Abstract
Musk xylene (MX) is frequently used as a fragrance in commercial toiletries. Biotransformation of MX into 4-amino-MX (4-AMX) and 2-amino-MX (2-AMX) metabolites in rainbow trout haemoglobin (Hb) has been described. The dose-response relationship and toxicokinetics of the metabolites as adducts in the Hb were determined by gas chromatography (GC)-electron capture negative chemical ionization (NCI)-mass spectrometry (MS), and GC-electron ionization (EI)-MS/MS, using selected ion monitoring (SIM). The trout were subjected to a single exposure of 0.010, 0.030, 0.10, and/or 0.30 mg MX/g of fish. Hb samples were collected from exposed and control fish, and analysed subsequent to exposure at intervals of 24, 72, and 168 h. Alkaline hydrolysis released 4-AMX and 2-AMX metabolites from the Hb, and the solutes were extracted into n -hexane. The extracts were preconcentrated and analysed. The presence of the metabolites in the Hb extracts was confirmed based on agreement of similar mass spectral features from NCI/MS and EI-MS/MS spectra, and retention times of the metabolites with standards. The NCI/MS results were used for dose-response and toxicokinetics measurements. For dose-response, the concentrations of adducts of the metabolites increased with dosage, and a maximum adduct formation was observed at 0.10 mg g -1 , beyond which it decreased. The average concentrations of 4-AMX and 2-AMX at a dosage of 0.10 mg g -1 were 700 and 7.4 ng g -1 , respectively. For toxicokinetics, the concentration of the metabolites in the Hb reached a maximum in the 3 day sample after administration of MX. Further elimination of the metabolites exhibited kinetics with a half-life estimated to be 1-2 days, assuming first-order kinetics. Quantitations were made based on an internal standard and a calibration plot. In control samples, non-hydrolysed Hb, and reagent blank extracts, the metabolites were not detected. The limits of detection for 4-AMX and 2-AMX in the Hb were approximately 1.7 and 1.4 μg L -1 , respectively, based on a signal-to-noise ratio of 3 with NCI/MS.
| Original language | English |
|---|---|
| Pages (from-to) | 743-756 |
| Number of pages | 14 |
| Journal | International Journal of Environmental Analytical Chemistry |
| Volume | 86 |
| Issue number | 10 |
| DOIs | |
| State | Published - Aug 20 2006 |
Funding
This work was performed while the author (MAM) held a National Research Council Research Associateship Award at the National Exposure Research Laboratory, US Environmental Protection Agency (EPA), Las Vegas, Nevada. The authors would like to thank Dr L. I. Osemwengie for providing the 4-AMX and 2-AMX metabolite standards. The authors would like to thank Professor L. R. Curtis, Department of Environmental and Molecular Toxicology, 1007 Agricultural and Life Sciences, Oregon State University, Corvallis, OR 97331-7301, USA for providing all sorts of fish exposure facilities. The US Environmental Protection Agency, through its Office of Research and Development, collaborated in the research described in this article. It has been subjected to the EPA’s peer review and has been approved for publication. Mention of trade names or commercial products does not constitute an endorsement or recommendation for use. This article has been presented as poster in Society for Environmental Toxicology and Chemistry (SETAC) – South Central Regional Conference, 12–14 May 2005, Marble Falls, TX.
| Funders | Funder number |
|---|---|
| US Environmental Protection Agency (EPA), Las Vegas | EPA |
| National Research Council | |
| VA Office of Research and Development |
Keywords
- Biomarkers
- Dose-response
- Environmental exposure
- Hb adducts
- Nitro musks
- Toxicokinetics
ASJC Scopus subject areas
- Analytical Chemistry
- Environmental Chemistry
- Water Science and Technology
- Waste Management and Disposal
- Soil Science
- Pollution
- Public Health, Environmental and Occupational Health
- Health, Toxicology and Mutagenesis
