Pulmonary response to toner, TiO2 and crystalline silica upon chronic inhalation exposure in Syrian golden hamsters

A chronic inhalation study of a test toner, TiO(2), and crystalline silica was conducted by exposure of groups of Syrian golden hamsters (strain: Han:AURA) for 6 h/day, 5 days/wk for 18 mo. Subsequently, the animals inhaled clean air only for an additional period of 5 mo. The target test aerosol exposure concentrations were 1.5, 6, and 24 mg/m(3) for the test toner, 40 mg/m(3) for TiO(2), and 3 mg/m(3) for SiO(2). The latter two materials were used as negative and positive controls for fibrogenicity. The aerosol concentrations were changed to 4, 16, and 64 mg/m(3) for toner (referred to as loner low, toner medium, and toner high) and 30 mg/m(3) for TiO(2) after 5 mo, in order to achieve the desired lung burdens. Inhalation of the test loner or the control materials showed no signs of overt toxicity. Body weight, hematology and clinical chemistry values, food consumption, and organ weights were normal in the toner-, TiO(2)(-), and SiO(2)-exposed groups, except for relative lung weights with elevations of up to 56%, 98%, and 98% for the loner high, the TiO(2), and the SiO(2) group at the end of the study. Small increases in the number of segmented neutrophils and decreases in the mean percentage of lymphocytes were observed in the same groups, indicating a mild inflammatory reaction in the lung. All of the changes in the loner-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-, the TiO(2)(-), and the SiO(2)-exposed groups. Primary lung tumors were not found in the control or toner-exposed groups. One small-sized bronchioloalveolar adenoma was observed in a female of the TiO(2)(- )exposed group and one in a female of the SiO(2)-exposed group. A very slight to slight degree of interstitial fibrosis was observed after exposure to toner medium (in 49% of hamsters), to toner high (83%), to TiO(2) (82%), and SiO(2) (91%). Two squamous-cell carcinomas of the forestomach were observed in the male toner high group as well as in the female SiO(2) group. Upon closer examination, an increased incidence of forestomach papillomas was detected in all particle-exposed groups, but there was no dose-response relationship among the three toner-exposed groups. Several of the observed lesions randomly distributed in most of the exposure groups, such as the neuroendocrine tumors (larynx and trachea), heart thrombosis, and forestomach papilloma(s), are not considered to be relevant for human risk assessment. The maximum tolerated dose (MTD) criterion was exceeded at the toner high and the TiO(2) exposure concentrations. The results of the present investigation coupled with the previously documented chronic inhalation studies in rats lead to the firm conclusion that inhalation of toner does not represent a carcinogenic hazard.