Pulmonary toxicity studies in rats with triethoxyoctylsilane (OTES)-coated, pigment-grade titanium dioxide particles: bridging studies to predict inhalation hazard.
The aim of this study was to assess and compare the acute lung toxicities of intratracheally instilled hydrophobic relative to hydrophilic surface-coated titanium dioxide (TiO(2)) particles using a pulmonary bridging methodology. In addition, the results of these instillation studies were bridged with data previously generated from inhalation studies with hydrophilic, pigment-grade (base) TiO(2) particles, using the base, pigment-grade TiO(2) particles as the inhalation/instillation bridge material. To conduct toxicity comparisons, the surface coatings of base pigment-grade TiO(2) particles were made hydrophobic by application of triethoxyoctylsilane (OTES), a commercial product used in plastics applications. For the bioassay experimental design, rats were intratracheally instilled with 2 or 10 mg/kg of the following TiO(2) particle-types: (1) base (hydrophilic) TiO(2) particles; (2) TiO(2) with OTES surface coating; (3) base TiO(2) with Tween 80; or (4) OTES TiO(2) with Tween 80. Saline instilled rats served as controls. Following exposures, the lungs of sham- and TiO(2)-exposed rats were assessed both using bronchoalveolar lavage (BAL) biomarkers and by histopathology of lung tissue at 24 hours, 1 week, 1 month, and 3 months post exposure. The results demonstrated that only the base, high-dose (10 mg/kg) pigment-grade TiO(2) particles and those with particle-types containing Tween 80 produced a transient pulmonary inflammatory response, and this was reversible within 1 week postexposure. The authors conclude that the OTES hydrophobic coating on the pigment-grade TiO(2) particle does not cause significant pulmonary toxicity.
DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714, USA. david.b.warheit@usa.dupont.com
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Warheit
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Reed
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Webb
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure / Q000009:adverse effects*; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010860:Pigments, Biological / Q000008:administration & dosage / Q000633:toxicity*; D011136:Polysorbates; D051381:Rats; D011919:Rats, Inbred Strains; D020127:Recovery of Function; D012828:Silicones / Q000737:chemistry; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*; D023382:Toxicity Tests, Acute
D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D010860:Pigments, Biological; D011136:Polysorbates; D012828:Silicones; C009495:titanium dioxide; D014025:Titanium