An in vitro comparison of the toxicological profiles of ground tire particles (TP) and actual tire and road wear particles (TRWP) emissions.

There is currently limited data on the potential effects of tire and road wear particles (TRWP) on human health. TRWP include tire fragments, but also road wear materials, dust, adsorbed gaseous pollutants and different types of inclusions that could affect their hazard profiles. Due to their availability and lower complexity, ground tire particles (TP) are often used in toxicological studies. However, this makes it difficult to draw firm conclusions about the potential hazard of actual TRWP. Here, we compared the in vitro toxicological profile of ground TP and actual TRWP emissions of similar size collected from road traffic. For this purpose, TP and TRWP were separately incubated with alveolar macrophages for 24 h, and the cellular response was evaluated in terms of cytotoxicity, proinflammatory response and oxidative stress. Both TP and TRWP induced neither significant cytotoxicity nor oxidative stress, but triggered a concentration-dependent proinflammatory response, as evidenced by increased TNF-α production. The level of TNF-α production was slightly higher with TRWP than with TP, independent of the particle dose. All in all, the pulmonary toxicity of TRWP could be due primarily to the tire tread inclusions and only marginally to other particle components (i.e. road wear materials, dust …). Although these preliminary results need to be confirmed by further analysis, they could be useful for tire manufacturers in the production of safer-by-design tires.

Biological effects of Tire and Road Wear Particles (TRWP) assessed by in vitro and in vivo studies - A systematic review.

Air quality is a critical issue because even small amounts of air pollutants can cause significant adverse health effects. Road traffic is a major contributor to air pollution both through aerosols from exhaust emissions (EE) and non-exhaust emissions (NEE). The latter result from mechanical abrasion of brakes and tires, erosion of road surfaces and resuspension of road dust into the atmosphere by passing traffic. EE have been extensively characterized and have declined over time due to mitigation measures. By contrast, NEE have been less studied, are not tightly regulated and there are limited data on their toxicity. Thus, NEE relative part has become prevalent, potentially making of these emissions a major human health concern. The aim of this systematic review was to provide an overview of the current state of knowledge on the biological effects of NEE. We paid particular attention to the toxicological effects of Tire and Road Wear Particles (TRWP) induced in vitro and in vivo in mammalian models. To this end, we performed a bibliographic search in two databases (PubMed and Web of Science). Of the 400 papers, 22 were found to be relevant and included in our analysis, confirming that the assessment of the TRWP toxicity in mammalian models is still limited. This review also reports that oxidative stress and inflammation are the main mechanisms underlying the toxicity of TRWP.

The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2.

Keratinocytes (KC) play a crucial role in epidermal barrier function, notably through their metabolic activity and the detection of danger signals. Chemical sensitizers are known to activate the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), leading to cellular detoxification and suppressed proinflammatory cytokines such as IL-1ß, a key cytokine in skin allergy. We investigated the role of Nrf2 in the control of the proinflammatory response in human KC following treatment with Cinnamaldehyde (CinA), a well-known skin sensitizer. We used the well-described human KC cell line KERTr exposed to CinA. Our results showed that 250 µM of CinA did not induce any Nrf2 accumulation but increased the expression of proinflammatory cytokines. In contrast, 100 µM of CinA induced a rapid accumulation of Nrf2, inhibited IL-1ß transcription, and downregulated the zymosan-induced proinflammatory response. Moreover, Nrf2 knockdown KERTr cells (KERTr ko) showed an increase in proinflammatory cytokines. Since the inhibition of Nrf2 has been shown to alter cellular metabolism, we performed metabolomic and seahorse analyses. The results showed a decrease in mitochondrial metabolism following KERTr ko exposure to CinA 100 µM. In conclusion, the fate of Nrf2 controls proinflammatory cytokine production in KCs that could be linked to its capacity to preserve mitochondrial metabolism upon chemical sensitizer exposure.