Background: The aim of this study was to establish and validate a practical method to disperse nanoparticles in physiological solutions for biological in vitro and in vivo studies.

No abstract

The importance of nanotechnologies and engineered nanoparticles has grown rapidly. It is therefore crucial to acquire up-to-date knowledge of the possible harmful health effects of these materials. Since a multitude of different types of nanosized titanium dioxide (TiO(2)) particles are used in industry, we explored their inflammatory potential using mouse and cell models. BALB/c mice were exposed by inhalation for 2 h, 2 h on 4 consecutive days, or 2 h on 4 consecutive days for 4 weeks to several commercial TiO(2) nanoparticles, SiO(2) nanoparticles, and to nanosized TiO(2) generated in a gas-to-particle conversion process at 10 mg/m(3). In addition, effects of in vitro exposure of human macrophages and fibroblasts (MRC-9) to the different particles were assessed. SiO(2)-coated rutile TiO(2) nanoparticles (cnTiO(2)) was the only sample tested that elicited clear-cut pulmonary neutrophilia. Uncoated rutile and anatase as well as nanosized SiO(2) did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-alpha) and neutrophil-attracting chemokine CXCL1 in the lung tissue. TiO(2) particles accumulated almost exclusively in the alveolar macrophages. In vitro exposure of murine and human macrophages to cnTiO(2) elicited significant induction of TNF-alpha and neutrophil-attracting chemokines. Stimulation of human fibroblasts with cnTiO(2)-activated macrophage supernatant induced high expression of neutrophil-attracting chemokines, CXCL1 and CXCL8. Interestingly, the level of lung inflammation could not be explained by the surface area of the particles, their primary or agglomerate particle size, or radical formation capacity but is rather explained by the surface coating. Our findings emphasize that it is vitally important to take into account in the risk assessment that alterations of nanoparticles, e.g., by surface coating, may drastically change their toxicological potential.

In 1976-1992 245 new cases of asthma induced by diisocyanates were diagnosed, caused by hexamethylene diisocyanate (HDI) in 39%, diphenylmethane diisocyanate (MDI) in 39%, and toluene diisocyanate (TDI) in 17% of the cases. Our aim was to study the clinical outcome of diisocyanate-induced asthma. A questionnaire was sent to the 235 patients alive in 1995, and validated by reexamining clinically 91 of them. The study was carried out on average 10 () yr after the diagnosis. Of the patients 82% experienced symptoms of asthma, 34% used no medication, and 35% were on regular medication. The patients having displayed immunoglobulin E (IgE) antibodies to isocyanates used less medication (OR 0.273; CI 0.098, 0.758) and had fewer symptoms of asthma (OR 0.329; CI 0.124, 0.875) than the IgE-negative ones. They also had a significantly shorter duration of symptoms (p = 0.0025), latency period (p = 0.0249), and duration of exposure (p = 0.0008) than the IgE-negative patients. This did not, however, entirely explain the more favourable outcome of the IgE-positive patients. Patients with HDI-induced asthma used less medication (OR 0.412; CI 0.229, 0.739) than patients with MDI- and TDI-induced asthma. The results confirm the generally rather poor medical outcome of diisocyanate-induced asthma; the persistence of symptoms and unspecific bronchial reactivity were pronounced in TDI-induced asthma. A more favourable outcome was associated with IgE mediation and HDI inducement.