Intermediate-duration toxicity study of patulin in rats

The toxicity of patulin was studied in two generations of Sprague-Dawley rats over a period of approximately 10 months. Patulin in 1 mM citrate buffer was administered by gavage to FO generation rats at a dose level of 0, 1.5, 7.5, or 15.0 mg/kg a body weight five times a week for 10-14 wk; females were treated seven times a week during pregnancy. High mortality and insufficient progeny in the groups given 7.5 and 15.0 mg/kg made it impossible to continue those two regimens into the second generation. The study was continued for 20-23 wk with F1A generation animals given 1.5 mg/kg and controls. The only lesion found at necropsy that could be attributed to patulin administration was gaseous distention of the gastrointestinal tract, which was probably the result of the antibiotic effect of this mycotoxin on the normal intestinal flora. A decreased weight gain in male rats of the FO generation was dose-related. An impairment in growth rates of F1A and F2A progeny of both sexes was statistically significant at the 1.5 mg/kg dose level. Fetuses taken from patulin-treated females on day 20 of pregnancy were noticeably smaller than controls fetuses and the difference was significant for F2A males. No other teratological abnormalities related to patulin dosing at the 1.5 mg/kg level were observed consistently in either F1A or F2A fetuses. Patulin did not appear to produce dominant lethal effects at dose levels up to 15.0 mg/kg when given by gavage to the males five times a week for 10 or 11 wk.