The risks of fumonisin B1 have been evaluated by The World Health Organization's International Programme on Chemical Safety and the Scientific Committee on Food of the European Commission. They determined a tolerable daily intake for FB1, FB2, FB3, alone or in combination of 2 μg/kg body weight. Until now, nothing about the kinetics and metabolism of fumonisin B1 in humans have been reported. On other animals much research has been done, but it might not be comparable to humans. In mice the elimination of FB1 is very rapid, but in humans it could be much slower considering their body weight. Epidemiological studies and clinical trials have pointed out folate deficiency as a major risk factor for neural tube defects. FB1 disrupts sphingolipid metabolism and therefore this could affect folate uptake and cause neural tube defects. Regions in China and South Africa with high corn consumption also have a high prevalence of neural tube defects.
Esophageal cancer It is thought that there is a relationship between the occurrence of
F. verticillioides and human esophageal cancer. A low socioeconomic status and a less varied diet, that mainly consists of corn and wheat, is associated with the appearance of esophageal cancer. On top of this it seems that people with a high corn intake are at higher risk to develop esophageal cancer than people with low corn intake. This is observed by people in regions in Italy, Iran, Kenia, Zimbabwe, United States and Brazil with high incidence of esophageal cancer. Another study on the relationship between sphingolipid levels and cancer incidence did not show any significant relationship between serum sphingolipids and risk of esophageal cancer. This is quite remarkable, because elevated levels of sphingolipids sphinganine and sphingosine are believed to be biomarkers for exposure of FB1. In pigs and rats there is a wide distribution of FB1 and small amounts have been found to accumulate only in liver and kidneys. In
vervet monkeys, some FB1 is partially hydrolyzed in the gut.
Porcine pulmonary edema Porcine pulmonary edema due to FB1 is intensively studied after the first report in 1981 of swine with pulmonary edema after exposure to corn contaminated with
F. verticillioides. Alteration in sphingolipid biosynthesis are reported, especially in lung, heart, kidney and liver tissue. Lethal pulmonary edema was developed within 4–7 days after exposure to feed with concentrations of FB1 >16 mg/kg body weight (>92 parts per million). Doses of 10 parts per million caused a milder form of pulmonary edema.
Toxicity in laboratory animals Effects of feeding rats with FB1 for up to 90 days were usually nephrotoxicity. Between different strains of rats, sensitivity to FB1 varied. In the kidneys the main effect was apoptosis. Also tubular atrophy and regeneration as well as decreased kidney weight was reported. Histopathologic effects on rat liver were reported after both short- and long-term exposure. The main cause was apoptosis. Mice do not seem to be very sensitive to nephrotoxic effects in comparison with rats. In mouse kidneys little histological changes were seen by high dose exposure. The liver was also the main target organ in mice. Pathology is similar as in rats, with apoptosis and hepatocellular hyperplasia. Fumonisin B1 is possibly embryotoxic if the dose is maternally toxic. A number of studies on genotoxicity indicated no mutagenetic effects. Although fumonisin could damage DNA directly by production of reactive oxygen species. Mouse embryos were exposed to FB1 and they showed inhibited sphingolipid synthesis and growth. It caused neural tube defects. Folic acid uptake was dramatically inhibited. Treatment after exposure with folic acid reduced neural tube defects by 50–65%. ==Tolerable daily intake==