Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide.

The inhalation toxicity of asbestos (1332214) and titanium-dioxide (13463677) mixtures was studied in rats. AF-rats were exposed to respirable dusts containing 10mg/m3 chrysotile (12001295) or amosite (12172735), plus 10mg/m3 titanium-dioxide for 1 year. They were maintained for lifespan observation. Selected rats were killed at the end of exposure and at 6 months post exposure and the lungs were removed. The left lung was analyzed for asbestos and titanium-dioxide. The right lung was analyzed for histopathological changes. At the end of exposure deposits of asbestos and titanium-dioxide were found in lesions containing macrophages, giant cells, and fibroblast containing collagenous fibers. These lesions were more pronounced in rats examined 6 months after exposure ended. Pulmonary fibrosis occupying 9.5 to 12.9% of the lung parenchyma was observed. The extent and severity of fibrosis induced by asbestos was not increased by titanium-dioxide. Rats exposed to chrysotile plus titanium-dioxide had a significantly increased incidence of pulmonary tumors compared to those exposed to chrysotile only. A similar nonsignificant trend was seen for rats exposed to amosite plus titanium-dioxide. The lung burdens of chrysotile or amosite in rats simultaneously exposed to titanium-dioxide were significantly increased relative to those exposed to chrysotile or amosite only. The authors conclude that inhalation of titanium-dioxide, a particulate dust normally considered to be innocuous, may enhance the carcinogenicity of amosite and chrysotile. This may reflect increased pulmonary retention of chrysotile and amosite in animals exposed to titanium-dioxide.