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Title: Fetotoxicity and neural tube defects on CD1 mice exposed to the mycotoxin fumonisin b1

Author
item Voss, Kenneth
item Riley, Ronald
item GELINEAU-VAN WAES, J. - U NE MED CEN, OMAHA

Submitted to: International Symposium of Mycotoxicology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 12/4/2006
Publication Date: 12/13/2006
Citation: Voss, K.A., Riley, R.T., Gelineau-Van Waes, J.B. 2006. Fetotoxicity and neural tube defects on CD1 mice exposed to the mycotoxin fumonisin b1. International Symposium of Mycotoxicology Meeting. December 13-14,2006. Bangkok, Thailand.

Interpretive Summary: Abstract - no summary needed.

Technical Abstract: The fumonisin mycotoxins are produced by Fusarium verticillioides and F. proliferatum. They occur commonly in maize and maize-based foods. The human health effects of fumonisins are unclear. There is however epidemiological and experimental evidence suggesting that these mycotoxins interfere with folate utilization and increase the risk for neural tube defects (NTDs) in human populations consuming large amounts of foods prepared from contaminated maize. FB1 was not teratogenic when given by gavage to pregnant CD1 mice (Reddy et al., Mycopathologia 134, 161-166, 1996), rats or rabbits during organogenesis. The litters of CD1 females fed diets containing fumonisins (150 ppm FB1, provided by F. verticillioides culture material, beginning > 5 weeks before mating) exhibited fetotoxicity but no NTDs. In contrast, NTDs were induced (100% of the litters were NTD positive at doses > 15 mg/kg body weight) when FB1 was given to females of the inbred LM/Bc mouse strain by intraperitoneal injection at the critical time during gestation for neural tube closure. To determine if CD1 mice are susceptible to NTD induction by fumonisins, FB1 was given to females by intraperitoneal injection on gestation days 7 and 8 at doses of 0, 15, 30 and 45 mg/kg body weight (Study 1) or 0, 10, 23, 45 or 100 mg/'kg body weight (Study 2). FB1 was fetotoxic at doses > 45 mg/kg body weight FB1 as indicated by a reduction in the average number of live fetuses per litter, increased number of resorptions per female, and decreased average litter weights. A dose-related increase in the number of NTD positive litters was observed in both studies: four of 10 litters in Study 1 and four of 11 litters in Study 2 were NTD positive at 45 mg/kg body weight FB1 and six of 11 litters from the high-dose group of Study 2 (100 mg/kg body weight FB1) were affected. A no observed effect level was not established as NTD affected fetuses were found in one of 9 and one of 10 low-dose litters from Studies 1 and 2, respectively. In conclusion, NTD induction by FB1 is not unique to LM/Bc mice. CD1 litters are also susceptible when FB1 is given to the females by intraperitoneal injection, although dose-response data suggest the CD1 strain is less sensitive than the LM/Bc strain. Comparative investigations using these and other mouse strains will be useful for determining the mechanism of NTD formation in fumonisin-treated mice and the relevance of these animal models to humans.