Embryocidal, teratogenic and fetotoxic effects of citrinin in rats

Citrinin, a fungal metabolite produced by several species of Penicillium and Aspergillus, has been found to contaminate foods used by animals and man. Citrinin is nephrotoxic and has been implicated in disease outbreaks in animals and humans. In this study the teratogenicity, embryotoxicity, and fetotoxicity of citrinin was determined in Sprague-Dawley rats after subcutaneous administration of a single dose of 35 mg/kg on gestation day 3, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. Dams so treated lost weight for 2 days following administration. Subsequently, weight gain for treated animals was similar to that for controls. Relatively high maternal mortalities also were associated with this pretreatment regimen. Treatment with 35 mg/kg on certain days of gestation resulted in deaths of one half or more of the pregnant dams. No significant effects of citrinin were observed on the number of implants. Resorption of implants, however, was higher in treated animals than controls when dams were treated on days 6, 7, 8, 10, 11 or 12 of gestation. Fetuses from dams given citrinin were significantly smaller than those from controls by about 22% on average. No major gross or skeletal malformations were found in fetuses born to mothers which received citrinin. Major internal soft tissue malformations seen were enlarged kidneys, internal hydrocephalus and cleft palate.