Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans.
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 3H-labeled OTA (3.8 microCi). 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 (T1/2 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.
Studer-Rohr
I
I
Department of Environmental Toxicology, University of Konstanz, Germany.
Schlatter
J
J
Dietrich
D R
DR
D000465:Algorithms; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007553:Isotope Labeling; D009183:Mycotoxins / Q000097:blood* / Q000493:pharmacokinetics*; D009793:Ochratoxins / Q000097:blood* / Q000493:pharmacokinetics*
D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A