title: Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management.
abstract: The development of a risk management system for nanoscale or ultrafine particle-types requires a base set of hazard data. Assessing risk is a function of hazard and exposure data. Previously, we have suggested "parallel tracks" as a strategy for conducting nanoparticle research. On the one hand, mechanistic studies on "representative" nanoparticles could be supported by governmental agencies. Alternatively, with regard to commercial nanoparticles, the environmental, health and safety (EHS) framework would include a minimum base set of toxicity studies which should be supported by the companies that are developing nano-based products. The minimum base set could include the following criteria: substantial particle characterization, pulmonary toxicity studies, acute dermal toxicity and sensitization studies, acute oral and ocular toxicity studies, along with screening type genotoxicity, and aquatic toxicity studies. We report here the toxicity results of a base set of hazard tests on a set of newly developed, well-characterized, ultrafine TiO(2) (uf-TiO(2)) particle-types. In vivo pulmonary toxicity studies in rats demonstrated low inflammatory potential and lung tissue toxicity. Acute dermal irritation studies in rabbits and local lymph node assay results in mice indicated that uf-TiO(2) was not a skin irritant or dermal sensitizer. Acute oral toxicity studies demonstrated very low toxicity and uf-TiO(2) produced short-term and reversible ocular conjunctival redness in rabbits. Genotoxicity tests demonstrated that uf-TiO(2) was negative in both the bacterial reverse mutation test and in an in vitro mammalian chromosome aberration test with Chinese hamster ovary cells. The results of aquatic toxicity screening studies demonstrated that uf-TiO(2) exhibited low concern for aquatic hazard in unaerated, 48h, static acute tests using the water flea, Daphnia magna; exhibited low concern for aquatic hazard in unaerated, 96h, static acute tests using the rainbow trout, Oncorhynchus mykiss; and exhibited medium concern in a 72h acute test using the green algae Pseudokirchneriella subcapitata. To summarize the findings, the results of most of the studies demonstrated low hazard potential in mammals or aquatic species following acute exposures to the ultrafine TiO(2) particle-types tested in this program.
authors.affiliation: DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714-0050, USA. david.b.warheit@usa.dupont.com
authors.forename: David B
authors.initials: DB
authors.lastname: Warheit
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hoke
authors.forename: Carol
authors.initials: C
authors.lastname: Finlay
authors.forename: E Maria
authors.initials: EM
authors.lastname: Donner
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Reed
authors.forename: Christie M
authors.initials: CM
authors.lastname: Sayes
mesh_terms: D000818:Animals; D016466:CHO Cells; D000460:Chlorophyta; D002869:Chromosome Aberrations / Q000139:chemically induced; D006224:Cricetinae; D003412:Cricetulus; D003621:Daphnia; D005128:Eye Diseases / Q000139:chemically induced / Q000473:pathology; D007509:Irritants; D023441:Local Lymph Node Assay; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009152:Mutagenicity Tests; D053758:Nanoparticles / Q000633:toxicity*; D017686:Oncorhynchus mykiss; D010316:Particle Size; D011791:Quartz / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D012308:Risk Management; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012871:Skin Diseases / Q000139:chemically induced / Q000473:pathology; D014025:Titanium / Q000633:toxicity*
chemical_list: D007509:Irritants; D011791:Quartz; C009495:titanium dioxide; D014025:Titanium