Sub-chronic inhalation toxicity study of a smelting by-product in the rat

抄録

The objective of this 90-day study was to obtain information on the toxicity of a smelting by-product when administered to Wistar (Han) rats via the inhalation route for at least 90 days (6 hours/day, 5 days/week), with the aim of evaluating any toxic effects, without death or suffering, and verification of clearance mechanisms.

The animals were exposed to the test atmosphere at concentrations of 0.3, 0.1 and 0.03 mg/L (High, Mid and Low Dose), using a nose-only exposure system. Control animals were exposed to filtered air. The Mass Median Aerodynamic Diameter (MMAD) was 2.41±2.09 µm to 2.65±2.02 µm and considered respirable by rodents.

The exposure to the test item resulted in increased lung weights in the test item exposed animals in a dose dependent manner, when compared with controls.

Microscopically, test item-related changes were seen in the lung as diffuse pigmented macrophages or free pigments in the alveoli; pigment in the bronchus associated lymphoid tissue (BALT); and minimal to slight multifocal alveolar epithelial hyperplasia. Pigment was also seen in the mediastinal lymph nodes of animals exposed to the test item, with multifocal eosinophilic globules (droplets) observed in the respiratory and/or olfactory epithelium of the nasal cavity.

In conclusion, changes seen in this study were considered to be non-adverse physiological responses or secondary responses to the inhaled test item. In the lung, macrophages loaded with a black pigment were considered to be a result of a normal physiological response to phagocytose and remove the inhaled test item.