title: Inhalation toxicity study of disk-shaped potassium  octatitanate particles (terracess TF) in rats following  90 days of aerosol exposure.
abstract: Since fibrous particles such as asbestos and some man-made fibers (MMF) have been known to produce carcinogenic or fibrogenic effects, disk-shaped potassium octatitanate (POT) particles (trade name: Terracess TF) were manufactured as nonfibrous particles. A 90-day inhalation toxicity study of Terracess TF was performed to evaluate comparative inhalation toxicity of the disk shape with a fibrous shape that was previously evaluated. Four groups of 20 male and 15 female rats each were exposed to Terracess TF aerosols at concentrations of 0, 2, 10, or 50 mg/m(3) for 90 days. Ten male and 10 female rats per group were sacrificed at 90 days of exposure. After 90 days of exposure, 5 male rats per group were sacrificed at 3 wk of recovery period and 4-5 male rats per group or 5 female rats per group were sacrificed at 15 wk of recovery for lung clearance and histopathology. The mass median aerodynamic equivalent diameter (MMAED) of the aerosols of test materials ranged from 2.5 to 2.9 microm. There were no test-substance-related adverse effects on clinical observations. At the end of the 90-day exposure, a slight increase in lung-to-body weight ratios was observed at 50 mg/m(3) in male but not in female rats. However, lung weights were within normal limits after 3- or 15-wk recovery periods. Microscopically, inhaled Terracess TF particles were mostly phagocytized by free alveolar macrophages (AMs) in the alveolar airspaces and alveolar walls maintained normal structure at 2 and 10 mg/m(3). At 50 mg/m(3), some alveoli were distended and filled with aggregates of particle-laden AMs. The alveolar walls showed slight type II pneumocyte hyperplasia, but neither proliferative inflammation nor alveolar fibrosis was present at 50 mg/m(3). The clearance half-times for Terracess TF were estimated to be in the order of 6 to 9 mo for the 50-mg/m(3) group and 2 to 3 mo for the 10- and 2-mg/m(3) groups. The lung responses and lung clearance rate were comparable to those of "nuisance" type dusts at these concentrations. Based on interpretation that aggregated particle-laden AMs in alveoli was considered to be an early histopathological sign of lung overloading, an effect level was considered to be 50 mg/m(3) and no-observedadverse- effect level (NOAEL) was 10 mg/m(3). This experiment clearly demonstrated that particle morphology was considered to be an important factor to determine inhaled particle toxicity.
authors.affiliation: Otsuka Chemical Co., Ltd., Osaka, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Sakai
authors.forename: Kousuke
authors.initials: K
authors.lastname: Inada
authors.forename: Akira K
authors.initials: AK
authors.lastname: Tanaka
authors.forename: David P
authors.initials: DP
authors.lastname: Kelly
authors.forename: Greg P
authors.initials: GP
authors.lastname: Sykes
authors.forename: K P
authors.initials: KP
authors.lastname: Lee
mesh_terms: D000336:Aerosols; D000818:Animals; D005260:Female; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate; D008903:Minerals / Q000493:pharmacokinetics / Q000633:toxicity*; D009929:Organ Size; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020127:Recovery of Function; D014025:Titanium / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000336:Aerosols; D008903:Minerals; C021028:potassium octatitanate; D014025:Titanium