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Oral Deoxynivalenol Toxicity in Sprague Dawley Rat dams and their offspring

Madelyn C. Huang, Johnathan R. Furr, Veronica G. Robinson, Laura Betz, Keith Shockley, Helen Cunny ,Kristine Witt, Suramya Waidyanatha, Dori Germolec

DOI: https://doi.org/10.22427/NTP-DATA-002-03342-0004-0000-8

Publication

Abstract

Deoxynivalenol (DON) is a fungal mycotoxin found in many grain-based foods and animal feed globally and there is widespread human exposure. While acute exposure to high levels of DON is associated with gastrointestinal effects and emesis, the effects of low dose, long-term exposure to DON are understudied. Exposure to DON may also have reproductive and developmental effects on animals, such as malformations and/or lower body weight. However, these effects often occur at doses that also result in maternal toxicity. Thus, it is currently unclear if developmental effects are due to DON itself or due to maternal toxicity. This study was designed to identify doses of DON that could be used to evaluate long-term and reproductive and developmental toxicity following perinatal exposure. Time-mated Harlan Sprague Dawley (Hsd:Sprague Dawley® SD®) rats were administered 0, 0.03, 0.1, 0.3, 1, or 3 mg/kg/day of DON once daily via gavage starting on gestation day 6 through postnatal day (PND) 27. Dosing for F1 animals was initiated via gavage on PND 12 through PND 27, at the same dose as their respective dam. Animals were euthanized on PND 28. DON had no effect on maternal body weight or feed consumption at any dose. Findings were limited to the 3 mg/kg/day group: F0 females had smaller live litter size than controls and F1 pups had lower body weight (4-13%) compared to controls. By PND 28, F1 body weight, after adjustments for litter effects, was 10-13% lower than controls. Blood sampled for micronuclei determination on PND 28 showed no change in micronucleated immature erythrocytes in both F0 and F1 animals. In summary, doses of DON up to 3 mg/kg/day did not affect maternal survival or body weight and doses of 3 mg/kg/day showed slight toxicity in offspring manifested as decreased body weight. These doses can be used in future studies to evaluate the effects of DON exposure, such as carcinogenicity and reproductive and developmental toxicity.

Modified One Generation Dose Range Finding Study

Study Tables

Individual Animal Data