Hexavalent chromium responsible for lung lesions induced by intratracheal instillation of chromium fumes in rats.

Lung toxicity of chromium fumes (Cr fumes) was examined by a single intratracheal instillation into rats of 10.6 mg and 21.3 mg Cr fumes/kg body weight and by repeated (3 times) instillations of 10.8 mg and 21.7 mg Cr fumes/kg. The pathological changes were compared with those induced by single administrations of 3.2 mg and 19.2 mg Na2CO3 solution-insoluble fraction of Cr fumes (Cr-Fr)/kg and 20.8 mg commercially available chromium (III) oxide powder (Cr (III) oxide)/kg. Single and repeated administrations of Cr fumes suppressed growth rate in a dose-dependent manner, but administrations of Cr-Fr and Cr (III) oxide did not. A single administration of Cr fumes produced granulomas in the entire airways and alveoli with progressive fibrotic changes, as well as severe mobilization and destruction of macrophages and foamy cells. Those histopathological changes were aggravated by the repeated administration of Cr fumes. On the other hand, single administrations of Cr-Fr and Cr (III) oxide produced no remarkable histopathological changes. Cr fumes were found to be composed of 73.5% chromium (III) oxide and 26.5% chromium (VI) oxide. The primary particles of Cr fumes and Cr-Fr were similar, 0.02 micron in size (sigma g: 1.25), and Cr (III) oxide particles were 0.30 micron in size (sigma g: 1.53), measured by analytical electron microscopy (ATEM). Diffuse clusters of the primary particles in Cr fumes were identified as Cr (VI) oxide. The present results suggested that the lung toxicity of Cr fumes was mainly caused by these Cr (VI) oxide (CrO3) particles in Cr fumes.