Detection of 6-PPD and 6-PPDQ in airborne particulates and assessment of their toxicity in lung cells.

The extensive use of synthetic antioxidants, notably N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6-PPD), in rubber-related products, particularly in tire manufacturing, has induced concerns regarding their environmental impact and potential health hazards. Despite the identification of 6-PPD and its derivative, 6-PPD quinone (6-PPDQ), in various water samples and their lethal effects on certain aquatic species (e.g., coho salmon, rainbow trout and brook trout), the levels of airborne 6-PPD/6-PPDQ and their respiratory toxicity remain relatively unexplored. In this study, we aimed to evaluate the respiratory toxicity potential of 6-PPD and its derivatives, with a specific focus on detecting these compounds in airborne particulates and assessing their toxic effects on lung cells. Characterization of four airborne fine particulate (FP) samples revealed spherical morphologies with diameters ranging from 17.7 to 225.7 nm, displaying slight agglomeration and negative surface charge. methanol/acetonitrile extraction followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis confirmed the presence of both 6-PPD and 6-PPDQ on the surfaces of FPs, with significant variations (0.26-1.05 μg g) in loading capacity observed among the samples. Subsequent exposure of lung cells (THP-1, BEAS-2B, and A549) to 6-PPD and 6-PPDQ revealed dose-dependent declines in mitochondrial metabolic activity induced by 6-PPD, along with severe membrane damage, ATP depletion, and pro-inflammatory cytokine release. Conversely, 6-PPDQ exhibited negligible toxicity in all tested parameters. These findings underscore the potential health risks associated with airborne 6-PPD exposure and emphasize the importance of further research into the respiratory toxicity of 6-PPD derivatives.