Kinetic parameters and intraindividual fluctuations of ochratoxin A plasmalevels 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 plas ma (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 39 5 ng H-3-labeled OTA (3.8 mu Ci). A two-compartment open model consisting o f a central compartment was found to best describe the in vivo data. This t wo-compartment model consisted of a fast elimination and distribution phase (T-1/2 about 20 h) followed by a slow elimination phase (renal clearance a bout 0.11 ml/min.) and a calculated plasma half-life of 35.55 days. This ha lf-life was approximately eight times longer than that determined previousl y in rats, In addition, the intraindividual fluctuation of OTA plasma level s was investigated in eight individuals over a period of 2 months, The conc entrations determined ranged between 0.2 and 0.9 ng OTA/ml plasma. The plas ma levels in some individuals remained nearly constant over time, while oth ers 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 intraindiv idual fluctuation in OTA plasma levels, which may represent differences in OTA exposure and/or metabolism, as well as the large difference in plasma h alf-life in humans compared to rats must be taken into consideration when t he results of rat cancer study data are extrapolated to humans for risk ass essment purposes.