A reproductive and developmental screening study of the fungal toxin ochratoxin A in Fischer rats
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The presence of the mycotoxin ochratoxin A (OTA) in cereal grains is due to the growth of toxigenic Penicillium mold on stored crops. Human exposure to OTA is higher in infants, toddlers, and children than in adolescents and adults, based on exposure assessments of ng OTA consumed/kg body weight/day. Ochratoxin A is nephrotoxic and teratogenic in animals, but its effects on juveniles exposed during the reproduction and development period have not been studied. To address this, Fischer rats were exposed to 0, 0.16, 0.4, 1.0, or 2.5 mg OTA/kg diet throughout breeding, gestation, and lactation and its adverse effects were assessed in adult rats and their offspring on postnatal day (PND) 21. There were no effects on implantation but post-implantation fetotoxicity was observed in the 2.5 mg/kg dose group, corresponding to a calculated dose of 167.0 μg/kg bw/day in dams. Adverse effects on body and kidney weights and on clinical parameters indicative of renal toxicity were significant in adult rats exposed to 1.0 mg OTA/kg diet (55.2 and 73.3 μg/kg bw/day in adult males and females, respectively) and in PND21 rats at the 0.4 mg/kg dose (33.9 μg/kg bw/day in dams), suggesting that weanling rats were more sensitive to OTA than adults. Overall, nephrotoxicity was the primary effect of OTA in weanling rats exposed throughout gestation and lactation at sub-fetotoxic concentrations in diet.
KeywordsFetotoxic Kidney Ochratoxin A Rat Reproduction
The authors would like to acknowledge the valuable assistance and input from the following: Jennifer Eastwood, Mark Feeley, Zoe Gillespie, Marnie Taylor, Christine Bourque, Gerard Cooke, Santokh Gill, and the staff of Health Canada’s animal facility, as well as Dan Cyr and Mary Gregory (INRS-Institut Armand Frappier, Université du Québec, Laval, Quebec, Canada).
Source of funding
This research was funded by the Food Directorate, Health Canada.
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest to declare and have agreed to allow the journal to review the data in this manuscript.
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