Cigarette smoke extract induced cytokine and chemokine gene expression changes in COPD macrophages.

Macrophages are key inflammatory cells in chronic obstructive pulmonary disease (COPD). The transcriptional regulation of inflammatory signalling pathways by cigarette smoke (CS) in COPD macrophages is not well understood. We have studied the effects of acute CS exposure on COPD macrophage cytokine, chemokine and signal transduction gene expression profiles.

Analysis of biomarkers in rats and dogs exposed to polymeric methylenediphenyl diisocyanate (pMDI) and its glutathione adduct.

Hemoglobin adducts (Hb-MDX) of monomeric methylenediphenyl diisocyanate (MDI) are often interpreted as indirect evidence of hydrolysis of the diisocyanate moiety to the respective amine (diphenylmethane-4,4'-diamine, 4,4'-MDA) which constitutes the rationale of using this biomarker as an internal dosimeter of exposure to putatively formed MDA. In contrast, more recently published data suggest that following inhalation the high concentration of glutathione (GSH) present in lungs favor an adduct formation with GSH and/or peptides/proteins rather than hydrolysis. The focus of this study was to test this alternate hypothesis, viz.

Absorption, distribution, metabolism and excretion of an inhalation dose of [14C] 4,4'-methylenediphenyl diisocyanate in the male rat.

The received dose, tissue distribution, metabolism, routes and rates of excretion of [(14)C]-4, 4(')-methylenediphenyl diisocyanate (MDI) were investigated in the male rat following a 6-h inhalation exposure to [(14)C]-MDI at a target concentration of 2 mg m(-3). The mean dose received was equivalent to 0.078 mg MDI per animal, of this between 25 and 32% of radiolabelled material was available systemically.

Titanium dioxide: inhalation toxicology and epidemiology.

Titanium dioxide (TiO(2)) is manufactured worldwide in large quantities for use in a wide range of applications and is normally considered to be toxicologically inert. Findings of tumours in the lungs of rats exposed chronically to high concentrations of TiO(2), but not in similarly exposed mice or hamsters, suggest that the tumorigenic response may be a rat-specific phenomenon but nonetheless raises concerns for potential human health effects. With the limited toxicological understanding of species differences in response to inhaled TiO(2) and a similarly limited amount of epidemiological information with respect to TiO(2) exposure in the workplace, a consortium of TiO(2) manufacturers in Europe (under the European Chemistry Industry Council; CEFIC) and in North America (under the American Chemistry Council; ACC) initiated a programme of research to investigate inter-species differences as a result of exposure to TiO(2) and to conduct detailed epidemiological surveys of the major manufacturing sites.

Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles.

A multispecies, subchronic, inhalation study comparing pulmonary responses to ultrafine titanium dioxide (uf-TiO(2)) was performed. Female rats, mice, and hamsters were exposed to aerosol concentrations of 0.5, 2.