On-Road Animal Inhalation Studies


Elder, A., J-P. Couderc, R. Gelein, S. Eberly, C. Cox, X. Xia, W. Zareba, P. Hopke, W. Watts, D. Kittelson, M. Frampton, M. Utell, and G. Oberdörster. 2007.

Effects of On-Road Highway Aerosol Exposures on Autonomic Responses in Aged, Spontaneously Hypertensive Rats.

Inhalation Toxicology. 19(1):1-12. Link To Paper

Abstract

     Epidemiological studies associate ambient particulate pollution with adverse health outcomes in elderly individuals with cardiopulmonary diseases. We hypothesized that freshly generated ultrafine particles (UFP) contribute to these effects, as they are present in high number concentrations on highways and vehicle passengers are exposed directly to them. Aged spontaneously hypertensive rats (9-12 mo) with implanted radiotelemetry devices were exposed to highway aerosol or filtered, gas-denuded (clean) air using an on-road exposure system to examine effects on heart rate (HR) and heart-rate variability (HRV). On the day of exposure, rats were pretreated with low-dose inhaled or injected lipopolysaccharide (LPS) to simulate respiratory tract or systemic inflammation, respectively.
     Exposures (6 h) in compartmentalized whole-body chambers were performed in an air conditioned compartment of a mobile laboratory on I-90 between Rochester and Buffalo, NY. HRV parameters were calculated from telemetric blood pressure signals and analyzed for the baseline period and for the first 32 h postexposure. The aerosol size (count median diameter=15-20 nm; geometric standard deviation=1.4-4.3) and number concentration (1.95-5.62×105/cm3) indicated the predominance of UFP. Intraperitoneal LPS significantly affected all of the parameters in a time-dependent manner; response patterns after inhaled or injected LPS pretreatment were similar, but more prolonged and greater in LPS-injected rats. A significant effect of highway aerosol was found, irrespective of pretreatment, which resulted in decreased HR in comparison to clean air-exposed rats. This effect was more persistent (?14 h) in those rats that received ip LPS as compared to saline. The highway aerosol also significantly affected short-term alterations in autonomic control of HR, as evidenced by elevations in normalized high frequency power and decreased vagosympathetic balance. These findings show that environmental exposure concentrations of mixed traffic-related UFP/gas-phase emissions can affect the autonomic nervous system.


Kittelson, D. B., W. F. Watts, J. P. Johnson, M. L. Remerowki, E. E. Ische, G. Oberdörster, R. M. Gelein, A. C. Elder, P. K. Hopke, E. Kim, W. Zhao, L. Zhou, and C.-H. Jeong. 2004.

On-Road Exposure to Highway Aerosols 1. Aerosol and Gas Measurements.

Inhal. Toxicol. 16(suppl. 1):31-39. Link to Paper

Abstract

     On-road experiments were conducted to determine the sensitivities of rats to real-world aerosol. This paper summarizes the on-road aerosol and gas measurements and provides background information for the companion paper on the rat exposures. Measurements were carried out over 10 days, six hours each day, driving a route from Rochester to Buffalo.
     Aerosol instrumentation used in this study included two scanning mobility particle sizers (SMPS) to determine the aerosol size distribution from 10 to 300 nm, two stand-alone condensation particle counters to determine the total aerosol number concentration and an electrical aerosol detector to determine the aerosol length concentration. A thermal denuder (TD) was used with one of the SMPS instruments to determine the size distribution of the non-volatile fraction. Filter samples were collected and analyzed for elemental carbon, and gas analyzers measured ambient levels of CO, CO2      Average daily total aerosol number concentration ranged from 200,000 to 540,000 particles/cm3. Past studies on urban highways have measured total number concentrations ranging between 104 and 106 particles/cm3. The average daily NO concentration ranged from 0.10 to 0.24 ppm and the corresponding CO2 concentration ranged from 400 to 420 ppm. The average daily geometric number mean particle size determined by the SMPS ranged from 15 to 20 nm. The TD reduced the average SMPS number concentration between 87 and 95 % and the SMPS volume between 54 and 83 %, suggesting that most of the particles consisted of volatile material. The TD also increased the geometric number mean diameter from 15 to 20 nm to 30 to 40 nm.


Elder, A. C. P., R. Gelein, J. Finkelstein, R. Phipps, M. Frampton, M. Utell, D. B. Kittelson, W. F. Watts, P. Hopke, C. Jeong, W. Liu, W. Zhao, L. Zhuo, R. Vincent, P. Kumarathasan, and G. Oberdörster. 2004.

On-Road Exposure to Highway Aerosols 2. Exposures of Aged, Compromised Rats.

Inhal. Toxicol. 16(suppl. 1):41-53. Link to Paper

Abstract

      Ambient particulate pollution is associated with adverse health effects in epidemiological studies of the elderly with cardiopulmonary diseases. We hypothesize that ultrafine particles (UFP) contribute to these effects, especially when they are freshly generated and occur at high number concentrations. Studies to determine adverse effects have been performed using laboratory generated surrogates, diluted exhaust from stationary engines, or concentrated ambient UFPs. Methodological difficulties exist with such experiments, and questions remain about how well these particles model those found in ambient air. Freshly generated UFPs are present at high concentrations on highways and vehicle passengers are directly exposed to them. We wished to expose rats to these UFPs to test their potential to cause effects. Since such exposures have not been done before, one objective of our study was to demonstrate the feasibility of an on-road exposure study. Secondly, we wished to determine if there are significant exposure-related effects in aged, compromised rats. Old rats (21-mo F-344) were exposed directly on highways to either the aerosol (<1 ?m)/gas phase, gas phase only, or filtered air using an on-road exposure system.
      Some rats were pretreated with a low dose of inhaled endotoxin or with instilled influenza virus to induce lung inflammation. The exposures in compartmentalized whole-body chambers consisted of 6-h driving periods on I-90 between Rochester and Buffalo once or 3 days in a row. Endpoints related to lung inflammation, inflammatory cell activation, and acute-phase responses were measured after exposure. The on-road exposure system did not affect measured endpoints in filtered air-exposed rats, indicating that it was well tolerated by them. We observed the expected increases in response (inflammation, inflammatory cell activation) to the priming agents. We also found a significant particle-associated increase in plasma endothelin-2, suggesting alterations in vascular endothelial cell activation. In addition, we observed main effects of particles related to the acute-phase response and inflammatory-cell activation. Interactions between on-road particles and the priming agents were also found. These results suggest that exposures to on-road particle mixtures have effects on the pulmonary and cardiovascular system in compromised, old rats. Furthermore, they demonstrate that on-road exposures are feasible and could be performed in future studies with more continuous particle exposures.


CDR Home


Last modified: 29 January 2009