Objective: Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO₂) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO₂in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome.Design: Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO₂nanoparticles. The proinflammatory effects of TiO₂particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO₂crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry.Results: Oral administration of TiO₂nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO₂-administered mice. In vitro, TiO₂particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1β and IL-18. TiO₂also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease.Conclusion: These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO₂nanoparticles.

This paper reviews the toxicokinetics of amphetamines. The designer drugs MDA (methylenedioxy-amphetamine, R,S-1-(3´,4´-methylenedioxyphenyl)2-propanamine), MDMA (R,S-methylenedioxymethamphetamine), and MDE (R,S-methylenedioxyethylamphetamine), as well as BDB (benzodioxolylbutanamine;R,S-1-(1´,3´-benzodioxol-5´-yl)-2-butanamine or R,S- 1-(3´,4´-methylenedioxyphenyl)-2-butanamine) and MBDB (R,S-N-methyl-benzodioxolylbutanamine), were taken into consideration, as were the following N-alkylated amphetamine derivatives: amphetaminil, benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, methamphetamine, prenylamine, and selegiline. English-language publications from 1995 to 2000 were reviewed. Papers describing identification of metabolites or cytochrome P450 isoenzyme-dependent metabolism and papers containing pharmacokinetic/toxicokinetic data were considered and summarized. The implications of toxicokinetics for toxicologic assessment or for interpretation in forensic cases are discussed.