Evaluation of potential for toxicity from subacute inhalation of tire and road wear particles in rats

Figures & data

Table 1.  International ambient air standards for particulate matter.

Country	Particle size	Duration	Standard (µg/m^3)
United States	PM10	24-h	150
	PM2.5	Annual	15
	PM2.5	24-h	35
European Union	PM10	Annual	40
	PM10	24-h	50
	PM2.5	Annual	25
Canada	TSP	Annual	60
Japan	PM2.5	Annual	15
	PM2.5	24-h	35

Figure 1.  Diagram of exposure system.

Table 2.  Measured air concentration and average particle size for TRWP by exposure level.

Target concentration (µg/m^3)	Measured concentration (SD) (µg/m^3)	NMAD (GSD) (µm)	MMAD (GSD) (µm)	% Mass <3 µm
100	112.2 (29.7)	1.29 (1.60)	3.68 (1.83)	45.7
40	37.8 (19.1)	1.13 (1.56)	3.04 (1.80)	56.6
10	12.5 (10.5)	1.04 (1.46)	2.38 (1.81)	71.0

MMAD, mass median aerodynamic diameter; NMAD, number-median aerodynamic diameter; TRWP, tire and road wear particles.

Figure 2.  Particle size distributions of tire and road wear particles (TRWP) used for animal exposure. (A) Representative histogram of mass median aerodynamic diameter (MMAD) particle size distribution of the 100 µg/m³ exposure group; (B) representative histogram of number-median aerodynamic diameter (NMAD) particle size distribution of the 100 µg/m³ exposure group.

Figure 3.  Body weight data for duration of study. Data are presented as mean ± SE (n = 5 per treatment group). *Represents day of sacrifice; body weight recording started in advance of study initiation.

Figure 4.  Cell differential profile in lavage fluid with tire and road wear particles (TRWP) exposure. Data are presented as mean ± SE. n = 10 per treatment group (males and females combined).

Figure 5.  Inflammatory cytokine expression in lavage fluid with tire and road wear particles (TRWP) exposure. Data are presented as mean ± SE. n = 10 per treatment group (males and females combined). (A) interleukin-6 (IL-6); (B) growth-related oncogene-keratinocyte chemoattractant (GRO-KC); (C) tumor necrosis factor-α (TNF-α).

Figure 6.  Markers of cytotoxicity in lavage fluid in response to tire and road wear particles (TRWP) exposure. Data are presented as mean ± SE. n = 10 per treatment group (males and females combined). (A) Total protein; (B) lactate dehydrogenase (LDH) activity; (C) alkaline phosphatase (ALP) activity.

Figure 7.  Histopathology of tire and road wear particles (TRWP) exposure. (A) Low power magnification of focal area of subacute inflammation in the lung. The perimeter is outlined by arrows to demonstrate the limited focal extent of minimal alteration. (B) Higher power magnification to illustrate infiltration of low numbers of mononuclear inflammatory cells interstitial in the thickened interalveolar wall and in alveolar spaces (asterisks) with few neutrophils (thin arrows). Hyperplasia of acinar lining epithelial cells indicated pneumocyte regeneration (thick arrows).

Figure 8.  Sample results from comparative toxicity study: Intratracheal instillation. Data are presented as mean ± SE. n = 8 per treatment group (males and females combined). *Statistically different from air control; ^#Statistically different from vehicle control; ^†Statistically different from tire and road wear particles (TRWP) (1 mg). ^‡Statistically different from tread particles (TPs) (1 mg).