A tiered approach to investigate the inhalation toxicity of cobalt substances. Tier 4: Effects from a 28-day inhalation toxicity study with tricobalt tetraoxide in rats

Lung cancer following inhalation in rodents is a major concern regarding exposure to cobalt substances. However, little information is available on adverse effects and toxicity following long-term inhalation exposure to poorly soluble cobalt substances with low bioavailability. Thus, the present study focused on pulmonary effects of the poorly soluble tricobalt tetraoxide (5, 20, 80 mg/m³) in a 28-day inhalation exposure study. Lung weights increased with increasing exposures. Bronchoalveolar lavage fluid analysis and histopathology revealed lung tissue inflammation at the mid-dose with increasing severity in the high-dose group and post-exposure persistency. Markers for cellular damage and cell proliferation were statistically significantly increased. No increase in 8-OH-dG lesions was observed, indicating an absence of oxidative DNA lesions. The primary effect of inhaled Co3O4 particles is inflammation of the respiratory tract strongly resembling responses of inhaled “inert dust” substances, with a NOAEC of 5 mg/m³ under the conditions of this test.