Induction of ovarian toxicity in a subchronic oral toxicity study of citrinin in female BALB/c mice.

The present study was performed to elucidate toxicity profile of citrinin (CTN) after repeated oral doses for 90 days, especially on the kidneys and female reproductive organs using female BALB/c mice. We first performed a 70-day repeated oral dose toxicity study of CTN by setting the doses at 1.25 and 7.5 ppm in the drinking water (Experiment 1). As a result, CTN did not produce any toxicity in the kidneys, liver, and female genital organs/tracts, except for a slight increase of relative ovary weight. We, next, performed 90-day repeated oral dose toxicity study of CTN by increasing the dose levels at 15 and 30 ppm in the drinking water. The results suggested that CTN did not produce any toxicity in the kidneys, liver, and female genital organs/tracts, except for increase of both absolute and relative ovary weights accompanying increase of large follicles at ≥ 15 ppm. On the basis of these findings, the lowest-observable-adverse-effect level of CTN was 15 ppm (2.25 mg/kg body weight/day) in the drinking water for female BALB/c mice after 90-day oral treatment.