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Particle and Fibre Toxicology

, 2:2

First Online: 24 March 2005Received: 26 November 2004Accepted: 24 March 2005

Abstract

BackgroundThis 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 μm 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.

ResultsThe 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.

ConclusionThe 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.

List of abbreviationsANOVAanalysis of variance

ALPalkalin phosphatase

BALFbronchoalveolar lavage fluid

BALTbronchoalveolar lymphoid tissue

BrdU5-bromo-2-deoxyuridine

b.w.body weight

CC16Clara cell protein

EHC-93urban PM sample, Ottawa dust

ELISAenzyme-linked immunosorbent assay

ET-1endothelin-1

GSHreduced glutathione

GSSGoxidized glutathione

HEhematoxylin-eosin

HIA- Hendrik-Ido-Ambacht

HVCIhigh volume cascade impactor

IL-6interleukin-6

LDHlactate dehydrogenase

MIP-2macrophage inflammatory protein-2

MPOmyeloperoxidase

Mφmacrophages

NAGN-acetyl glucosaminidase

ODoptical density

PMparticulate matter

PBSphosphate buffered saline

PBSTPBS with 10 mM 0.1% Tween 20

PMNspolymorphonuclear neutrophils

PUFpolyurethane foam

ROFAresidual oil fly ash

RTDroad tunnel dust

s.c.subcutaneous

SEMstandard error of the mean

SHspontaneously hypertensive

TNF-αtumor necrosis factor α

UAuric acid

vWFvon Willebrand factor

Electronic supplementary materialThe online version of this article doi:10.1186-1743-8977-2-2 contains supplementary material, which is available to authorized users.

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Autor: Miriam E Gerlofs-Nijland - A John F Boere - Daan LAC Leseman - Jan AMA Dormans - Thomas Sandström - Raimo O Salonen -

Fuente: https://link.springer.com/







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