Pulmonary responses to single versus multiple intratracheal instillations of silica in rats.
Toxicologist 1999 Mar; 48(1-S):132
The pulmonary toxicity of particles is often studied using a single intratracheal (I.T.) instillation of the material. Criticism has been levied that this procedure is not representative of inhalation exposure. In this study, we compared the pulmonary responses in male F344 rats to a single I.T. instillation of crystalline silica (5 mg/IOO gm BWt) given on day 0 with those resulting from 5 consecutive daily I.T. instillations of the dust (1 mg/100 gm BWt per day) with the initial dose given on day 0. Controls received the sterile saline vehicle I.T.. The multiple instillation protocol was used as an experimental surrogate for inhalation exposure. The total amount of silica instilled was the same in the two protocols. Responses were assessed on day 14. The indices of response were cellular differentials recovered by bronchoalveolar lavage (BAL) and the level of albumin in BAL fluid (BALF). With both instillation protocols, the total cells, PMNs, and lymphocytes recovered and albumin levels in BALF were increased significantly in the silica-treated rats versus the respective controls. There were no significant differences between the single and multiple instillation protocols for any of these values for either controls or silica-treated rats. Therefore, at this high dose of silica, where particle overload may be occurring, the single and multiple instillation protocols gave similar pulmonary responses using these endpoints. Responses at other doses of silica and the use of additional endpoints are being investigated.
Animal-studies; Laboratory-animals; Statistical-analysis; Analytical-methods; Analytical-chemistry; Exposure-assessment; Toxicology; Toxins; Toxic-materials; Pulmonary-system-disorders; Pulmonary-disorders; Respiratory-system-disorders; Respiratory-irritants; Particulate-dust; Particulates; Dust-exposure; Dust-inhalation; Dust-particles; Airborne-dusts; Airborne-fibers; Airborne-particles; Silica-dusts; Silicates
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana