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Natural Toxins: Risks, Regulations and the Analytical Situation in Europe

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Natural Toxins: Risks, Regulations and the Analytical Situation in Europe Anal Bioanal Chem (2004) 378 : 1152–1160 1152 DOI 10.1007/s00216-003-2373-4 REVIEW Hans P. van Egmond Natural toxins: risks, regulations and the analytical situation in Europe Received: 25 July 2003 / Revised: 15 October 2003 / Accepted: 27 October 2003 / Published online: 13 December 2003 © Springer-Verlag 2003 Abstract Natural toxins in food and feed are considered pean context are now directed towards significantly im- important food safety issues of growing concern, in par- proving this situation, and techniques such as liquid chro- ticular mycotoxins, phycotoxins and plant toxins. Most matography–mass spectroscopy offer promise in this re- scientific developments have occurred in the past few spect. Both the working group on biotoxins of the Euro- decades in the area of mycotoxins. Formal health risk as- pean Standardization Committee and the network of Na- sessments have been carried out by the Joint Expert Com- tional Reference Laboratories for Marine Biotoxins have mittee on Food Additives of the World Health Organiza- taken up responsibilities here. The plant toxins are a cate- tion and the Food and Agriculture Organization. Limits gory of natural toxins, where the situation is the least de- and regulations for mycotoxins in food and feed have veloped with respect to regulations, validated methods of been established in many countries, including practically analysis and reference materials. Yet, their occurrence in a all European countries. An array of (formally validated) wide range of consumable plant species demands the at- analytical methods and (certified) reference materials have tention of the analytical community. become available. Several European research projects, funded by the European Commission and supported by the Keywords Natural toxin · Mycotoxin · Phycotoxin · European Standardization Committee, have significantly Plant toxin · Analysis · Reference material contributed to this development. Quantitative methods of analysis for mycotoxins often make use of immunoaffin- ity cleanup with liquid chromatographic or gas chromato- Introduction graphic separation techniques in combination with vari- ous types of detectors, including mass spectroscopy. For Over recent years there has been an increased scientific screening purposes (bio)sensor-based techniques are among interest in natural toxins in food and feed. The occurrence the promising newcomers. For the phycotoxins the situa- of these harmful organic compounds of natural origin is of tion is less advanced. Formal risk assessments by authori- growing concern to human health. Some natural toxins tative international bodies have not been carried out. are extremely potent acute toxins (e.g. botulin) or are Methods of analysis, formally validated according to in- strong carcinogens (e.g. aflatoxins). ternationally harmonized protocols, are scarce and animal On the basis of their origin the natural toxins can be di- testing still plays a key role in official methodology. The vided into five main categories: development of the analytical methodology is partly ham- – Mycotoxins: toxins produced by fungi. Most have rela- pered by the limited availability of certain reliable cali- tively small molecular weights, and they are usually brants and reference materials, although this situation is heat-stable. Mycotoxins that are significant in terms of gradually improving. New regulations in the European toxicity and occurrence include the aflatoxins, ochra- Union have increased the pressure to develop and validate toxins, trichothecenes, patulin, fumonisins and zear- chemical methods of analysis. Joint efforts in the Euro- alenone. – Bacterial toxins: toxins produced by bacteria. Many bacterial toxins are proteins, which are not heat-stable. Some well-known bacterial toxins are botulin, Staphy- H. P. van Egmond (✉) lococcus aureus enterotoxin and Bacillus cereus en- Laboratory for Food and Residue Analyses, terotoxin. National Institute for Public Health and the Environment (RIVM), – Phycotoxins: toxins produced by algae that, through P.O. Box 1, 3720 BA Bilthoven, The Netherlands feed chains, end up in fishery products, such as shell- e-mail: [email protected] fish. Some phycotoxins of significant human health 1153 concern include the paralytic shellfish poisoning toxins, a scientific advisory body of the WHO and the Food and the diarrhoeic shellfish poisoning toxins and the am- Agriculture Organization (FAO), has recently evaluated nesic shellfish poisoning toxins. their hazard [2, 3]. JECFA provides a mechanism for as- – Plant toxins (also named phytotoxins): toxins that are sessing the toxicity of additives, veterinary drug residues produced by edible plant species. Some play a role in and contaminants. Safety evaluation of contaminants in- the defence mechanism of plants against attacks of in- corporates various steps in a formal health risk assessment sects and fungi. Examples are the potato glycoalkaloids approach. The 56th session of JECFA was specifically di- and toxins occurring in herbs, such as pyrrolizidine al- rected to mycotoxins. The report addressed several con- kaloids, and anisatin in certain varieties of star anise. cerns about each mycotoxin: explanation of the myco- – Zootoxins: toxins produced by animals, e.g. snakes, toxin, absorption through excretion, toxicological studies scorpions and certain frogs. Zootoxins are generally of and final evaluation. It is interesting to note that, along lesser significance to human health by oral exposure, with the mycotoxin evaluations, JECFA put forward gen- although exceptions occur, such as bufotoxin, a toxin eral considerations on analytical methods, sampling, asso- excreted by Bufo marinus. Licking the head of this toad ciated intake issues and control [2, 3]. In particular, good (a dangerous practice of drug addicts in the Nether- surveillance data should be generated using validated an- lands) leads to hallucinations. alytical methods and reference materials to ensure reliable results. Methods used should be validated through collab- The first three mentioned categories of natural toxins are orative studies of analytical performance; however, the in fact bio-contaminants. They are produced by microor- committee recognized that it may not always be possible ganisms and may contaminate food and food products. to use a validated method due to expense or an official This is not the case with the last two categories, which are method being irreconcilable to a particular toxin–matrix inherent components of plants or animals. This article will combination. The committee also stressed the importance be restricted to the mycotoxins, the phycotoxins and the of laboratories participating in interlaboratory comparison plant toxins. These three categories of chemical hazards studies to ensure analytical quality assurance. are characterized by the World Health Organization In Europe various organizations are involved with risk (WHO) as significant sources of food-borne illnesses [1]. assessment of mycotoxins: Of these categories, most research has been carried out on the mycotoxins, which are currently a major food safety – Both the Scientific Committee on Food (SCF) and the issue. Problems with mycotoxins are more severe than Scientific Committee on Animal Nutrition (SCAN) of with the other categories of toxins, due to the widespread the EC have regularly expressed scientific opinions about consumption of goods being contaminated. Various net- risks associated with the occurrence of mycotoxins in works of scientists are active, and the European Commis- food or animal feed, respectively. For example, SCAN sion (EC) is a major sponsor of European mycotoxin re- recently updated its opinion on undesirable substances search projects. Research on phycotoxins (in particular in animal feed [4], which included several mycotoxins the marine biotoxins) is of growing significance in Eu- for which the EC might establish new regulations in the rope where problems regularly lead to closures of shell- near future. fish harvesting areas. Also here networking exists in Eu- – The newly formed Scientific Panel on Contaminants in rope, and EC-funded research activities take place, but to the Food Chain of the recently established European a lesser extent than for the mycotoxins. Investigations on Food Safety Authority (EFSA) is specifically charged plant toxins still seem to have a lower priority in Euro- (among other issues) with mycotoxins. pean food safety research activities, and scientific net- –Efforts to assess exposure, one of the main ingredients working is in its infancy here. of risk assessment, are undertaken within SCOOP (SCOOP: Scientific Cooperation on Questions relating to Food) projects, funded by the EC. SCOOP projects Mycotoxins on mycotoxins are targeted to make the best estimates of intake of these toxins by EU inhabitants. In the 1990s Risks and regulations these activities resulted in a report on the exposure as- sessment of aflatoxins [5]; later SCOOP reports for Mycotoxins are secondary metabolites of fungi, which are several other mycotoxins followed (for ochratoxin A, capable of producing acute toxic, carcinogenic, muta- patulin, trichothecenes, fumonisins and zearalenone) genic, teratogenic, immunotoxic and oestrogenic effects [6, 7, 8]. SCOOP data were used by the SCF for its on animals at the level of exposure. Biological conversion evaluation and advisory work on the risks to public products of mycotoxins are also referred to as mycotox- health arising from dietary exposure to certain myco-
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