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Pulmonary responses to single versus multiple intratracheal instillations of silica in rats.

Authors
Reasor-MJ; Antonini-JM
Source
J Toxicol Environ Health, A 2001 Jan; 62(1):9-21
NIOSHTIC No.
20020790
Abstract
The pulmonary toxicity of particles is often studied using a single intratracheal instillation of the material. It was hypothesized that smaller multiple intratracheal administrations of silica would result in differences in pulmonary responses as compared to a single large intratracheal administration. In the first of a series of experiments, the pulmonary responses in male F344 rats to a single intratracheal instillation of crystalline silica (5 mg/100 g body weight) given on d 0 were compared with those resulting from 5 consecutive daily intratracheal administrations of the dust (1 mg/100 g body weight/d) with the initial dose given on d 0. Controls received saline intratracheally. In the second experiment, the dose was reduced to 1 mg/100 g body weight for the single-dose protocol and 0.2 mg/100 g body weight/d for 5 consecutive days for the multiple-dose protocol. In both experiments, responses were assessed on d 14. In the third experiment, the doses were the same as the first experiment, but the responses were assessed on d 28. The indices of toxicity were cellular differentials recovered by bronchoalveolar lavage, which is an index of inflammation, and the level of albumin in the bronchoalveolar lavage fluid, a measure of damage to the capillary-epithelial barrier. At the higher dose of silica, similar levels of inflammation and lung damage were evident in both dosing protocols. Less severe responses occurred at the lower dose. The comparative pattern between the single and multiple dosing protocols was similar in all three experiments. Since only minor differences were noted in the pulmonary responses when the responses to the single- and multiple-dose protocols were compared, data indicate that the multiple-dose protocol does not offer any advantages over the single-dose protocol.
Keywords
Pulmonary-system; Silica-dusts; Animal-studies; Laboratory-animals; Lung-function
Contact
Mark J. Reasor, PhD, Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center of West Virginia University, PO Box 9223, Morgantown, WV 26505-9223, USA
CODEN
JTEHD6
Publication Date
20010112
Document Type
Journal Article
Email Address
mreasor@hsc.wvu.edu
Editors
Kacew-S
Fiscal Year
2001
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0098-4108
NIOSH Division
HELD
Priority Area
Pulmonary System Disorders; Surveillance Research Methods
Source Name
Journal of Toxicology and Environmental Health, Part A: Current Issues
State
WV
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