UNIVERSITY OF ROCHESTER – EPA PM Center Assessment of Ambient UFP Health Effects : Linking Sources to Exposure and Responses in Extrapulmonary Organs

tentative) The focus of the Rochester PM Center studies was an assessment of our ultrafine particle (UFP) hypothesis that states that exposure of susceptible members of the population to UF mode particles (<100 nm, PM0.1) in the urban atmosphere can cause adverse health effects. Some key findings of our studies from measurements of ambient particles, from conducting epidemiological cohort studies, and using surrogate UFP in controlled clinical studies, toxicological animal studies and in vitro studies confirmed that ambient UF/fine particles: — Contain reactive oxygen species (ROS); — Can be measured in real-time with an Aerosol Time-of-Flight Mass Spectrometer (ATOFMS) down to particle sizes of 50 nm and in random mode down to 10 nm; — Show substantial increases in the organic carbon content when concentrated in an UFP concentrator when compared with the ambient particles; — Are associated with changes in vascular parameters indicative of an acute phase response, increased coagulation activation and adhesion molecule expression in patients with coronary heart disease; — Are associated with onset of myocardial infarction 1 hr after exposure to traffic, according to time activity diaries; — Induce changes in vascular parameters (acute phase response) and ECG (parasympathic stimulation) in rats following on-road exposure to highway PM; — Induce changes in cardiac function represented by HRV, repolarization parameters and supraventricular and ventricular ectopic beats in patients with coronary heart disease as well as changes in HRV in patients with COPD; and that inhaled laboratory-generated carbon UFP: — Have a high deposition efficiency in the respiratory tract, which is further increased in asthmatics and during exercise; — Translocate to extrapulmonary organs via the blood circulation, dependent on particle chemistry, and to the central nervous system, via olfactory neurons; — Cause changes in adhesion molecule expression of peripheral blood leukocytes, indicative of pulmonary vascular effects in healthy and asthmatic humans; — Alter ischemia-induced hyperemic blood flow in healthy subjects, indicative of particle effects on systemic endothelial function; — Decrease the pulmonary diffusing capacity for carbon monoxide in healthy humans; — Accelerate venous thrombus formation in rats; — Induce greater oxidative stress in lungs of aged rats compared to adolescent rats and that ozone co-exposure can increase this response; and — Demonstrate greater sensitivity to UFP-induced oxidative stress in the aged organism as is evident in in vitro primary cell cultures in alveolar macrophages from aged rats.