Pulmonary response to toner upon chronic inhalation exposure in rats

A chronic inhalation study of a test toner was conducted by exposure of groups of F-344 rats for 6 hr/day, 5 days/week for 24 months. The test toner was a special Xerox 9000 type xerographic toner, enriched in respirable-sized particles compared to commercial toner, such that it was about 35% respirable according to the ACGIH criteria. The target test aerosol exposure concentrations were 0, 1.0 (low), 4.0 (medium), and 16.0 (high) mg/m3. Titanium dioxide (5 mg/m3) and crystalline silicon dioxide (1 mg/m3), used as negative and positive controls for fibrogenicity, were also evaluated. Inhalation of the test toner or the control materials showed no signs of overt toxicity. Body weight, clinical chemistry values, food consumption, and organ weights were normal in the toner- and TiO2-exposed groups, except for a 40% increase in lung weight in the toner high-exposure group. All of the changes in the toner-exposed groups were restricted to the lungs or associated lymph nodes. A chronic inflammatory response was evident from the bronchoalveolar lavage parameters for the toner high-exposure group. The incidence of primary lung tumors was comparable among the three toner-exposed groups and the TiO2-exposed, and air-only controls, as well as consistent with historical background levels. A mild to moderate degree of lung fibrosis was observed in 92% of the rats in the toner high-exposure group, and a minimal to mild degree of fibrosis was noted in 22% of the animals in the toner middle-exposure group. The pulmonary changes in the toner high-exposure group were smaller in magnitude than those found in the crystalline silica-exposed group. The comparative fibrogenic potency of TiO2, toner, and SiO2 was estimated to be 1:5:418 using a dosimetric model and assuming a common mechanistic basis. There were no pulmonary changes of any type at the toner low-exposure level, which is most relevant in regard to potential human exposures. The lung alterations in the toner high-exposure group are interpreted in terms of "lung overloading," a generic response of the respiratory system to saturation of its detoxification capacity. The maximum tolerated dose (MTD) criterion was met at the toner high (16 mg/m3)-exposure level.