Abstract
The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled TiO2 particles that have been substantially encapsulated with pyrogenically deposited, amorphous silica. Groups of rats were intratracheally instilled either with doses of 1 or 5 mg/kg of hydrophilic Pigment A TiO2 particles or doses of 1 or 5 mg/kg of the following control or particle-types: 1) R-100 TiO2 particles (hydrophilic in nature); 2) quartz particles, 3) carbonyl iron particles. Phosphate-buffered saline (PBS) instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24 hrs, 1 week, 1 month and 3 months.The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to Pigment A or R-100 TiO2 particles produced transient inflammatory and cell injury effects at 24 hours postexposure (pe), but these effects were not sustained when compared to quartz-related effects. Exposures to carbonyl iron particles or PBS resulted only in minor, short-term and reversible lung inflammation, likely related to the effects of the instillation procedure.Histopathological analyses of lung tissues revealed that pulmonary exposures to Pigment A TiO2 particles produced minor inflammation at 24 hours postexposure and these effects were not significantly different from exposures to R-100 or carbonyl iron particles. Pigment A-exposed lung tissue sections appeared normal at 1 and 3 months postexposure. In contrast, pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy (lipid-containing) alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis.Based on our results, we conclude the following: 1) Pulmonary instillation exposures to Pigment A TiO2 particles at 5 mg/kg produced a transient lung inflammatory response which was not different from the lung response to R-100 TiO2 particles or carbonyl iron particles; 2) the response to Pigment A was substantially less active in terms of inflammation, cytotoxicity, and fibrogenic effects than the positive control particle-type, quartz particles. Thus, based on the findings of this study, we would expect that inhaled Pigment A TiO2 particles would have a low risk potential for producing adverse pulmonary health effects.
Highlights
This study was designed as a preliminary screen to determine whether Pigment A TiO2 particles (TiO2 particles that have been substantially encapsulated with pyrogenically deposited, amorphous silica) impart significant toxicity in the lungs of rats, and more importantly, how the activity of this TiO2 formulation compares with other reference particulate materials
The aim was to assess in rats, using a well-developed, short-term pulmonary bioassay the acute pulmonary toxicity effects of intratracheally instilled, Pigment A TiO2 particle samples and to compare the lung toxicity of these samples with 2 low toxicity particulate-types and a cytotoxic particulate sample; and 2) to bridge the results of these instillation studies with data previously generated from inhalation studies with quartz particles in the form of crystalline silica and with carbonyl iron particles as the inhalation/instillation bridge materials
The pulmonary toxicity of instilled Pigment A TiO2 particles was compared with a positive control particletype, quartz, as well as two negative control particle-types, carbonyl iron particles and R-100 TiO2 particles
Summary
This study was designed as a preliminary screen to determine whether Pigment A TiO2 particles (TiO2 particles that have been substantially encapsulated with pyrogenically deposited, amorphous silica) impart significant toxicity in the lungs of rats, and more importantly, how the activity of this TiO2 formulation compares with other reference particulate materials. The aim was to assess in rats, using a well-developed, short-term pulmonary bioassay the acute pulmonary toxicity effects of intratracheally instilled, Pigment A TiO2 particle samples and to compare the lung toxicity of these samples with 2 low toxicity particulate-types (negative controls) and a cytotoxic particulate (positive control) sample; and 2) to bridge the results of these instillation studies with data previously generated from inhalation studies with quartz particles in the form of crystalline silica and with carbonyl iron particles as the inhalation/instillation bridge materials
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