Nivalenol (NIV) is a mycotoxin of the trichothecene group. In nature it is mainly found in fungi of the Fusarium species. The Fusarium species belongs to the most prevalent mycotoxin producing fungi in the temperate regions of the northern hemisphere, therefore making them a considerable risk for the food crop production industry. The fungi are abundant in various agricultural products (cereal crops) and their further processed products (malt, beer and bread). "The Fusarium species invade and grow on crops, and may produce nivalenol under moist and cool conditions". In pigs, the symptoms observed after nivalenol exposure are "feed refusal, vomiting, gastroenteric and dermal irritation or necrosis and immunological dysfunction", as well as haematotoxicity, resulting in a low leukocyte count.
History In the period of 1946 to 1963, several cases of intoxication due to the ingestion of Fusarium infected grains (scrabby grain disease) were reported in Japan, Korea and India. There have been no reports of lethal cases and only mild symptoms like nausea, vomiting, diarrhea and abdominal pain. In these incidents F. graminaerum could be isolated, which hints at a nivalenol or deoxynivalenol contamination. In the same period two outbreaks involving over 100 cases were reported in India and China. These outbreaks were also non-lethal. A well documented and acute outbreak in India in 1987 affected around 50,000 thousand people. Several Fusarium toxins under which nivalenol (0.03–0.1 mg/kg in 2 of 24 samples), deoxynivalenol (0.34–8.4 mg/kg in 11 of 24 samples) and acetyldeoxynivalenol (0.6–2.4 mg/kg in 4 of 24 samples) were found in rain-damaged wheat used for bread production. There were again no lethal cases and reported symptoms were abdominal pain, diarrhea, bloody stool and vomiting. These cases show that the main emerging danger of nivalenol comes from Fusarium infected cereals and is mainly via the route of digestion of uncontrolled wheat or other grains that are further processed or does enter the food chain via another route.
Weaponization and other instances of nivalenol poisoning Nivalenol as well as deoxynivalenol and T-2 toxin have been used as biological warfare agents in Laos and Cambodia as well as in Afghanistan. The Soviet Union has been alleged to have provided the mycotoxins and to have used them themselves in Afghanistan. All three compounds could be identified in the vegetation at affected sites, whereas T-2 toxin could also be found in urine and blood samples of victims. The best documented use of trichothecenes in warfare is the yellow rain controversy, a number of attacks in Southeastern Asia, Laos and Afghanistan which used a "yellow rain" as described by witnesses. The toxins were delivered as a cloud of yellow dust or droplets. An article by L. R. Ember published in 1984 in Chemical Engineering News describes the use of trichothecene mycotoxins as biological weapons in Southeast Asia in a very detailed manner, covering reports of survivors, eyewitnesses, prisoners of war and Soviet informants along with information on the presence of Soviet technicians and laboratories. This led to the conclusion that these toxins have been used in Southeast Asia and Afghanistan. The Russian government however refuses to give a statement on these pieces of evidence. Furthermore, it has been shown that samples taken on the location of attacks contain these toxins, while sites that have not been attacked do not show any signs of toxins in them. Even though it remains questionable if all witness reports are reliable sources of evidence, the symptoms recorded are typical for intoxication with trichothecenes. There was a number of ways in which trichothecenes were weaponized, such as dispersion as aerosol, smoke, droplets or dust from aircraft, missiles, handheld devices or artillery.
Safety guidelines in the food industry In 2000 a scientific opinion on nivalenol was issued by the Scientific Committee on Food (SCF). A temporary tolerable daily intake (t-TDI) of 0–0.7 μg/kg bw per day was issued after evaluation of the general toxicity as well as the haematoxicity and the immunotoxicity. This t-TDI was reaffirmed by the SCF in 2002. In 2010, the Japanese Food Safety Commission (FSCJ) issued a t-TDI of 0.4 μg/kg bw per day. Between 2001 and 2011, the European Food Safety Authority (EFSA) collected data from 15774 nivalenol occurrences in 18 European countries to be assessed. This led to the establishment of a TDI of 1.2 μg/kg bw per day. Nivalenol was in this studies not found to be genotoxic, but well haematotoxic and immunotoxic.
Structure and reactivity Nivalenol as part of the family of mycotoxins has the common structure which all members of this toxin family have. This includes the basic structure of a cyclohexene and a tetrahydropyran ring connected at C6 and C11. Additionally an ethyl-group connects the tetrahydropyran at C2 and C5 and a keto group is attached at the cyclohexene at C8. The epoxide group, responsible for the reactivity for most parts, is attached at C12 and C13 in the tetrahydropyran. Only the remaining groups at positions C3, C4, C7, C15 vary for the different mycotoxins. In case of nivalenol each of the four remaining groups is a substituted hydroxyl group which add up to the reactivity in presence of hydrophilic compounds or subgroups respectively thanks to their polar characteristics. In acidic medium the keto group is capable of reacting with a proton promoting polarity and reactivity as well. But altogether the epoxide group is crucial for the reactivity of the molecule.
Available forms Nivalenol, deoxynivalenol and T2-toxin are the three structural and similar synthesized mycotoxins naturally appearing in fungi (e.g. Fusarium).
Synthesis
… excerpt ends here. Continue reading the full article.
