Ochratoxin A (OTA), a mycotoxin produced by several fungi of Aspergillus and Penicillium
species, is a nephrotoxin and a renal carcinogen in rodents. This study was performed
to investigate the biotransformation and toxicokinetics of this important food contaminant.
Male (n=18) and female (n=18) F344 rats were administered a single dose of OTA (0.5
mg/kg b.w.) in corn oil by gavage. Animals (n=3) were sacrificed 24, 48, 72, 96, 672,
and 1,344 hours after OTA administration and concentrations of OTA and OTA-metabolites
in urine, feces, blood, liver, and kidney were determined by HPLC with fluorescence
detection and/or by LC-MS/MS. Recovery of unchanged OTA in urine amounted to 2.1%
of dose in males and 5.2% in females within 96 h. In feces, only 5.5% respectively
1.5% of dose were recovered. The major metabolite detected was OTalpha; low concentrations
of OTA-glucosides were also present in urine. The maximal blood levels of OTA were
observed between 24 and 48 h after administration and were appromixately 4.6 micromol/l
in males and 6.0 micromol/l in females. Elimination of OTA from blood followed first-order
kinetics with a half-life of approximately 230 h. In liver of both male and female
rats, OTA-concentrations were less than 12 pmol/g tissue, with a maximum at 24 h after
administration. In contrast, OTA accumulated in the kidneys, reaching a concentration
of 480 pmol/g tissue in males 24 h after OTA-administration. Generally, tissue concentrations
in males were higher than in females. OTalpha was not detected in liver and kidney
tissue of rats administered OTA, and the OTalpha concentrations in blood were low
(10-15 nmol/l). The high concentrations of OTA in kidneys of male rats may, in part,
explain the organ- and gender-specific toxicity of OTA.