Mj. Reasor et Jm. Antonini, Pulmonary responses to single versus multiple intratracheal instillations of silica in rats, J TOX E H A, 62(1), 2000, pp. 9-21
Citations number
19
Categorie Soggetti
Environment/Ecology,"Pharmacology & Toxicology
Journal title
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A
The pulmonary toxicity of particles is often studied using a single intratr
acheal instillation of the material. It was hypothesized that smaller multi
ple intratracheal administrations of silica would result in differences in
pulmonary responses as compared to a single large intratracheal administrat
ion. In the first of a series of experiments, the pulmonary responses in ma
le 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 fro
m 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 salin
e intratracheally. In the second experiment, the dose was reduced to 1 mg/1
00 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 experiment
s, 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 bronchoal
veolar lavage, which is an index of inflammation, and the level of albumin
in the bronchoalveolar lavage fluid, a measure of damage to the capillary-e
pithelial barrier. At the higher dose of silica, similar levels of inflamma
tion and lung damage were evident in both dosing protocols. Less severe res
ponses occurred at the lower dose. The comparative pattern between the sing
le and multiple dosing protocols was similar in all three experiments. Sinc
e only minor differences were noted in the pulmonary responses when the res
ponses to the single- and multiple-dose protocols were compared, data indic
ate that the multiple-dose protocol does not offer any advantages over the
single- dose protocol.