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CONTROLLED DIESEL EXPOSURES: INTER-PHASING HUMAN AND ANIMAL STUDIES AND THEIR USE IN THE RISK ASSESSMENT
Citation:
Madden, M. C. CONTROLLED DIESEL EXPOSURES: INTER-PHASING HUMAN AND ANIMAL STUDIES AND THEIR USE IN THE RISK ASSESSMENT. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
Controlled diesel exposures: Inter-phasing human and animal studies and their use in the risk assessment process.
Michael C. Madden, US EPA.
Particulate matter (PM) has been reported to be associated with health effects (e.g., premature deaths, hospitalizations, lung cancer), and gaseous components may influence the PM-induced effects. Diesel exhaust (DE) contributes to ambient PM and gaseous compounds, but the role that DE plays in PM-induced effects is not well established. Controlled exposure studies using human volunteers and animal models can confirm the role DE may play in PM toxicity; also the removal of a DE component (e.g., particles) may reveal whether the removed component is involved in the observed response(s). A limited number of acute, controlled exposure studies of human volunteers administered either whole DE or individual components by inhalation or instillation have been used to examine nasal and lung responses including indices of inflammation and allergy. More numerous acute exposures of nonhuman animal models have revealed similar pulmonary alterations, and have better linked lung responses to the composition of particles. Further acute exposure investigations with animal models have revealed DE-induced cardiovascular changes (hypertension, arrhythmias). Chronic exposure regimens have also been utilized with rodents to examine the carcinogenicity of DE. Exposures in vitro have been also utilized with cells from target organ systems in order to assess relative potencies of DE and DE constituents (e.g., organic solvent-extractable), potential mechanisms that operate in vivo (e.g., signal transduction), and other possible responses not widely examined in vivo. In combination with key human studies, animal and cell in vitro models have begun to elucidate the possible biological responses induced by DE exposure, determined bioactive component(s), better established dose-response relationships, and identified possible susceptible populations. Findings from these studies assist in the assessment of risk from DE in different exposure scenarios, and ultimately in the management of health risks from DE exposure. [This abstract may not represent official EPA policy.]