Inflammatory Impacts of Tire-Related Particles: Do All Roads Lead to Rome?

Details

• Personal Author:
  Wehle, B. ; Li, Y. ; Monge, C. ; Razazan, Atefeh ; Murugesan, V. ; Friend, Sherri A. ; Kodali, Vamsi K. ; Driesschaert, B. ; Hussain, Salik
• Description:
  Background and Purpose: Current air pollution regulations focus entirely on exhaust emissions. However, inhalation of tire wear particles (TWP), produced when tires are worn down in contact with the road surface, could pose an emerging threat to human health. The environmental burden of TWP is expected to increase in coming years as more consumers transition to heavier electric vehicles that produce greater TWP emissions compared to conventional vehicles. TWP are composed of a unique chemical cocktail, including antioxidants like N-(1,3-Dimethylbutyl)-N'-phenylp- phenylenediamine, or 6PPD, which can be converted to toxic quinones under environmental conditions, impacting the toxicity of these particles with time. TWP have demonstrated toxicity to several species of freshwater fish, yet understanding of their impact on human health is still rudimentary. This study investigates the inflammatory effects of tire wear particle exposure in C57BL/6 wild-type mice and NLRX1- knockout mice. NLRX1 is a modulator of inflammation, often contributing to the control of inflammation initiation and preventing an overactive immune response. We predicted that exposure to TWP will elicit a pulmonary inflammatory response, with a more pronounced response occurring in the NLRX1-KO mice. Methods: TWP from commercial passenger vehicle tires were prepared by either grinding or cryomilling. Physical characteristics and chemical composition were assessed via scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and high-performance liquid chromatography (HPLC). We additionally evaluated the potential of particles to generate oxidants/free radicals using electron paramagnetic resonance (EPR). 9-12-week-old male and female C57BL/6 wild type and NLRX1 knockout mice were used for this study. Mice were exposed via intratracheal instillation to 1 mg/ Kg body weight TWP suspension. 24 hours after treatment, mice were euthanized and bronchoalveolar lavage (BAL) was performed on the left lung while the right lung was collected. Total cell counts and differential cell counting were performed on the bronchoalveolar lavage fluid. RNA was extracted from the right lung for real-time PCR analysis of inflammatory cytokine expression, including the cytokines KC, TNF-a, IL-6, IL-10, and STAT3. Results: SEM of TWP demonstrated a wide range of sizes (100 nm - 80 micron) and EDS demonstrated a complex elemental composition including Fe, Cu, Zn, S, Si, O, C and Cr. We validated the method for the extraction of 6PPD and 6PPD-Q from TWP using HPLC coupled with mass spectrometry. EPR analyses demonstrated significantly elevated oxidant levels in the BAL fluid. Moreover, BAL fluid from mice exposed to TWP exhibited an increase in the total number of cells, macrophages, and neutrophils. NLRX1-KO mice demonstrated significantly greater neutrophil recruitment in lavage compared to WT mice. Increased KC, TNF-a, and IL-6 gene and protein expression was observed after TWP exposure. Conclusions: In sum, we demonstrate that TWP have a complex composition and elicit a pulmonary inflammatory response depending on their composition and genotype of the mice. Further studies are underway to determine the mechanistic pathways implicated in the inflammatory response and to clarify the relative contribution of different components of TWP in their pulmonary toxicity. Description provided by NIOSH
• Subjects:
  • Immune System
  • Inflammation
  • Motor Vehicles
  • Occupational Health
  • Respiratory System
  • Safety
• Keywords:
  • Environmental impacts; Motor vehicles; Motor vehicle parts; Immune reaction; Laboratory animals; Pulmonary effects; Toxicology
• Source:
  Toxicologist 2025 Mar; 204(S1):483
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Philadelphia Region OSHA ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  2 pdf pages
• Volume:
  204
• NIOSHTIC Number:
  nn:20071587
• Federal Fiscal Year:
  2025
• Peer Reviewed:
  False
• Download URL:
  https://stacks.cdc.gov/view/cdc/259362/cdc_259362_DS1.pdf
• File Type:
  [PDF - 260.62 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:113674385f435bdbc9247a5ae4bcdd572f3fa68d02be7e669245aa719975af0f6d0ddbf5f542b08808f004eeb6db0db07dd6f8afa6aaba63c0a1d2cf4d781b24