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Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans

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2000

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Studer-Rohr, Irène
Schlatter, Josef

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Archives of Toxicology. 2000, 74(9), pp. 499-510. ISSN 0340-5761. eISSN 1432-0738

Zusammenfassung

The mycotoxin ochratoxin A (OTA) is a rodent carcinogen produced by species of the ubiquitous fungal genera Aspergillus and Penicillium. OTA is found in a variety of food items and as a consequence is also found in human plasma (average concentrations found in this study: 0.1-1 ng OTA/ml plasma). To improve the scientific basis for cancer risk assessment the toxicokinetic profile of OTA was studied in one human volunteer following ingestion of 395 ng [3]H-labeled OTA (3.8 μCi). A two-compartment open model consisting of a central compartment was found to best describe the in vivo data. This two-compartment model consisted of a fast elimination and distribution phase (T[1/2] about 20 h) followed by a slow elimination phase (renal clearance about 0.11 ml/min.) and a calculated plasma half-life of 35.55 days. This half-life was approximately eight times longer than that determined previously in rats. In addition, the intraindividual fluctuation of OTA plasma levels was investigated in eight individuals over a period of 2 months. The concentrations determined ranged between 0.2 and 0.9 ng OTA/ml plasma. The plasma levels in some individuals remained nearly constant over time, while others varied considerably (e.g. increase of 0.4 ng/ml within 3 days, decrease of 0.3 ng/ml within 5 days) during the observation period. This intraindividual fluctuation in OTA plasma levels, which may represent differences in OTA exposure and/or metabolism, as well as the large difference in plasma half-life in humans compared to rats must be taken into consideration when the results of rat cancer study data are extrapolated to humans for risk assessment purposes.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Ochratoxin A, Kinetics, Humans, Plasma levels, Cancer risk extrapolation

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ISO 690STUDER-ROHR, Irène, Josef SCHLATTER, Daniel R. DIETRICH, 2000. Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans. In: Archives of Toxicology. 2000, 74(9), pp. 499-510. ISSN 0340-5761. eISSN 1432-0738
BibTex
@article{StuderRohr2000Kinet-6966,
  year={2000},
  title={Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans},
  number={9},
  volume={74},
  issn={0340-5761},
  journal={Archives of Toxicology},
  pages={499--510},
  author={Studer-Rohr, Irène and Schlatter, Josef and Dietrich, Daniel R.}
}
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