Appropriateness to set a group health‐based guidance value for fumonisins and their modified forms

Abstract

The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for fumonisin B 1 (FB 1 ) of 1.0 lg/kg body weight (bw) per day based on increased incidence of megalocytic hepatocytes found in a chronic study with mice. The CONTAM Panel considered the limited data available on toxicity and mode of action and structural similarities of FB 2-6 and found it appropriate to include FB 2 , FB 3 and FB 4 in a group TDI with FB 1 . Modified forms of FBs are phase I and phase II metabolites formed in fungi, infested plants or farm animals. Modified forms also arise from food or feed processing, and include covalent adducts with matrix constituents. Non-covalently bound forms are not considered as modified forms. Modified forms of FBs identified are hydrolysed FB 1-4 (HFB 1-4 ), partially hydrolysed FB 1-2 (pHFB 1-2 ), N-(carboxymethyl)-FB 1-3 (NCM-FB 1-3 ), N-(1deoxy-D-fructos-1-yl)-FB 1 (NDF-FB 1 ), O-fatty acyl FB 1 , N-fatty acyl FB 1 and N-palmitoyl-HFB 1 . HFB 1 , pHFB 1 , NCM-FB 1 and NDF-FB 1 show a similar toxicological profile but are less potent than FB 1 . Although in vitro data shows that N-fatty acyl FBs are more toxic in vitro than FB 1 , no in vivo data were available for N-fatty acyl FBs and O-fatty acyl FBs. The CONTAM Panel concluded that it was not appropriate to include modified FBs in the group TDI for FB 1-4 . The uncertainty associated with the present assessment is high, but could be reduced provided more data are made available on occurrence, toxicokinetics and toxicity of FB 2-6 and modified forms of FB 1-4 . and Alexander J, 2018. Scientific opinion on the appropriateness to set a group health-based guidance value for fumonisins and their modified forms. EFSA Journal 2018;16(2):5172, 75 pp. https://doi.This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made.The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. HBGV for fumonisins and their modified forms www.efsa.europa.eu/efsajournal 2 EFSA Journal 2018;16(2):5172 HBGV for fumonisins and their modified forms www.efsa.europa.eu/efsajournal 3 EFSA Journal 2018;16(2):5172Although FBs are poorly absorbed, unchanged FBs excreted into urine have been used as a biomarker of exposure in humans. In animal studies changes in sphinganine (Sa) and sphingosine (So) and the Sa/So ratio can be determined in urine following FB exposure. A dose related increase in the sphinganine 1-phosphate (Sa 1-P)/sphingosine 1-phosphate (So 1-P) ratio in blood spots which correlated with urinary FB 1 levels has been reported in human studies. This result is consistent with fumonisin inhibition of CerS in humans.Toxicity studies deal mainly with effects of FB 1 , but FB 2-4 are considered as having similar toxicological profiles and potencies. FB 1 is considered not to be acutely toxic. In repeated dose st...

Dietary Fumonisin and Growth Impairment in Children and Animals: A Review

“…It should be noted that fumonisin exposure in natural settings for both animals and humans is not purified, and in animal studies the adverse effects on feed consumption and weight gain are often concurrent with other adverse effects such as hepatotoxicity and renal toxicity. The toxicity of fumonisins in laboratory and farm animals has been reviewed extensively (JECFA, , ; Knutsen et al., ; WHO, ). The following is not an all‐inclusive review, as these documents have previously done; but is intended to highlight the specific relationship between fumonisin intake and growth impairment in animals.…”

“…Several recent studies have shown that the residual hydrolyzed forms of fumonisin formed during alkaline hydrolysis are less toxic in animal feeding studies (Grenier et al., ; Voss, Riley, Moore, & Burns, ; Voss, Ryu, Jackson, Riley, & Gelineau‐van Waes, ). These studies and others have been reviewed in the recently published Scientific Opinion of the EFSA (Knutsen et al., ). Dombrink‐Kurtzman, Dvorak, Barron, and Rooney () reported that alkaline treatment can significantly reduce the amount of FB 1 in the process of making tortillas.…”

“…Several recent studies have shown that the residual hydrolyzed forms of fumonisin are less toxic in animal feeding studies. These studies have been extensively reviewed in the recently published Scientific Opinion of the EFSA (Knutsen et al., ). Appropriate to rural settings, hand‐sorting, cleaning, flotation and dehulling of maize kernels, proper storage conditions, and insect control have also proven effective intervention strategies in reducing fumonisin (Fandohan et al., ; Matumba, Van Poucke, Njumbe Ediage, Jacobs, & De Saeger, ; van der Westhuizen et al., ).…”

“…The PMTDI established in 2001 was retained in two subsequent JECFA evaluations (JECFA, , ). A recent evaluation by the European Food Safety Authority (EFSA; Knutsen et al., ) has proposed a group TDI of 1 μg/kg bw/d based on increased incidence of megalocytic hepatocytes found in a chronic study with mice (Bondy et al., ).…”

“…Fumonisin exposure in Tanzania is the highest in rural areas, particularly in infants and young children who consume large amounts of maize‐based foods relative to their body weights (Kimanya et al., ). Fumonisin intake by women of reproductive age in countries where maize is a dietary staple can also be very high (Riley et al., ; Torres et al., ), often exceeding the recommended TDIs proposed by JECFA and EFSA (JECFA, ; Knutsen et al., ), suggesting the potential for effects on fetal and postpartum growth. Therefore, it is critical to understand the impact of fumonisin on fetal outcomes and children's health and growth.…”