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United States Department of Agriculture

Agricultural Research Service

Research Project: MINIMIZING THE ADVERSE HEALTH AND ECONOMIC IMPACTS OF MYCOTOXINS AND PLANT TOXINS IN FOODS Title: Hydrolyzed fumonisin B1 (HFB1) did not cause neural tube defects when evaluated using the LM/Bc mouse model

item Voss, Kenneth
item Burns, Tantiana - TOX PROG,UGEORGIA, ATHENS
item Snook, Maurice
item Riley, Ronald
item Gelineau-Van Waes, Janee - MED CEN/UNEBRASKA, OMAHA

Submitted to: United States-Japan Cooperative Program in Natural Resources
Publication Type: Abstract Only
Publication Acceptance Date: October 21, 2009
Publication Date: March 4, 2009
Citation: Voss, K.A., Burns, T., Snook, M.E., Riley, R.T., Gelineau-Van Waes, J. 2009. Hydrolyzed fumonisin B1 (HFB1) did not cause neural tube defects when evaluated using the LM/Bc mouse model. Proceedings of November, 2008,Scientific Presentations at the United States-Japan Cooperative Program in Natural Resources. November 2 - 7, 2008. New Orleans, LA.

Interpretive Summary: Abstract - no summary required

Technical Abstract: Fumonisins mycotoxins are found in corn and corn-based foods, usually at low concentrations. While it has been established that the most common fumonisin, fumonisin B1 (FB1), is toxic and carcinogenic to rodents, initial experiments produced no evidence that it is teratogenic. Results of more recent epidemiological surveys and laboratory experiments suggest however that consumption of tortillas made from corn likely containing relatively high levels of fumonisins contributed to an increase in the incidence of anencephaly, a type of neural tube defect (NTD), in southern Texas during 1990-1991 (Missmer et al. Environ. Health Persp. 114:237-41, 2006). FB1 has since been shown to cause NTD in the LM/Bc and CD1 mouse strains. In the more sensitive LM/Bc model, doses > 5 mg/kg (> 7 µmole/kg) BWt FB1 induced NTD when given by intraperitoneal injection to the dams at the critical time for neural tube closure. However, the teratogenic potential of hydrolyzed fumonisins found in tortillas and other alkaline cooked foods is unknown. Hydrolyzed FB1 (HFB1) was prepared by base hydrolysis of FB1 followed by solid phase extraction. Thereafter, groups of pregnant LM/Bc mice were given intraperitoneal injections of 2.5 to 20 mg/kg (corresponds to doses of 6 to 49 µmole/kg) BWt HFB1on embryonic days 7-8 and the litters examined on embryonic day 16. Negative and positive control groups were treated with vehicle or 10 mg/kg (14 µmole/kg) BWt FB1, respectively. NTD were not found in the groups treated with HFB1 and there were no significant differences between the negative control and the HFB1-exposed groups (n=8-9 litters/group) for the following variables (mean + S.D.): total implants (9.9 + 3.9 to 11.8 + 2.0/litter), viable fetuses (8.6 + 3.6 to 10.0 + 2.0/litter), early resorptions (0.9 + 1.0 to 1.7 + 2.0/litter), late fetal deaths (0.3 + 0.5 to 0.7 + 1.0/litter) and average weight of viable fetuses (0.47 + 0.09 g to 0.55 + 0.05 g). In contrast, FB1 caused NTD in all positive control litters (n=10). The number of NTD-positive fetuses/litter averaged 4.7 + 2.8, which corresponded to 66 + 24% of the total fetuses (viable plus dead). The number of implantations/litter (11.4 + 2.1) in the positive control group was similar to that of the other groups; however, early resorptions (4.6 + 3.0/litter) and fetal deaths (3.0 + 0.9/litter) were significantly (p < 0.05) increased and the number (3.9 + 2.1) and weight (0.33 + 0.7 g) of viable fetuses were significantly decreased. In summary, HFB1 did not cause NTD when evaluated using the LM/Bc mouse model at doses up to 7-fold greater (µmole/kg BWt basis) than the reported lowest observed adverse effect level for FB1.

Last Modified: 10/24/2014
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