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Title: DEVELOPMENTAL TOXICITY OF DIETS CONTAINING FUMONISIN B1 TO LM/BC AND CD1 MICE: A COMPARATIVE STUDY

Author
item Voss, Kenneth
item GELINEAU VAN-WAES, J - MED.CEN/U.NEBRASKA,OMAHA
item Riley, Ronald
item BURNS, T - TOX.PROG/U.GEORGIA
item Bacon, Charles

Submitted to: Toxicological Sciences
Publication Type: Abstract Only
Publication Acceptance Date: 1/30/2005
Publication Date: 3/15/2005
Citation: Voss, K.A., Gelineau Van-Waes, J.B., Riley, R.T., Burns, T.D., Bacon, C.W. 2005. Developmental toxicity of diets containing fumonisin B1 to LM/BC and CD1 mice: a comparative study. Toxicological Sciences. 84:(S1):1396.

Interpretive Summary: Abstract - no summary

Technical Abstract: Fumonisin mycotoxins are found in corn and corn-based food. Their health effects in humans are unknown, however, it has been suggested that they might be a risk factor for neural tube defects (NTDs) in populations consuming contaminated corn as a diet 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 caused NTDs in the fetuses. 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 fungal culture material) beginning 5 weeks before mating. Pregnant females and their litters (mating produced >5/group) were examined for gross malformations, especially NTDs, by necropsy after GD 16. The high-dose diet was maternally toxic to both strains as established by microscopic examination of the maternal livers. Within each strain, no significant effects on mating, fertility, maternal weight, and litter weight or size were noted. Neither fetotoxicity nor NTDs were found in control or low-dose litters. One of five (20%) LM/Bc high-dose litters were positive for NTDs (1 of 10 fetuses were affected). No NTDs were found in CD1 litters (n=7-9) but, in contrast to the LM/Bc strain, fetotoxicity was found in two high-dose litters; 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) maternal toxicity is a prerequisite for NTD development; (c) strain-dependent differences in sensitivity to NTDs exist; and (d) studies are needed to define the NTD dose-response and the physiological factors underlying NTD development in FB1-fed mice.