Fetotoxicity and neural tube defects in CD1 mice exposed to the mycotoxin fumonisin B1

Abstract

Fumonisins are produced by Fusarium verticillioides and occur in maize and maize-based foods. Their effects on human health are unclear, however, epidemiological and experimental evidence suggest that they increase the risk of neural tube defects (NTDs) in populations routinely consuming foods prepared from contaminated maize. When given orally to CD1 mice and other laboratory species, fumonisin B1 (FB1) was fetotoxic, but not teratogenic. However, intraperitoneal (ip) injection of FB1 to inbred LM/Bc mice at the critical time for neural tube closure elicited NTDs in a dose-dependent manner. To determine if CD1 mice are susceptible to induction of NTDs by fumonisins, 10 to 100 mg/kg body weight (BWt) FB1 was given ip to females on gestation days 7 and 8. FB1 was fetotoxic at maternal doses≥45 mg/kg BW. The number of litters with one or more NTD-affected fetuses increased in a dose-dependent manner, reaching a maximum of 55 % (six of 11 litters) at 100 mg/kg BW. A no observed adverse affect level was not established as 10 % of litters at the lowest dose, 10 mg/kg BW FB1, were NTD positive. These results demonstrated that NTD induction by FB1 in mice is not unique to the LM/Bc strain. They further showed that CD1 mice are less sensitive to NTD induction by FB 1 than LMBc mice. Comparative investigations using these and other strains will be useful for determining the mechanisms of NTD induction in fumonisin-treated mice and the relevance of these animal models to humans.