Elsevier

Toxicology Letters

Volume 153, Issue 1, 10 October 2004, Pages 91-98
Toxicology Letters

Combined toxic effects of mycotoxins

https://doi.org/10.1016/j.toxlet.2004.04.046Get rights and content

Abstract

It is known for many years that several food items, derived from plants infected by fungi in the field during growing of the plant or during harvest and storage of the food item, can contain concomitantly different mycotoxins. As these combined mycotoxins occur simultaneously in the food item, consumption of the food will lead to a combined intake depending on the absorption rates of the different mycotoxins. Therefore, the question is justified whether such a combined intake of mycotoxins would lead to a possible higher risk for adverse health effects than the intake of one of these mycotoxins alone. It will be dealt with on the basis of some practical cases of such combined intake of mycotoxins of which research data are available. This is the case for citrinin and ochratoxin A, but as the workshop focuses on trichotecenes and so this paper concentrates on these. When the mycotoxins are of similar structure and of the same species, or of the same families, it is likely to expect that the mode of action of the mycotoxins and or the toxicity profiles will be quite similar. This indicates that such related mycotoxins are likely to exert only additive effects, which is important to know. In terms of risk assessment, these mycotoxins could be dealt with by establishing a group daily tolerable intake (TDI) or a provisional tolerable weekly intake (PTWI). In terms of risk assessment those mycotoxins which interact in synergistic manner are of more concern. It is concluded that, at present tools are not fully developed to establish the type of interaction or whether there is any interaction at all.

Introduction

Several mycotoxins, either from the same or from different fungal species, occur simultaneously in plant products. However, its implication for food safety assessment is generally not known, as there is relatively little information on the interaction between concomitantly occurring mycotoxins and the consequence for the toxicity. There are several combinations of mycotoxins that frequently occur as established in analytical–chemical monitoring programs. These combinations are summarised in Table 1.

Section snippets

Mechanistic interactions of mycotoxins; theory

The data on combined toxic effects of mycotoxins are generally limited, particularly with respect to trichothecenes. Most data available are related to ochratoxin A (OTA), which will be discussed later. The available data show that adequate studies to establish antagonistic, additive or synergistic effects after combined exposure to mycotoxins are rare, and it is known that the issue of combined toxicity is very complicated. In general, a lot of such studies are difficult to interpret. When a

Experimental studies on interaction between different mycotoxins

When the data available from toxicity studies in which animals were exposed to several mycotoxins concomitantly is reviewed, it is striking that there are not so many studies performed. Particularly, there is not much information on trichothecenes. Therefore, the example of the combination of OTA and citrinin is outlined here, of which there are relatively more studies. The outcome of these studies can also be compared with what would be predicted on the basis of the previously described

Interaction studies involving trichothecenes

At present, there are a few studies in which a combination of trichothecenes and other mycotoxins have been investigated. Morris et al. (1999) performed feeding studies in young turkeys which were administered 20 mg DON or 100 mg moniliformin (M) alone or in combination. No toxic synergy was observed in this 21-day study. Furthermore, in weaner pigs, combined administration of fumonisin, DON, T-2 together with OTA, in quantities expected to be present in feeds of central European origin,

Concluding remarks

A theoretical consideration on the basis of cellular modes of actions of the mycotoxins would be very useful as a starting point to screen certain combinations for their possible synergistic or additive effects. Subsequently, a higher priority for further special research should then be given to those combinations of mycotoxins that are expected to include synergistic effects. Additive effects, which seem to be the case for most combinations of trichothecenes, could be implemented within the

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