title: Effects of particulate matter on the pulmonary and vascular system: time course in spontaneously hypertensive rats.
abstract: BACKGROUND: This study was performed within the scope of two multi-center European Commission-funded projects (HEPMEAP and PAMCHAR) concerning source-composition-toxicity relationship for particulate matter (PM) sampled in Europe. The present study aimed to optimize the design for PM in vivo toxicity screening studies in terms of dose and time between a single exposure and the determination of the biological responses in a rat model mimicking human disease resulting in susceptibility to ambient PM. Dust in thoracic PM size-range (aerodynamic diameter <10 mum) was sampled nearby a road tunnel (RTD) using a high volume cascade impactor. Spontaneously hypertensive rats were exposed to urban dust collected in Ottawa, Canada (EHC-93 10 mg/kg of body weight; reference PM) or different RTD doses (0.3, 1, 3, 10 mg/kg of body weight) by intratracheal instillation. Necropsy was performed at 4, 24, or 48 hr after exposure. RESULTS: The neutrophil numbers in bronchoalveolar lavage fluid increased tremendously after exposure to the highest RTD doses or EHC-93. Furthermore, PM exposure slightly affected blood coagulation since there was a small but significant increase in the plasma fibrinogen levels (factor 1.2). Pulmonary inflammation and oxidative stress as well as changes in blood coagulation factors and circulating blood cell populations were observed within the range of 3 to 10 mg PM/kg of body weight without significant pulmonary injury. CONCLUSION: The optimal dose for determining the toxicity ranking of ambient derived PM samples in spontaneously hypertensive rats is suggested to be between 3 and 10 mg PM/kg of body weight under the conditions used in the present study. At a lower dose only some inflammatory effects were detected, which will probably be too few to be able to discriminate between PM samples while a completely different response pattern was observed with the highest dose. In addition to the dose, a 24-hr interval from exposure to sacrifice seemed appropriate to assess the relative toxic potency of PM since the majority of the health effects were observed one day after PM exposure compared to the other times examined. The aforementioned considerations provide a good basis for conducting PM toxicity screening studies in spontaneously hypertensive rats.
authors.affiliation: National Institute for Public Health and the Environment (RIVM), P,O, Box 1, 3720 BA, Bilthoven, The Netherlands. miriam.gerlofs@rivm.nl.
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Gerlofs-Nijland
authors.forename: A John F
authors.initials: AJ
authors.lastname: Boere
authors.forename: Daan Lac
authors.initials: DL
authors.lastname: Leseman
authors.forename: Jan Ama
authors.initials: JA
authors.lastname: Dormans
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandström
authors.forename: Raimo O
authors.initials: RO
authors.lastname: Salonen
authors.forename: Leendert
authors.initials: L
authors.lastname: van Bree
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee