBE proving about four times more toxic than PGME in standard viability tests.
The AMI team also observed a slight change in the lung cell surface tension at relatively high doses, suggesting that the solvents may disrupt the thin protective layer, - the pulmonary surfactant- that helps keep alveoli, the tiny air sacs in the lungs, open. Even minor increases in surface tension can make alveoli more prone to collapse, further reducing the surface available for oxygen uptake.
The doses used in the human study were below the level a worker might be exposed to over an eight-hour shift, based on the current occupational exposure limit (OEL) for PGME. No OEL exists for PGBE, which is probably more toxic than PGME. The results highlight the need for further research on the pulmonary effects of short- and long-term exposure to propylene glycol ethers, including among workers and vulnerable groups, to prevent the development of lung conditions.
Controlled human studies, performed at low exposure doses, in combination with in vitro experiments using toxic concentrations, are crucial steps in translating findings from controlled cellular experiments into actual biological systems such as humans. This study can be used to predict human inhalation risk and to set limits for PGEs, bridging the gap between controlled cellular studies and human biological outcomes.
A controlled human study
Eleven healthy volunteers were exposed in a whole-body inhalation chamber for 4 hours to either ambient air or low concentrations of PGME and PGBE, levels below those a worker might be exposed to over an eight-hour shift.
During solvent exposure, the arterial partial pressure of oxygen decreased, and deoxygenated hemoglobin increased. Although the participants did not feel any effects (non-clinical effects), the parameters were sufficiently sensitive to distinguish solvent exposure from ambient air.
The researchers also observed subtle changes in white blood cell counts and haptoglobin levels, a protein linked to lung tissue stress, suggesting a mild inflammatory response.
All parameters remained within the clinical range and returned to baseline after exposure, indicating that these changes were exposure-related and reversible at the concentrations tested.
Reference: He, R.; Pache, J.; Hopf, N. B.; Rothen-Rutishauser, B.; Petri-Fink, A.; Wild, P.; Borgatta, M. Pulmonary Effects of Inhalation Exposure to Propylene Glycol Ethers on Blood Gas Diffusion – a Human and in Vitro Study. Environment International 2025, 205, 109888. https://doi.org/10.1016/j.envint.2025.109888.
