The carcinoGENOMICS project: Critical selection of model compounds for the development of omics-based in vitro carcinogenicity screening assays

Recent changes in the European legislation of chemical-related substances have forced the scientific community to speed up the search for alternative methods that could partly or fully replace animal experimentation. The Sixth Framework Program project carcinoGENOMICS was specifically raised to develop omics-based in vitro screens for testing...

Intragastric formation and modulation of N-nitrosodimethylamine in a dynamic in vitro gastrointestinal model under human physiological conditions

Human exposure to carcinogenic N-alkylnitrosamines can occur exogenously via food consumption or endogenously by formation of these compounds through nitrosation of amine precursors. Information on the intragastric formation of NDMA from complex mixtures of precursors and inhibitors in humans is not available. In this study the formation of N...

Health risks associated with inhaled nasal toxicants

Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and metabolism-based extrapolation of nasal data in...

Differential maintenance of cytochrome P450 enzymes in cultured precision-cut human liver slices

The maintenance of the major hepatic cytochrome P450 (CYP) enzymes has been studied in precision-cut human liver slices cultured for up to 72 h in supplemented RPMI 1640 medium. The relative apoprotein levels of 11 CYP enzymes were determined using a panel of antipeptide antibodes. In addition, 7-ethoxyresorufin O-deethylase, tolbutamide...

Lack of effect of coumarin on unscheduled DNA synthesis in the in vivo rat hepatocyte DNA repair assay

The ability of coumarin to induce UDS in male Sprague-Dawley CD rat hepatocytes in vivo was assessed using the unscheduled DNA synthesis (UDS) assay. From a preliminary toxicity study the oral maximum tolerated dose (MTD) of coumarin was determined to be 320mg/kg body weight. For the UDS studies, rats were treated with 0 (corn oil control), 32 ...

Effect of fumonisin B1 on rat hepatic P450 system

The effects of the mycotoxin fumonisin B1 (FB1) on the hepatic cytochrome P450 system were investigated in male rats dosed daily by oral gavage with 3 mg FB1 per kg body weight for 9 consecutive days. FB1 treatment resulted in a reduced weight gain. At the same time, CYP2E activity was increased, which is considered to mark the metabolic changes...

DNA adducts, mutant frequencies and mutation spectra in λlacZ transgenic mice treated with N-nitrosodimethylamine

Groups of λlacZ transgenic mice were treated i.p. with N-nitrosodimethylamine (NDMA) as single doses of 5 mg/kg or 10 mg/kg or as 10 daily doses of 1 mg/kg and changes in DNA N7- or O6-methylguanine or the repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT) were followed for up to 14 days in various tissues. Adduct induction in the liver...

Determination of volatile nitrosamines in cheese and cured meat products. Model study of a temperature- and pH-dependent artefact formation phenomenon in alkaline medium

Chemicals/CAS: dimethylnitrosamine, 62-75-9; Nitrosamines

Gezondheidsaspecten van het werken met metaalbewerkingsvloeistoffen: een praktijkoriëntatie

Onderzoek werd verricht in 11 bedrijven waar regelmatig met metaalbewerkingsvloeistoffen wordt gewerkt. Bij de aanschaf van waterhoudende vloeistoffen wordt door de meeste bedrijven weinig rekening gehouden met gezondheidseffecten. Er werden monsters genomen die geanalyseerd werden op aanwezigheid van o.a. N- Nitrosodiethanolamine (NDELA). In op...

Report of a workshop on bacterial in vitro mutagenicity test systems

Bacterial systems for the screening of chemical substances for mutagenic potential are receiving widespread attention. Now that many laboratories have introduced these test systems and a large number of substances has been tested, discrepancies in the results have become apparent. To discuss this problem, a workshop was organized at Neuherberg ...