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Title: MATERNAL AND FETAL TOXICITY OF FUMONISIN-PRODUCING FUSARIUM VERTICILLIOIDES CULTURE MATERIAL IN LM/BC AND CD1 MICE.

Author
item Voss, Kenneth
item GELINEAU-VAN WAES, J - MED CEN/UNEBRASKA/OMAHA
item Riley, Ronald
item BURNS, T - TOX PROG/UGEORGIA/ATHENS
item Bacon, Charles

Submitted to: US-Japan Coop Pgm on Dev and Util of Natural Products Abstracts Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 10/1/2004
Publication Date: 11/8/2004
Citation: Voss, K.A., Gelineau-Van Waes, J.B., Riley, R.T., Burns, T.D., Bacon, C.W. 2004. Maternal and fetal toxicity of fumonisin-producing fusarium verticillioides culture material in lm/bc and cd1 mice. United States-Japan Cooperative Program on Development and Utililization of Natural Resources. Abstracts Proceedings. Nov 8-12,2004. Atlanta, GA.

Interpretive Summary: Abstract of presentation - no interpretive summary required.

Technical Abstract: Fumonisins are mycotoxins found in corn and corn-based food. Their health effects in humans are unknown; however, they might be a risk factor for neural tube defects (NTDs) in populations consuming foods made from contaminated corn as a dietary staple. Fumonisin B1 (FB1) was not teratogenic when given orally to pregnant CD1 mice during gestation days (GD) 7-15 whereas intraperitoneal injection of > 5 mg/kg BW FB1 to pregnant LM/Bc mice on GD 7.5-8.5 did cause NTDs in the fetuses. The reasons underlying the different results are unknown but could be related to dose level, route of administration, or mouse strain. To compare NTD susceptibility in these two strains, female LM/Bc (n=8/group) and CD1 mice (n=10/group) were fed diets containing 0 (control), 50 or 150 ppm FB1 (provided by F. verticillioides culture material) beginning 5 weeks before mating. The females and their litters (mating produced >5 litters/group) were examined for gross malformations, especially NTDs in the fetuses, by necropsy and caesarian section after GD 16. The high-dose diet was maternally toxic to both strains as established by microscopic examination of the maternal livers. The hepatic lesions were consistent with the effects of fumonisins. Within each strain, no significant effects on mating, fertility, maternal weight, and litter size were noted. Neither fetotoxicity nor NTDs were found in control and low-dose litters of either strain. One of five (20%) LM/Bc high-dose litters was positive for NTDs (1 of 10 fetuses affected) whereas no NTDs were found in the high dose CD1 litters. In contrast to the LM/Bc strain, the high dose diet caused fetotoxicity in two of nine high-dose CD1 litters examined by caesarian section; the incidence of dead fetuses therein ranged from 40 to 64%. These results suggest that (a) the dietary NOEL for NTDs in LM/Bc mice is > 50 ppm FB1; (b) NTDs develop in LM/Bc mice at maternally toxic doses; (c) strain-dependent differences in sensitivity to fetotoxicity and NTDs exist; and (d) additional studies are needed to define the NTD dose-response and the physiological factors underlying NTD development in FB1-fed mice.