Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Fabian, E; Bordag, N; Herold, M; Kamp, H; Krennrich, G; Looser, R; Ma-Hock, L; Mellert, W; Montoya, G; Peter, E; Prokudin, A; Spitzer, M; Strauss, V; Walk, T; Zbranek, R; van Ravenzwaay, B.
Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.
Toxicol Lett. 2016; 255: 11-23.
Doi: 10.1016/j.toxlet.2016.05.003
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Bordag Natalie
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- Abstract:
- The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Administration, Inhalation -
- Administration, Oral -
- Aniline Compounds - administration & dosage
- Aniline Compounds - pharmacokinetics
- Aniline Compounds - toxicity
- Animals -
- Benzene Derivatives - administration & dosage
- Benzene Derivatives - pharmacokinetics
- Benzene Derivatives - toxicity
- Chloroform - administration & dosage
- Chloroform - pharmacokinetics
- Chloroform - toxicity
- Databases, Factual -
- Dimethylformamide - administration & dosage
- Dimethylformamide - pharmacokinetics
- Dimethylformamide - toxicity
- Dose-Response Relationship, Drug -
- Drug Administration Schedule -
- Ethylene Glycols - administration & dosage
- Ethylene Glycols - pharmacokinetics
- Ethylene Glycols - toxicity
- Female -
- Furans - administration & dosage
- Furans - pharmacokinetics
- Furans - toxicity
- Inhalation Exposure -
- Male -
- Metabolome -
- Metabolomics -
- Principal Component Analysis -
- Rats, Wistar -
- Risk Assessment -
- Toxicity Tests -
- Find related publications in this database (Keywords)
- Rat
- Plasma metabolome
- Oral versus inhalative exposure