ARS | Publication request: Fetotoxicity and neural tube defects in CD1 mice exposed to the mycotoxin Fumonisin B1

Submitted to: Mycotoxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 1, 2007
Publication Date: December 31, 2007
Citation: Voss, K.A., Riley, R.T., Gelineau Van-Waes, J. 2007. Fetotoxicity and neural tube defects in CD1 mice exposed to the mycotoxin Fumonisin B1. International Symposium of Mycotoxicology Meeting. Mycotoxins 57S:67-72.

Interpretive Summary: Fumonisins are toxins produced by Fusarium molds found on corn and found in corn-based foods. Some evidence suggests that fumonisins increase the risk of a type of serious birth defect, called neural tube defect, in populations heavily dependent on corn-based foods contaminated with fumonisins as dietary staple. Animal experiments have given mixed results. In one study, fumonisin B1 (FB1) did not cause neural tube defects when given orally to pregnant CD1 mice, a mouse strain routinely used in research, during gestation days 6-15. In contrast, FB1 did cause neural tube defects in another type of mouse, the LM/Bc strain, when given by intraperitoneal injection on gestation days 7 and 8. To determine if the differences in these results was due to the type of mouse used or to the route and timing of FB1 treatment, we gave FB1 to pregnant CD1 mice by intraperitoneal injection on gestation days 6-15. When given in this manner, FB1 caused neural tube defects in the CD1 mice. Dose-response indicated, however, that the CD1 mice are less sensitive to this effect than the LM/Bc strain. Comparative studies using these mouse strains will be useful for determining the mechanisms underlying fumonisin-induced neural tube defects in mice and provide information to further assess the potential risk of neural tube defects in humans exposed to these mycotoxins.

Technical Abstract: Fumonisins are mycotoxins that are produced by Fusarium verticillioides and that occur in corn and corn-based foods. Their effects on human health are unclear, however, epidemiological and experimental evidence suggests that they increase the risk of neural tube defects (NTDs) in populations routinely consuming large amounts of food prepared from contaminated corn. 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 NTD formation 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 BWt. The number of litters with one or more NTD-affected fetuses increased in a dose-dependent manner, reaching a maximum of 55 percent (six of 11 litters) at 100 mg/kg BWt. A no observed adverse affect level was not established, as 10% of the litters at the lowest dose, 10 mg/kg BWt FB1, were NTD positive. These results demonstrate that NTD induction by FB1 in mice is not unique to the LM/Bc strain. They further show that CD1 mice are inherently less sensitive to NTD induction by FB1 than LM/Bc 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.