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United States Department of Agriculture

Agricultural Research Service

Title: Fumonisins and Neural Tube Defects: Reproductive Toxicity Studies in the Lm/bc and Cd1 Mouse Strains

Authors
item Voss, Kenneth
item Riley, Ronald
item Gelineau-Van Waes, J - GENETICS, U.NE, OMAHA, NE

Submitted to: Food Safety International Conference
Publication Type: Abstract Only
Publication Acceptance Date: February 15, 2006
Publication Date: February 15, 2006
Citation: Voss, K.A., Riley, R.T., Gelineau-Van Waes, J.B. 2006. FUMONISINS AND NEURAL TUBE DEFECTS: REPRODUCTIVE TOXICITY STUDIES IN THE LM/BC AND CD1 MOUSE STRAINS. Food Safety International Conference. February 15-16,2006. Sydney Australia.

Interpretive Summary: Abstract - no interpretive

Technical Abstract: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides that is found in maize and maize-based foods. Reproductive studies in CD1 mice, rats and rabbits initially found no evidence that fumonisins are teratogenic. However, more recent epidemiological observations and laboratory findings suggest that they might increase the risk of neural tube defects (NTDs) in populations consuming large amounts of fumonisin-contaminated maize. When >15 mg/kg body weight fumonisin B1 (FB1) was given to pregnant LM/Bc mice by intrapteritoneal injection (ip), all litters were positive for NFDs. To determine if NTD induction is unique to the inbred LM/Bc mouse strain, NTD induction in LM/Bc and providing <150 ppm FB1 (Study 1, both strains) or <300 ppm FB1 (Study 2, LM/Bc strain only) was fed to female mice before and during gestation, and (b) in experiments (Studies 3 and 4) in which FB1 was given ip to CD1 dams on gestation days 7 and 8, the critical time for NTD development. In Study 1, one of five LM/Bc litters from dams fed the 150 ppm FB1 diet was positive for NTDs whereas no NTDs were found in the CD1 litters. No NTDs were found however in the LM/Bc litters from Study 2. Forty percent of the litters from dams given FB1 ip at the highest dose tested during Study 3, 45 mg/kg body weight, were positive for NTDs and one of ten low-dose (15 mg/kg body weight) litters was also affected. These results were corroborated by those by Study 4 in which FB1 caused a dose-related increase in the incidence of NTD-positive litters. The percent of litters affected ranged from 8% at the low dose of 10 mg/kg FB1 to 55% at the high dose of 100 mg/kg body weight. Thus, the results of the feeding studies were inconclusive and additional investigations are needed to determine whether or not exposure to fumonisin-contaminated diets induce NTDs in mice. In contrast, ip exposure to FB1 does induce NTDs in both the LM/Bc and CD1 mouse strains, although the latter strain appears to be considerably less sensitive. Comparative investigations sing these strains will be useful for elucidating the mechanisms underlying FB1-induced NTDs in mice and determining the suitability of the LM/Bc and other mouse models for studying the relationships between fumonisins and NTDs in humans.

Last Modified: 8/27/2014