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Chemical food safety

A/2011, 26.01.2011

Background paper for journalists

Chemical food safety is time and again in the focus of media attention, currently concerning dioxins in eggs and meat. The example is part of a series of issues which are publicly debated more or less emotionally and controversially. They include pesticide residues in food and vegetables, mycotoxins in pistachios, pyrrolizidine alkaloids in salad mixtures, acrylamide in various heat-treated foods, chemicals from packaging materials such as bisphenol A and semicarbazide, adulterations of foods with chemicals such as melamine in candies from China, glycol in wine and ingredients of genetically modified crops in foods and feeds, substances in foods which can cause damage to health out of a very diverse nature. Foods are complex mixtures of nutrients (proteins, carbohydrates, fats, minerals) and many natural accompanying substances. In addition they also contain low amounts of other substances, which reach the foods unintentionally as contaminations or occur at the production, storage and preparation of foods. On the other hand, certain substances such as technological auxiliaries or aroma substances are added to foods intentionally during production. Many of these substances, including the natural ingredients of foods, can become a human health risk under certain conditions. This background paper provides an overview of substances in foods.

Substances which can burden foods unintentionally include widespread environmental contaminants, substances from packaging materials which migrate into the foods, residues from veterinary medicinal products and pesticides. Toxic substances such as amygdalin in bitter almonds, solanine in potatoes and pepper, methyl eugenol and coumarin in spice plants and uranium or nitrate in drinking and mineral water occur naturally in foods. As a result of microbial spoilage during storage and transport of foods, bacterial toxins and moulds (mycotoxines) can develop. Fat oxidation leads at higher temperatures to peroxides, epoxides and polymerisation products of unsaturated fatty acids. The smoking and grilling of foods generates, amongst other things, low amounts of carcinogenic substances. Food additives which are intentionally added are not harmful if they are used in the approved concentrations.

Safe foods are a global topic against the backdrop of the international trade flows. The enormous progress in analytical chemistry permits the detection and quantification of increasingly small amounts of substances in foods. This permits the early detection of routes of exposure, and sources of contamination can be identified. These findings help to minimise risks already before they have a health-relevance for consumers.

Contaminants related to production and storage

Ready-to-eat foods are part of a modern lifestyle. The production of these foods may however involve the loss or reduction of essential nutrients. Substances can also change or new substances can arise which can possibly become a health risk. Many foods must be heat-treated to actually become edible, digestible and aromatic. This heating can, however, also have undesired consequences such as the loss of nutrients like vitamins, essential amino acids and unsaturated fatty acids. Harmful substances can develop, too. In the early 1970s carcinogenic substances developing during the heating of foods were discovered. Since then polycyclic aromatic carbohydrates (PACs) and heterocyclic aromatic amines have been known examples. A substance which was detected in foods more recently and whose risk assessment still raises a lot of questions is acrylamide.

Acrylamide

Acrylamide was detected for the first time in potato chips, French fries, roast and baked potatoes, bread and baked goods in 2002. Acrylamide develops in carbohydrate rich foods, which are processed or prepared at high temperatures, such as frying and baking at 120 degree Celsius plus. Acrylamide is a product of the so-called Maillard reaction between certain amino acids, mainly aspartic acid and reducing sugars such as glucose and fructose. This browning reaction and/or its products can be important for the sensorial properties (smell, taste) of the respective food. According to the classification system of the International Agency for Research on Cancer (IARC) acrylamide was classified as a "probable human carcinogen" (2A). The reactive product glycidamide developing in the metabolism of acrylamide has mutagenic properties. Epidemiological studies suggest with a certain evidence a carcinogenic effect of acrylamide. The relative risks were, however, low and the overall epidemiological evidence is not consistent. Further studies with a significantly improved recording of exposures are, therefore, necessary. Because of the wide dissemination of acrylamide in our foods and the comparatively high contents, the mechanisms of its formation must be better clarified in order to be able to lower the concentrations. Since acrylamide has a mutagenic and carcinogenic potential and no safe consumption amounts can be derived, possibilities need to be found in order to reduce the acrylamide concentration in foods as far as possible. The European Commission currently discusses the laying down of so-called guidance values in certain foods. After the detection of acrylamide the search for other potentially toxic substances which can develop during heat treatment in foods began. An EU-wide research programme (Heatox) has identified approximately 800 compounds of this kind which belong to different chemical classes. These compounds develop through the Maillard reaction or through lipid oxidation. Most of them have so far not been toxicologically studied. Whether so-called in silico tools for the determination of structure-action relationships will be successful here - as aimed at - to identify potentially toxic substances in foods through screening procedures or assess their risks is still open. The methodology permits a prioritisation of possible toxic substances for targeted testing. Under current viewpoints 3-monochloropropandiol (3-MCPD) and glycidol fatty acid esters as well as furan have become particularly significant.

Furan

Furan develops under heat from carbohydrates, ascorbic acid and multiple unsaturated fatty acids. IARC has classified furan as "possible human carcinogen" (2B). It can cause cancer in rats and mice. Its primary metabolite cis-2-butene-1,4-dial has mutagenic and cytotoxic properties. The risk potential of furan has not yet been fully clarified. There is, more particularly, a lack of knowledge on effects in relevant lower dosages. Data on the probability of occurrence of tumours in rats at doses of less than 2 mg/kg body weight are still needed. The lowest studied dose of 2 mg/kg body weight and day resulted in bile duct tumours in rats. Furthermore, the mechanisms underlying the mutagenic properties of the metabolic degradation products and their assessment are open. In an integrated EU-wide research project on the risk assessment of furan these aspects were clarified. To assess the exposure, the extent to which consumers come into contact with the substance data have by now been generated. For foods for infants and small children many content measurements on furan are available which permit an exposure assessment. Adults take furan more particularly up through toast and coffee from coffee vending machines. Since not all toxicological aspects are clarified, the current results cannot be reliably extrapolated at present to the situation of consumers. An attempt of risk characterisation with the assessment concept "Margin of Exposure" (MoE) would result, in particular for infants and small children, in a dimension which would not be classified as safe.

Glycidol and 3-MCPD fatty acid esters

Current analytical results confirm the already assumed occurrence of glycidol fatty acid esters in refined edible fats. Non-refined, native edible fats do not include these compounds. They develop, more particularly, during the so-called de-odourisation of vegetable fats, i.e. the removal of taste components perceived as unpleasant from the fats. During this refining process they are exposed to temperatures of up to 265°C. A safe exposure assessment is currently not yet possible. The development and validation of corresponding analytical methods are urgently required. Toxicological studies on glycidol fatty acid esters are currently not available. It is likewise not known whether and to what extent glycidol fatty acid esters are converted to glycidol during digestion. Glycidol has mutagenic and carcinogenic properties and was classified by IARC as "probably carcinogenic to humans" (2A). Pending the availability of corresponding study results, a risk assessment must, therefore, assume provisionally the worst case in hypothetic terms, i.e. a full transformation into glycidol. Alternatively, it would be necessary to carry out long-term toxicological studies with the corresponding fatty acid esters. For 3-MCPD fatty acid esters there is a similar problem. 3-MCPD causes renal tumours in rats. The way the tumours develop is not clarified in a satisfactory manner. 3-MCPD does not exhibit any mutagenic properties in vivo - unlike in the in vitro studies.

Trans fatty acids

Trans fatty acids are unsaturated fatty acids which are, however, similar to saturated fatty acids in terms of composition. They develop, more particularly, during the fat hardening of vegetable oils in the event of a partial hydration. The fat hardening provides the edible fats with the desired stability. Trans fatty acids occur in margarines and frying fat but also naturally in milk and butter. Foods with high contents of trans fatty acids contribute to an increase in the overall cholesterol level and the low density lipoproteins (LDL) and reduce the high density lipoprotein (HDL) levels in blood. Epidemiological studies suggest that there is a link between the trans fatty acid uptake and the risk of development of a coronary heart disease. EFSA assessed trans fatty acids in 2004. There is no statutory regulation for these compounds in Europe. Many food manufacturers have now developed products with a significantly reduced content of trans fatty acids or without any of them. During controls, imported goods have been discovered such as baked goods from Thailand in which Swedish control authorities detected contents of almost 40% in 2009.

Benzene

Benzene is known to cause cancer in humans. Traces of the compound were detected some time ago in certain beverages. It turned out that it can develop during processing and storage in soft drinks which contain the preservatives benzoic acid and ascorbic acid. The benzene contents in these beverages exceeded in some cases the maximum value of 1 μg/l (the WHO guideline value amounts to 10 μg/l) defined in the Drinking Water Ordinance. The health risk of benzene intake via soft drinks is difficult to assess. Since benzene is basically undesired in foodstuffs, appropriate technical measures are required in order to minimise the benzene content - for instance by changing the formulation or the production processes.

Contaminants from packaging materials

Substances with a low molecular weight can migrate from packaging materials to the foodstuff (migration) and hence be taken up by humans. The currently discussed examples are hormone-like substances (bisphenol A), plasticisers (phthalates) and printing ink components. The substance bisphenol A in particular has moved centre stage. It is used in the production of the plastics material, polycarbonate. The public debate focuses on exposure and action on the developing organism. EFSA reached the conclusion in an assessment in 2010 that new submitted data do not require any change in tolerable daily intake (TDI value) of 0.05 mg bisphenol A per kg body weight. In its expert report EFSA points out, however, that new data with so far unclear relevance for human health are available for the assessment of some studies on development toxicology relating to bisphenol A. These are studies on the influencing of the immune system, biochemical changes in the central nervous system and on the question in how far bisphenol A could contribute towards the sensitisation vis a vis breast cancer development. Based on this assessment the EU Commission has adopted a ban of polycarbonate in baby bottles for reasons of preventive health care.

Natural toxins

Natural toxins can be contained in many foods. They include algae toxins in mussels and other conchifera (marine biotoxins) and mycotoxins as secondary metabolites of moulds, such as aflatoxins, ochratoxins, trichothecene and patulin. Furthermore, toxins play an important role in plants; this applies to the different alkaloids (for instance pyrrolizidine and ergotamine alkaloids), hydrocyanic acid releasing glycosides such as amygdalin in bitter apricot kernels, certain hydrazines in fungi as well as coumarin in cassia cinnamon. Recently the assessment of ginkgolic acids in ginkgo leaf containing teas played a role. A particular toxicological interest is also directed to alkenyl benzenes such as methyl eugenol and estragole. As secondary metabolite with aroma properties they occur in certain spice plants in a high concentration. As isolated flavouring agent they may not be added to foods because some alkenyl benzenes have caused cancer in animal experiments. Methyl eugenol triggered liver tumours in rats and mice. This effect is also proven for safrol, estragole and isoeugenol. Furthermore alkenyl benzenes can cause mutations. According to the current findings the human health risk is difficult to assess. The Scientific Committee for Food (SCF) of the EU reached the conclusion that several alkenyl benzenes are mutagenic and carcinogenic and the limit value cannot be fixed. For that reason regulatory measures are difficult. On the other hand, it is argued that the health risk is comparatively low for the very reason that spice plants contain in addition to alkenyl benzenes also considerable amounts of polyphenols. Many of them are strong inhibitors of certain enzymes. A similar assessment is reached by a report of the European Scientific Cooperation (ESCO) working group "Botanicals and Botanical Preparations" in which several plants are assessed by way of example, including estragole-containing bitter fennel tea. As long as no new findings are available, it can for the time being only be recommended to reduce the amounts of intake.

Environmental contaminants and residues

The environmental contaminants and residues in foods include substances which have their origin above all in industrial processes and reach the food due to the environment and without intention. These can be heavy metals, polycyclic aromatic carbohydrates (PAC), polychlorinated biphenyls (PCBs) and dioxins. The latter accumulate in the food chain. In the current discussion increased dioxin contents in eggs and meat due to contaminated feed fats are discussed. Other examples for foods with increased dioxin contents were poultry meat and eggs in Belgium in 1999 and pork meat from Ireland at the end of 2008.

In addition, residues of substances play a role if they were used under a benefit aspect. These include pesticides and veterinary medicinal products. Residues of these substances and contaminants may not exceed prescribed maximum amounts in the respective food. The maximum amounts for many substances, including the maximum amounts for dioxins and for dioxin-like PCBs, are today regulated throughout the EU. Altogether the fixed maximum amounts for a substance should not exceed in the different foods the respectively valid "Acceptable Daily Intake" (ADI) or "Tolerable Daily Intake" (TDI). The European Commission currently proposes maximum levels for a total of four PACs in foods since the leading substance benzo(a)pyrene alone is no appropriate indicator for a PAC contamination. The four PACs are benzo(a)pyrene, benzo(a)anthracene, Benzo(b)fluoranthene and chrysene. In addition a provisional maximum amount for benzo(a)pyrene is to be complied with as a reference value. This management measure is the result of an EFSA position paper of 2008. Already banned substances are also found time and again in foods, such as nitrofurans, malachite green and chloramphenicol. This concerns in particular foods which are imported from non-European countries in which corresponding regulations do not exist or in which such substances are used although they are banned. Nicotine in dried ceps from China was in 2009 a so far unknown problem. Its origin continues to be unclarified. The discussion focuses on the use of nicotine as pesticide, a particular property of ceps to take up nicotine from cigarette smoke and a contamination through the use of the same facilities for tobacco plant and fungi drying. In addition, it is currently not excluded that nicotine is a natural ingredient of ceps. For the health risk assessment the nicotine source is without relevance. It might, however, be relevant for the possible definition of maximum amounts.

Allergens in foods

Food allergies are over sensitivities to certain proteins. So far more than 160 foods have been identified which can cause allergic reactions. There are essentially eight food categories which account for 90% of all food allergies. A particular importance is attributed to milk, eggs, fish and different nuts. In this connection the question of a threshold dose arises, i.e. the lowest dose which can still cause an allergic reaction in highly sensitive people. At present there is consensus that such threshold doses cannot yet be reliably laid down for allergy causing proteins. Sensitive people should simply strictly avoid the relevant proteins. The necessary labelling is currently regulated for 14 food ingredients (Directive 2007/68/EC). However, unintentional transfer of components to foods, for instance during production and transport, is not regulated. At present processes for a rapid detection of proteins are being developed. For the fixing of threshold doses there is need for research.

Genetically modified organisms (GMOs)

So far conventional crops were in most cases genetically modified in order to bring about a resistance to herbicides and/or protection from insect attacks. Further goals are an improved nutrient profile and a higher resistance to plant diseases. With the approval for herbicide tolerant soy beans the import of genetically modified plants to produce foods and feeds to the EU was authorised for the first time in 1996. At present several corn, cotton, soy bean, rape seed and sugar beet species as well as products made from them are approved. For the cultivation within the EU only the corn MON810 has so far received an authorisation. In Germany this corn may not, however, be cultivated due to the "suspended authorisation". Globally almost 140 million hectares of arable land are likely to be currently cultivated with genetically modified crops such as soy beans, corn, cotton, potatoes and tomatoes. These crops contain in their genome artificially introduced genes which result in the development of new proteins and other ingredients or changed contents of naturally occurring ingredients. The selectively induced but possibly also unintentional changes can involve health risks. There is, for instance, a possibility that metabolic pathways are changed in such a way that the plant develops naturally occurring toxicologically relevant ingredients in larger amounts. For this reason foods and feeds from genetically modified plants may only be placed on the market after a safety assessment by EFSA with the involvement of the EU Member States. The risk assessment is carried out by means of molecular biological, chemical analytical and toxicological methods by comparison with corresponding traditional products.

Food additives

The food additives include, amongst other things, preservatives, anti-oxidants, emulsifiers, colorants and sweeteners. They are only authorised after a comprehensive risk assessment. In this connection an acceptable daily intake, the ADI value, is derived. Based on this value maximum amounts can be fixed for food additives. They ensure that the total uptake of additives from different foods does not result in an exceeding of the ADI value. Moreover, maximum amounts are to be in the range of the lowest amount which is technologically possible. Aromatic substances have a special position between additives and natural ingredients. They are added on the one hand to foods for the purpose of aromatisation but they often also occur naturally in foods as flavouring ingredients. Since the group of aromas is extensive with approximately 2,700 compounds, a risk assessment of each individual substance is not possible. At present EFSA, therefore, assesses groups of chemically allied compounds. Aromas are usually only used in low concentrations. The assessment of the substance groups should focus primarily on possible mutagenic and carcinogenic properties.

Food safety and regulatory aspects

Foods which are not safe may not be placed on the market. This is generally regulated in Article 14 of the "Base" Regulation (EC) No. 178/2000. In the event of decisions about whether a food is harmful, its probable impact not only on the health of the consumer needs to be taken into account but also its impact on the health of the following generations. Possible cumulative toxic effects and the particular health sensitivity of certain consumer groups need to be taken into account. Unlike for medicinal products the possible risks are not compensated by a benefit possibly offsetting it. The goals of effective consumer protection are health protection, protection from adulteration and factual information.

Consumer protection in the field of food safety is carried out through an independent scientific risk assessment, the implementation of the resulting measures as well as appropriate risk communication. These are tasks which are subject to state supervision. In the first central step a possible health risk is assessed in accordance with internationally applicable methods according to the state of science. The corresponding basis is provided as a rule by animal experiment tests to identify toxic or at least undesired effects on the organism as well as the establishment of the highest dose which does not yet cause any toxicologically relevant effect. This dose without effect is referred to as "No Observed Effect Level".

Both the conduct of the test and the assessment of the test results, the derived No Observed Effect dose and the latter's transfer to humans are uncertainties whose dimension is not known individually. For these reasons the absolute innoxiousness of a food ingredient or additive cannot be exactly proven and the degree of certainty cannot be safely stated. Based on the highest dose without effect, upper limits are derived by extrapolation in respect of an acceptable or tolerable area for humans for the definition of intake amounts without health risk of a substance. This derivation of so-called ADI or TDI values is as a rule carried out by competent scientific bodies such as the "Joint FAO/WHO Expert Committee on Food Additives" (JECFA) and the Scientific Panels of EFSA. These ADI and TDI values do not have a legally binding character but they continue to serve as recognised basis for the establishment of legally binding maximum amounts in foods which are defined within the framework of the legal provisions.

The fixing of maximum amounts is no longer part of the food toxicological risk assessment but is a measure of risk management. In certain cases it is not possible to assume ADI or TDI values but other aspects such as detection limits or feasibility must be used. ADI and TDI values depend on the current state of knowledge on the toxicology of the respective substance and may change in the course of time with new findings as was frequently the case in the past. If a risk assessment results in indications or suspicions of uncertainties and health risks, further studies must be carried out for clarification purposes. However, if there is clear proof, risk management may decide about the measures to be carried out. As opposed to the strictly scientific risk assessment, risk management involves, amongst others, social policy and economic aspects to assess the measures in terms of their appropriateness and efficiency. The institutional organisations of risk assessment, risk communication and risk management are differently structured in the EU Member States. In some Member States all three fields of activity are combined, whereas other states prefer a functional or institutional division of labour. In Germany the Federal Institute for Risk Assessment (BfR) has the task of assessing health risks on a scientific basis and to communicate these risks. Risk management, i.e. measures to deal with these health risks, is the responsibility of the Federal Ministry for Food, Agriculture and Consumer Protection (BMELV) and the Federal Agency for Consumer Protection and Food Safety (BVL) as well as the public authorities of the Federal Lander.

About BfR

The Federal Institute for Risk Assessment (BfR) is a scientific institution within the portfolio of the Federal Ministry of Food, Agriculture and Consumer Protection (BMELV). It advises the Federal Government and Federal Laender on questions of food, chemical and product safety. BfR engages in own research on topics that are closely linked to its assessment tasks.

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