TOXICOLOGY AND TOXINOLOGY OF MYCOTOXINS IN FOODS
Location: Toxicology and Mycotoxin Research
| Bulder, Astrid - |
| Wu, Felicia - |
| Resnik, Silvia - |
| Kpodo, Kafui - |
| Arcella, Davide - |
| Carrington, Clark - |
| Wolterink, Gerrit - |
| Bolger, Mike - |
Submitted to: World Health Organization
Publication Type: Monograph
Publication Acceptance Date: December 1, 2011
Publication Date: March 15, 2012
Citation: Bulder, A.S., Arcella, D., Bolger, M., Carrington, C., Kpodo, K., Resnik, S.,Riley, R.T., Wolterink, G., Wu, F. 2012. Fumonisins. In: Safety evaluation of certain food additives and contaminants. Geneva. World Health Organization. WHO Food Additives Series. 65:325-794.
Interpretive Summary: Abstract - no summary required.
Fumonisins were previously evaluated by the fifty-sixth meeting of the Committee. The Committee established a group PMTDI for fumonisins B1 (FB1), B2 (FB2) and B3 (FB3), alone or in combination, of 2 µg/kg bw on the basis of the NOAEL of 0.2 mg/kg bw per day for kidney toxicity and application of a safety factor of 100. All of the estimates of exposure to FB1 based on the available data on national consumption were well below the group PMTDI, even when exposure estimates for FB1 were increased by 40% to account for the presence of FB2 and FB3. For the current evaluation, the Committee reviewed all relevant studies performed on fumonisins since 2001.
The B series of the fumonisins, including FB1 (CAS No. 116355-83-0), FB2 (CAS No. 116355-84-1), FB3 (CAS No. 136379-59-4) and FB4 (CAS No. 136379-60-7), the major forms found in food, was described previously by the Committee. Since then, the number of known fumonisin analogues has greatly increased. The analogues can be classified into four main groups, A, B, C and P, which contain two tricarballylic acid moieties. Members of the series FBX are different from these, because they are esterified by other carboxylic acids, such as cis-aconitic acid, oxalylsuccinic acid and oxalylfumaric acid. New fumonisins recently described have their 19- or 20-carbon aminopolyhydroxyalkyl chain esterified by fatty acids, such as palmitic acid, linoleic acid and oleic acid (0.1% of the FB1 concentration).
The FB1 toxin has 10 chiral centres; theoretically, therefore, 1024 stereoisomers can be produced. From culture material, currently 28 FB1 isomers have been isolated and characterized (2.8% of the possible fumonisins). The identification and absolute configuration of the stereoisomers 3-epi-FB3 and 3-epi-FB4 have been elucidated since the previous evaluation. The hydrolysis of the tricarballylic esters at C-14 and C-15 gives rise to partially hydrolysed fumonisin B (PHFB) or totally hydrolysed fumonisin B (HFB) in food.
Fusarium verticillioides and F. proliferatum are the main sources of fumonisins in maize, and both can produce series B and C analogues. Fusarium proliferatum can also produce series P analogues. Recent occurrence data have shown that Aspergillus niger, a common fungus growing on grapes, green coffee beans, onions, mango, corn and other cereals, peanuts and dried fruits, is able to produce FB2, FB4 and FB6. Some strains of Fusarium oxysporum, a worldwide fungal contaminant, also produce fumonisin C analogues.
The term “hidden fumonisin” is used only for non-covalently bound derivatives, which are formed through an interaction between fumonisins and matrix macroconstituents or physical entrapment. “Bound fumonisin” refers only to those compounds that involve covalent linkages between the analyte and the matrix constituents. The linkages may involve the fumonisin free amino group or the carboxylic moieties. A few studies conducted with a limited number of samples show that substantial amounts of hidden or bound fumonisins may be present in raw maize, and commonly used analytical methods are not able to detect their occurrence.
Fumonisins were on the agenda of the present meeting at the request of the Fourth Session of the Codex Committee on Contaminants in Food, which asked the Committee to update the toxicological evaluation taking into account all new data, to evaluate potential adverse health effects of co-occurrence of fumonisins with other mycotoxins, in particular aflatoxins in maize and cereals, to evaluate the occurrence in feed and carry-over to address public health relevance, to evaluate recent occurrence data in food (including bound fumonisins in processed products), to perform an exposure assessment and to perform an impact assessment of different hypothetical maximum levels in different products.
The Committee reviewed new studies on metabolism and toxicokinetics, mechanisms of toxicity, acute, short-term and long-term toxicity, genotoxicity, reproduction and developmental toxicity of fumonisins, as well as combination toxicity with other mycotoxins. New information on occurrence, processing, prevention and control, and dietary exposure was considered. Also, the impact of several hypothetical maximum levels in maize products was evaluated.