| Epidemiological studies have demonstrated an association between increased levels of ambient particulate matter (PM) air pollution and excess daily morbidity and mortality. Many of these studies indicate that individuals with cardiopulmonary disease may be at particular risk to adverse PM health effects. It has been proposed that soluble transition metals complexed to the surface of PM are responsible for many of the reported adverse health effects. To examine the roles of transition metals in causing PM toxicity, studies of residual oil fly ash (ROFA), a PM sample with a relatively high soluble metal composition, were conducted in conscious, unrestrained rats. Rats were implanted with radiotelemetry transmitters to continuously monitor heart rate (HR), core temperature (T CO), and electrocardiographic data throughout the exposure. Intratracheally-instilled ROFA induced both immediate and delayed responses in rats, consisting of hypothermia, bradycardia, and arrhythmogenesis; these responses were exacerbated in animal models of cardiopulmonary stress and disease. Further investigation of ROFA-associated transition metals showed that instilled vanadium (V) caused the immediate response, while instillation of nickel (Ni) caused the delayed effect. Futhermore, Ni potentiated the immediate effects caused by V, while iron (Fe) attenuated the toxicity of instilled V and Ni+V. The results of these instillation studies were then further tested by exposing rats to aerosolized metals in a whole-body exposure chamber. Due to the uncertainty of uptake and ventilation parameters in dose estimation models, four exposure concentrations, ranging from 0.3–2.1 mg/m3, were used to model the total dose from instillations. Animals were exposed to Ni, V, and Ni+V at these levels for 6 hours per day x 4 days. At the highest concentration, V failed to induce any observable change in HR or TCO. Ni caused delayed hypothermia, bradycardia, and arrhythmogenesis at 1.3 and 2.1 mg/m3. When combined, Ni and V produced observable delayed effects at 0.5 mg/m3, and more severe toxicity at 1.3 mg/m3 than that produced by 2.1 mg/m3 of Ni alone. The results of these studies suggest that metals play a major role in ROFA toxicity; Ni appears to cause the greatest toxicity when inhaled. Furthermore, these data indicate a synergism between inhaled Ni and V, and a possible attentuating interaction by Fe. |
