title: Toxicity of nanoparticles embedded in paints compared with pristine nanoparticles in mice.
abstract: The unique physical and chemical properties of nanomaterials have led to their increased use in many industrial applications, including as a paint additive. For example, titanium dioxide (TiO2) engineered nanoparticles (ENPs) have well-established anti-UV, self-cleaning, and air purification effects. Silver (Ag) ENPs are renowned for their anti-microbial capabilities and silicon dioxide (SiO2) ENPs are used as fire retardants and anti-scratch coatings. In this study, the toxic effects and biodistribution of three pristine ENPs (TiO2, Ag, and SiO2), three aged paints containing ENPs (TiO2, Ag, and SiO2) along with control paints without ENPs were compared. BALB/c mice were oropharyngeally aspirated with ENPs or paint particles (20 μg/aspiration) once a week for 5 weeks and sacrificed either 2 or 28 days post final aspiration treatment. A bronchoalveolar lavage was performed and systemic blood toxicity was evaluated to ascertain cell counts, induction of inflammatory cytokines, and key blood parameters. In addition, the lung, liver, kidney, spleen, and heart were harvested and metal concentrations were determined. Exposure to pristine ENPs caused subtle effects in the lungs and negligible alterations in the blood. The most pronounced toxic effects were observed after Ag ENPs exposure; an increased neutrophil count and a twofold increase in pro-inflammatory cytokine secretion (keratinocyte chemoattractant (KC) and interleukin-1ß (IL-1ß)) were identified. The paint containing TiO2 ENPs did not modify macrophage and neutrophil counts, but mildly induced KC and IL-1ß. The paints containing Ag or SiO2 did not show significant toxicity. Biodistribution experiments showed distribution of Ag and Si outside the lung after aspiration to respectively pristine Ag or SiO2 ENPs. In conclusion, we demonstrated that even though direct exposure to ENPs induced some toxic effects, once they were embedded in a complex paint matrix little to no adverse toxicological effects were identified.
authors.affiliation: Center for Environment and Health, KU Leuven, Leuven, Belgium.
authors.forename: Stijn
authors.initials: S
authors.lastname: Smulders
authors.affiliation: Center for Environment and Health, KU Leuven, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Luyts
authors.affiliation: Centre for Surface Chemistry and Catalysis, KU Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Brabants
authors.affiliation: KU Leuven BIOMAT, Department of Oral Health Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Kirsten Van
authors.initials: KV
authors.lastname: Landuyt
authors.affiliation: Centre for Surface Chemistry and Catalysis, KU Leuven, Leuven, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Kirschhock
authors.affiliation: Division of Soil and Water Management, KU Leuven, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Smolders
authors.affiliation: CEA-Grenoble, Liten, 17 rue des Martyrs, France.
authors.forename: Luana
authors.initials: L
authors.lastname: Golanski
authors.affiliation: Center for Environment and Health, KU Leuven, Leuven, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Vanoirbeek
authors.affiliation: Center for Environment and Health, KU Leuven, Leuven, Belgium peter.hoet@med.kuleuven.be.
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D019570:Inhalation Exposure; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010150:Paint / Q000633:toxicity*; D012822:Silicon Dioxide / Q000493:pharmacokinetics / Q000633:toxicity*; D012834:Silver / Q000493:pharmacokinetics / Q000633:toxicity*; D013499:Surface Properties; D014018:Tissue Distribution; D014025:Titanium / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D016207:Cytokines; C009495:titanium dioxide; D012834:Silver; D012822:Silicon Dioxide; D014025:Titanium
keywords: in vivo; inhalation toxicology; mice; nanotoxicology; occupational health