Road traffic is a significant source of urban particulate matter (PM), with diesel exhaust emissions being a key concern. Non-exhaust emissions, particularly brake wear, are an increasing concern, but very little is known about their effects. The study reveals that brake-wear PM, especially from ceramic and non-asbestos organic (NAO) brake pads, is more toxic to cellular health than diesel exhaust PM. This toxicity is associated with copper in the brake pads, which may lead to conditions such as Alzheimer’s disease, cardiovascular disease, cancer, and chronic obstructive pulmonary disease (COPD).
Oxidative stress, an important mechanism for PM toxicity, results in cellular damage and deoxyribonucleic acid (DNA) damage, which leads to inflammation and cell death. Brake-wear PM from NAO and ceramic pads emits more reactive oxygen species (ROS) and generates greater oxidative stress than diesel PM. These emissions are specific to the brake pads and more toxic than diesel exhaust.
The inflammation induced by brake-wear PM can result in lung function impairment and multi-organ toxicity. In this study, NAO and ceramic brake-wear PM induced the release of pro-inflammatory markers with a major contribution from copper. Furthermore, brake-wear PM stimulated the expression of metallothioneins, the proteins that maintain zinc and copper homeostasis within cells. This effect was particularly pronounced in the case of NAO brake-wear PM, which had higher levels of copper.
Brake-wear copper is a heavy source of air pollution, and it is associated with respiratory diseases and lowered lung function. Previous studies indicated that there exists a definite linkage between exposure to copper and breathing complications. These results confirm that copper accumulates in cells and causes toxicity in brake-wear PM.
Non-exhaust emissions are not adequately controlled by legislation currently, so there are not many technologies available to limit their release. Non-exhaust emissions are also more chemically diverse than exhaust emissions, which means they have varying impacts on health based on their source. This emphasizes the need to learn about how non-exhaust emissions, particularly from brake wear, impact us.
Researchers employed an interdisciplinary strategy to examine the impact of brake-wear fine particles with a diameter of <2.5 ÎĽm (PM 2.5) on lung alveolar cellular homeostasis associated with that of diesel exhaust particles. This involved employing ribonucleic acid (RNA) sequencing to observe changes in total gene expression and metabolic assays to investigate alterations in glycolytic reprogramming, mass spectrometry to describe the composition of the particles, and reporter assays to assist in explaining the varying effects observed.
The research examined the impact of various forms of brake-wear PM from four brake pad types (LowM, SemiMxCu, NAO, and ceramic) and diesel exhaust PM on alveolar type-II epithelial cells (ATII). The major findings are:
The study analyzed PM 2.5–0.1 (aerodynamic diameter 2.5–0.1 ÎĽm) from automobile brake-wear PM produced from four types of pads (low-metallic, LowM; semi-metallic with controlled copper, SemiMxCu; non-asbestos organic, NAO; and ceramic), employing diesel exhaust PM 2.5–0.1 as a reference.Â
To explore the biological effects of each PM type, we initially treated an alveolar type-II epithelial cell line (ATII) with PM in concentrations up to 32 µg/cm² for 24 h and examined for cytotoxicity determined by lactate dehydrogenase (LDH) release. The cytotoxicity increased in a concentration-dependent manner following treatment with PM 2.5–0.1 from NAO and ceramic brake wear, as well as diesel PM at 32 µg/cm².
NAO and ceramic brake-wear PM induced the most significant increase in ROS production, with no impact from LowM or diesel PM. Gene expression analysis revealed higher levels of oxidative stress-related genes (Heme oxygenase 1 [HMOX1] and glutamate-cysteine ligase modifier subunit [GCLM]) following exposure to NAO and ceramic PM.
NAO and ceramic brake-wear PM elicited the largest number of gene expression changes, at 2212 and 2153 differentially expressed genes, respectively, over the other PM types. Upregulation of ROS and hypoxia-related pathways was amongst these changes, along with glycolytic shift. Seahorse analysis proved that the metabolic shift was by detecting increased glycolysis.
To examine the effect of NAO brake-wear PM on FIH activity, a GAL4-UAS reporter system was employed. Factors inhibiting hypoxia-inducible factor (FIH) inhibition were elevated with increased luciferase activity. Exposure to NAO brake-wear PM elevated luciferase activity further, reflecting FIH inhibition. Hypoxia response element (HRE) assay indicated that NAO brake-wear PM promoted the binding of HIF1α to HREs, which amplified hypoxia-inducible gene expression.Â
In addition, exposure to NAO brake-wear PM stabilized the levels of hypoxia-inducible factor 1α (HIF) protein, and this effect was diminished by ascorbate and inhibited by the copper-selective chelator tetraethylenepentamine (TEPA). These findings imply that copper-loaded PM initiates the HIF pathway through oxidative stress and inactivation of FIH. Statistical significance reported was found to be p ≤ 0.05, p ≤ 0.01, p ≤ 0.001, and p ≤ 0.0001 in all cases.
Researchers have found that brake-wear particles (PM) may have a greater impact on cell balance than diesel exhaust particles. The data signify that not all vehicle road-particle types affect health in the same manner, particularly in comparing exhaust and non-exhaust particles or even distinct non-exhaust particle types. This suggests further insights into the possible health effects of air pollution. These results emphasize the importance of the composition of these particles in influencing health, and they indicate the necessity of laws aimed at protecting public health.
Reference: Parkin JGH, Dean LSN, Bell JA, et al. Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis. Part Fibre Toxicol. 2025;22(4). doi:10.1186/s12989-024-00617-2
