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Repeated dose 28-day oral toxicity study of moniliformin in rats
Martina Jonsson1, Janne Atosuo2, Marika Jestoi3
1Chemistry and Toxicology Research Unit, Finnish Food Safety Authority (Evira), Mustialankatu 3, Helsinki FI-00790, Finland.
Abstract:
Moniliformin is a Fusarium mycotoxin mainly produced by several species infecting grains in different climatic conditions. According to our previous studies, it is acutely toxic to rats, with an LD50 cut-off value of 25mg/kg b.w. To further assess the possible health risks of low dose exposure to moniliformin, a subacute oral toxicity study was conducted in Sprague-Dawley rats, adapting OECD guideline 407. Five dose groups and two satellite groups, each consisting of five male rats, were daily exposed to moniliformin by gavage. Two rats in the highest dose group, showed decreased activity followed by acute heart failure and death. The rats of the lower doses (<9mg/kg b.w.) showed no signs of toxicity. The daily intake of moniliformin strongly reduced the phagocytic activity of neutrophils in all dose groups. The decrease continued in the satellite group during the follow-up period, indicating a severe impact on the immune system and a LOAEL value of 3mg/kg b.w. for moniliformin. Moniliformin was rapidly excreted into urine, ranging between 20.2 and 31.5% daily and showed no signs of accumulation. The concentration of moniliformin in faeces was less than 2%, which suggests efficient absorption from the gastrointestinal tract.
Insights
Moniliformin, a Fusarium mycotoxin, severely impacts rat immune systems even at low doses, reducing neutrophil activity. This mycotoxin is rapidly excreted, showing no accumulation in the body.
Area of Science:
- Mycology
- Toxicology
- Immunology
Background:
- Moniliformin is a Fusarium mycotoxin found in grains.
- Previous studies indicated acute toxicity with an LD50 of 25mg/kg b.w. in rats.
Purpose of the Study:
- To assess the health risks of low-dose moniliformin exposure.
- To determine the subacute oral toxicity and immune effects in Sprague-Dawley rats.
Main Methods:
- Subacute oral toxicity study following OECD guideline 407.
- Daily gavage administration of moniliformin to male Sprague-Dawley rats in five dose groups and two satellite groups.
- Monitoring of clinical signs, mortality, neutrophil phagocytic activity, and mycotoxin excretion.
Main Results:
- Two rats in the highest dose group died from acute heart failure.
- No toxicity signs were observed in rats receiving <9mg/kg b.w. moniliformin.
- A significant reduction in neutrophil phagocytic activity was observed across all dose groups, with a continued decrease in the satellite group, establishing a LOAEL of 3mg/kg b.w.
- Moniliformin was rapidly excreted (20.2–31.5% daily) with minimal fecal concentration (<2%), indicating efficient absorption and no accumulation.
Conclusions:
- Low-dose moniliformin exposure poses a significant risk to the immune system, specifically impacting neutrophil function.
- The established LOAEL of 3mg/kg b.w. highlights the need for careful monitoring of moniliformin contamination in food sources.
- Rapid excretion and lack of accumulation suggest that the primary toxicological concern is the direct impact on immune function rather than chronic toxicity.
