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Citrinin is a product of fungal metabolism capable of producing nephrotoxicity. Distribution, excretion and metabolism of [14C]citrinin was studied in pregnant female rats after subcutaneous administration of 35 mg/kg on the 12th day of gestation. Elimination of [14C]citrinin-derived radioactivity from plasma was biphasic. The half-lives for the rapid (alpha) and slower (beta) phases of elimination were 1.95 h and 39.7 h, respectively. Approximately 74% of the radioactivity appeared in the urine in the first 24 h, with only 1.7% and 1.4% in the urine at 48 h and 72 h, respectively. Fecal elimination accounted for 9.5%, 4.1% and 7.3% of the total radioactivity at each of these times. At least one metabolite of citrinin was demonstrable with high performance liquid chromatography (HPLC) of plasma extracts. Retention times for the parent compound and metabolite were 270 s and 175 s, respectively. The metabolite was more polar than the parent compound. At least 2 metabolites of citrinin were found in urine of the same rats. Retention times for two metabolites were 140 s and 180 s, with both metabolites more polar than the parent compound. Chromatograms of bile samples suggested at least one metabolite was present with a retention time of 140 s. Chromatograms of uterus extracts indicated the presence of one metabolite with a retention time of 180 s. Chromatograms of fetus extracts indicated that no metabolites of citrinin were present.

The mycotoxin citrinin is a potent inducer of chromosomal aberrations in the clastogenicity assay on V79-E cells when metabolized by rat and human liver microsomes. Rat and human liver microsomes, standardized on protein content, activate citrinin at equal levels. 5 X 10(-4) M citrinin induces complex translocations in a high frequency as well as defects of chromosomal coiling. Higher concentrations are cytotoxic, lower ones are almost inactive. After metabolization of mycotoxin by rat-kidney microsomes or an S9 mix fraction containing rat liver and kidney microsomes, toxic effects predominate and chromosomal aberrations are diminished. Clastogenic citrinin concentrations do not induce an increase of SCE frequency. Although the mode of action of this mycotoxin on chromosomal structure remains obscure, possible explanations are discussed.