Principle

As part of their natural protection mechanism to survive adverse growing conditions, insect attack or other kinds of hostile environment, plants or fungi can naturally produce a variety of toxic chemicals. These can be toxic when consumed by humans, and in some cases be mutagenic or carcinogenic. The manufacturer needs to be aware of the potential risk of plant toxins and have appropriate management systems in place to minimise the risk to consumers of the food products they produce. Great care should be taken (a) to formulate foods to avoid, wherever possible, inclusion of major serious allergens as ingredients, (b) to provide appropriate warning to potential purchasers of the presence of a major serious allergen in a product and (c) to organise production, production schedules and cleaning procedures to prevent cross‐contamination of products by ‘foreign’ allergens.

Plant Toxins

8.1 Naturally occurring plant‐related toxins include oxalic acid and prussic acid. Those produced by fungi and moulds include alternaria, ergot and mycotoxins. Algal toxins, which can be concentrated in seafood, include okadaic acid and domoic acid. As an example, solanine and chaconine are glycoalkaloids naturally produced by potatoes as a defence mechanism against insects, pathogens and herbivores on potato tubers exposed to light. The associated ‘greening’ of the tuber, caused by chlorophyll production, suggests increased levels of glycoalkaloid within the potato, meaning such potato tubers are not fit for human consumption. At the product development stage all plant‐derived ingredients must be considered for the potential of these naturally occurring toxins to cause acute or chronic harm to consumers and appropriate controls must be in place to minimise harm to the consumer. These controls may need to cover growing, harvest, storage, transport or processing conditions.

The examples used in this chapter are not designed to be exhaustive, but give an insight into the manufacturer’s obligation to understand the potential for natural toxins to occur in the raw ingredients or products they handle and process, and confirm that the onus is on the manufacturer to ensure that appropriate controls are in place to safeguard the consumer from harm. The manufacturer must have appropriate food safety risk assessment processes in place, e.g. hazard analysis critical control point (HACCP; see Chapter 3), that consider these natural toxins if they are likely to occur in ingredients or products that are to be processed and how the risk of harm to consumers can be mitigated. Raw beans, for example, contain lectin, a toxic agent that is inactivated by appropriate processing conditions. Manufacturing processes for products that contain beans therefore must be developed to inhibit lectin activity to ensure the food is then safe to consume.

8.2 Mutagens are physical or chemical agents that change the genetic material of an individual and in so doing increase the number of genetic mutations that occur in its body. Naturally occurring mutagens are ubiquitous in processed foods, particularly cooked and smoked foods. It is the responsibility of a manufacturer to be aware of the potential presence of these mutagens and to ensure that appropriate procurement procedures are in place to minimise the risk to consumers. As many mutagens can cause mutations that can lead to cancer, these particular agents are also classified as carcinogens. Again this topic is explored through an example rather than giving an exhaustive account within this chapter. Acrylamide is an example of a carginogenic mutagen that can be found in some fried, roasted or baked carbohydrate‐based foods, or more generally foods heated to above 120 °C. Manufacturers who undertake these process steps with the carbohydrate‐based foods they manufacture should undertake a specific acrylamide risk assessment in order to develop risk‐based controls that are effectively implemented and routinely verified to ensure their efficacy. A minority of mutagenic processing by‐products have legal limits, but in all cases the underlying principle of risk management is an ALARA (As Low As Reasonably Achievable) approach.

The senior management of the manufacturing organisation should ensure that adequate resources are committed to the development of a comprehensive food safety management system (FSMS) that is designed, documented, implemented and reviewed and so furnished with personnel, equipment and resources to ensure that all potential food safety hazards are adequately controlled and mitigated (see Chapter 3).

Adverse Reactions to Foods

8.3 More widespread adverse reactions to foods and food ingredients not only include allergic reactions, but also reactions such as functional food intolerance due to enzymatic abnormalities (enzymopathy) in individuals, e.g. lactase deficiency leading to lactose intolerance, structural intolerance affecting the gastrointestinal tract (e.g. transport defects in the gut, fructose intolerance) and pharmacological reactions to non‐proteinaceous substances (e.g. colourants (tartrazine), preservatives (benzoates or sorbates)), sodium glutamate or amines due to excessive intake from food rich in tyramine, tryptamine, histamine and serotonin. Histamine, for example, is said to play a role in migraines in susceptible individuals. Histamine‐rich and histamine‐releasing foods include fermented foods, processed meats, wine, beer, cheese, chocolate and dried fruits such as apricots.

8.4 The United Kingdom (UK) Food Standards Agency (FSA) has highlighted six food colours that have been associated with intolerance and hyperactivity in young children. These are sunset yellow FCF (E110), quinoline yellow (E104), carmoisine (E122), allura red (E129), tartrazine (E102) and ponceau 4R (E124). A voluntary ban has been introduced, and manufacturers have been asked to reformulate products to remove these colourants. In respect of these six colours, the EU Regulation No. 1333/2008¹ on food additives requires that, as of 20 July 2010, for all foods that contain these colours a warning is included on the packaging to the effect that the colours may have an adverse effect on activity and attention in children. The FSA provide further guidance on the labelling associated with these colours.² Annex II on EU Regulation No. 1338/2008 was published as Commission Regulation (EU) No. 1129/2011, entered into force on 2 December 2011 and applied from 1 June 2013. Regulation (EU) No. 232/2012, which came into force on 23 May 2012 and applied from 1 June 2013, amends Annex II to restrict the use and levels for three colours: quinoline yellow, sunset yellow and ponceau 4R. The levels of these colours are now restricted in a number of food categories, including soft drinks, confectionery, sauces and seasonings and in some cases (e.g. ponceau 4R in sauces and seasonings) no longer permitted. The Regulation includes a maximum use level of 20 mg/l for sunset yellow in soft drinks. Exemptions with regard to ‘warning’ labelling are in force in the UK, e.g. for alcoholic drinks above an alcohol content of 1.2%.

8.5 About 1–2% of adults and between 5 and 7% of children are thought to suffer from some type of immunoglobulin E (IgE)‐mediated food allergy. The higher incidence of allergies in infants is due to allergy to cow’s milk, which children generally grow out of by school age.³ Individuals can experience both immunological and non‐immunological adverse reactions to food. Adverse reactions to food that have an immunological basis are termed ‘food allergies’ and include those that involve IgE‐mediated reactions and the auto‐immune conditions requiring gluten avoidance, coeliac disease, which is thought to have a cellular immune mechanism. This means that the problems associated with food allergens are part of a wider problem that includes all adverse reactions to foods. These include reactions that result from microbial and chemical food poisoning, psychological aversions, behaviour change and specific non‐allergenic responses. It is important for the manufacturer to understand that these immune‐mediated (allergic) and non‐immune‐mediated reactions exist and that they need to demonstrate that they have done all that could reasonably be expected to consider the health impacts of the food products they manufacture on their consumers.

In total over 170 foods have been documented in the scientific literature as causing allergic reactions. However, most plant allergens belong to a small number of protein superfamilies. Food allergy is a complex topic and multiple factors influence which individuals may exhibit an allergic reaction to a given food. Scientific papers report that these include nationality, dietary habits and hereditary or environmental factors.⁴ As food can be sold across the world it is a requirement for food manufacturers to understand in detail the issues that can arise in a particular export market with regard to labelling of foods or food ingredients that have been identified as being associated with an allergic response in sensitive individuals. Cross‐reactivity may occur where an individual is allergic to a protein in one food, which resembles a protein found in something else e.g. individuals sensitised to latex (rubber) can have a similar response to some proteins present in kiwi fruit, banana or avocado, whilst those sensitised to peanut many have an allergic response to lupin flour.

Proteins that cause an adverse response in susceptible individuals can be divided into groups or families. The prolamin superfamily of proteins, produced as a response to an insect attack, is associated with cereals and the cupin superfamily is associated with tree nuts, seeds and legumes such as chickpeas. The profilin family (e.g. melon) and pathogenesis‐related (PR) proteins are not families, but are a group of proteins produced as part of the plant defence mechanism. These latter proteins can be found, for example, in celery and stone fruits. There is a differentiation within the law for the supply chain controls that are required. As outlined there are foods, ingredients or proteins known to cause an adverse reaction in susceptible individuals. More specifically there are food ingredients and foods themselves known to cause an allergic response in susceptible individuals, and these foods are required to carry allergen labelling by law. The specific legislative requirements of which foods require allergen labelling and which do not differ from country to country.

8.6 Manufacturers need to make themselves more aware of the wider issues surrounding allergenic response to food and more generally adverse reactions to food and food ingredients to ensure that they have followed reasonable and appropriate protocols to meet legislative requirements and also the wider social interest in food allergy and intolerance. More detailed information on allergenic foods can be found in the InformAll database (http://research.bmh.manchester.ac.uk/informAll).

Effective management of serious food allergens is an essential part of good manufacturing practice (GMP). This is an extremely complex problem to which there are no cheap or easy solutions. As outlined, there are few foods or food ingredients to which someone, somewhere, is not allergic or intolerant, in some cases in very small (microgram) quantities. Allergic reactions may range from relatively short‐lived discomfort to anaphylactic shock and death, but all should be treated seriously and safeguarded against by the manufacturer. While not detracting from the responsibility of sufferers (and their medical advisers) to identify the particular foods or food substances to which they are allergic, there is a need for due diligence by manufacturers, firstly in considering the use of known allergens as ingredients, then in warning the customer or consumer of the presence or potential presence of such allergens, and thirdly in preventing accidental cross‐contamination of products by allergens used in other products. This is not only a duty of care and a due diligence requirement, but an essential means of minimising the risk of being subject to a product liability claim. While the guidelines outlined in this chapter should prove useful in providing essential signposts towards developing organisational GMP in this area, the new development of such a policy requires commitment in the company ‘culture’, an allocation of funds and resources, and a concentrated and sustained effort by everyone led by senior management, and its application and maintenance thereafter.

8.7 Appropriate warnings to the potential purchaser are necessary, which involves labelling. The use of labelling should not be regarded as obviating the responsibilities of sufferers (and their medical advisers) to identify the particular foods or food substances to which they are allergic, or the responsibilities of manufacturers referred to in the following paragraphs.

Legislative Requirements

8.8 The Codex Alimentarius Commission Committee on Food Labelling has listed the foods and ingredients that cause the most severe reactions and most cases of food hypersensitivity. Section 4.2.1.4 of General Standards for the Labelling of Prepackaged Foods states that ‘the following foods and ingredients… shall always be declared: cereals containing gluten; i.e., wheat, rye, barley, oats, spelt or their hybridized strains and products of these; crustacea and products of these; eggs and egg products; fish and fish products; peanuts, soybeans and products of these; milk and milk products (lactose included); tree nuts and nut products; and sulphite in concentrations of 10 mg/kg or more’.⁵

In the European Union, EU Regulation (EU) No. 1169/2011 on the provision of food information to consumers has been mandatory in all Member States since 13 December 2014.⁶ It was made mandatory on 13 December 2016. Annex II list the allergens that must be declared and some exemptions, as follows:

1. cereals containing gluten, namely, wheat, rye, barley, oats, spelt, kamut or their hybridised strains, and products thereof, except:
   1. wheat‐based glucose syrups, including dextrose,⁷
   2. wheat‐based maltodextrins,
   3. glucose syrups based on barley,
   4. cereals used for making alcoholic distillates, including ethyl alcohol of agricultural origin;
2. crustaceans and products thereof;
3. eggs and products thereof;
4. fish and products thereof, except:
   1. fish gelatine used as carrier for vitamin or carotenoid preparations,
   2. fish gelatine or Isinglass used as fining agent in beer and wine;
5. peanuts and products thereof;
6. soybeans and products thereof, except:
   1. fully refined soybean oil and fat,
   2. natural mixed tocopherols (E306), natural D‐alpha tocopherol, natural alpha tocopherol acetate and natural D‐alpha tocopherol succinate from soybean sources,
   3. vegetable oils derived from phytosterols and phytosterol esters from soybean sources,
   4. plant stanol ester produced from vegetable oil sterols from soybean sources;
7. milk and products thereof (including lactose), except:
   1. whey used for making alcoholic distillates, including ethyl alcohol of agricultural origin,
   2. lactitol;
8. nuts, namely, almonds (Amygdalus communis L.), hazelnuts (Corylus avellana), walnuts (Juglans regia), cashews (Anacardium occidentale), pecan nuts (Carya illinoinensis (Wangenh.) K. Koch), Brazil nuts (Bertholletia excelsa), pistachio nuts (Pistacia vera), macadamia or Queensland nuts (Macadamia ternifolia) and products thereof, except for nuts used for making alcoholic distillates, including ethyl alcohol of agricultural origin;
9. celery and products thereof;
10. mustard and products thereof;
11. sesame seeds and products thereof;
12. sulphur dioxide and sulphites at concentrations of more than 10 mg/kg or 10 mg/L in terms of the total SO₂, which are to be calculated for products as proposed ready for consumption or as reconstituted according to the instructions of the manufacturers;
13. lupin and products thereof; and
14. molluscs and products thereof.

Commission Delegated Regulation (EU) No. 78/2014 amends Annex II of the EU Food information to Consumers listing the 14 allergens. This list is subject to future amendment. It does not preclude the manufacturer from drawing attention on the label to other food allergens. Article 21 of EU 1169/2011 on labelling of certain substances or products causing allergies or intolerances, states that:

1. Without prejudice to the rules adopted under Article 44(2), the particulars referred to in point (c) of Article 9(1) shall meet the following requirements:
   1. they shall be indicated in the list of ingredients in accordance with the rules laid down in Article 18(1), with a clear reference to the name of the substance or product as listed in Annex II; and
   2. the name of the substance or product as listed in Annex II shall be emphasised through a typeset that clearly distinguishes it from the rest of the list of ingredients, for example by means of the font, style or background colour. In the absence of a list of ingredients, the indication of the particulars referred to in point (c) of Article 9(1) shall comprise the word ‘contains’ followed by the name of the substance or product as listed in Annex II. Where several ingredients or processing aids of a food originate from a single substance or product listed in Annex II, the labelling shall make it clear for each ingredient or processing aid concerned. The indication of the particulars referred to in point (c) of Article 9(1) shall not be required in cases where the name of the food clearly refers to the substance or product concerned.
2. In order to ensure better information for consumers and to take account of the most recent scientific progress and technical knowledge, the Commission shall systematically re‐examine and, where necessary, update the list in Annex II by means of delegated acts, in accordance with Article 51.

8.9 In April 2015, the UK’s FSA issued the Food allergen labelling and information requirements under the EU Food Information for Consumers Regulation No. 1169/2011: Technical Guidance that cover the interpretation and application of allergen provisions for prepacked foods, prepacked foods for direct sale and non‐prepacked foods as outlined in the EU Food Information for Consumers Regulation (No. 1169/2011).⁸ This guide provides guidance to food businesses on allergen labelling.

8.10 In the United States of America (USA), regulation is by the Food Allergen Labelling and Consumer Protection Act of 2004 (FALCPA). From January 1 2006, all packaged foods regulated under the Act must comply with its food allergen labelling requirements if they include milk, egg, fish, crustacean shellfish, tree nuts, wheat, peanuts, soybeans (or protein derived from any of them). The US Food and Drug Administration (FDA) has produced an online Guidance for Industry: Questions and Answers Regarding Food Allergens, including the Food Allergen Labeling and Consumer Protection Act of 2004⁹ .

8.11 Exotic and novel foods are also liable to allergen labelling, e.g. products containing insects and/or their derived protein where this is known to cause an allergic reaction in individuals who are susceptible.

8.12 Existing or proposed new product formulations should be carefully examined at the product development stage to see whether there is a possibility of excluding food allergens. It is important to keep up to date with information from consumer organisations and clinicians to be aware of new food allergies and those increasing in prevalence within the population. Of course, in many cases a food allergen is essential to characterise the food, and in such cases label warning must suffice. In some cases, however, where food allergens are present as non‐characterising or minor ingredients, it may be possible to effect a substitution.

8.13 Exporters should be aware that legislative requirements for allergen labelling differ from country to country and that pre‐packed products must comply with the designated labelling in the country in which the food is sold.

8.14 Inclusion of the name of a food allergen in an ingredients list should not be regarded as adequate warning and current legislative requirements for highlighting allergens must be followed. There are minimum font size requirements for allergen such labelling.¹⁰

8.15 Where a product nominally free from food allergen is produced on a production line shared with a food allergen‐containing product, a suitable warning might be, for example, ‘May contain traces of PEANUT’. However, the use of ‘may contain’ should not be used as a way of avoiding the measures set out in Sections 8.18–8.25.

8.16 Where a product nominally free from food allergens is produced in the same factory building as a food allergen‐containing product, a suitable warning might be, for example, ‘Produced in a factory where PEANUT is also handled’. Again, this should not be used as a way of avoiding the measures set out in 8.18–8.25.

8.17 Some products may be specifically identified as ‘allergen‐free’ products, such as ‘gluten free’. EC Regulation No. 828/2014 on the requirements for the provision of information to consumers on the absence or reduced presence of gluten in food outlines the requirements for the provision of information to consumers on the absence or reduced presence of gluten in food The Regulation states ‘the statement “gluten‐free” may only be made where the food as sold to the final consumer contains no more than 20 mg/kg of gluten’. The claim of ‘very low gluten’ can only be made where the food contains no more than 100 kg/mg of gluten in the food as sold to the final consumer. and which contain cereal ingredients that have been specially processed to reduce the level of gluten.¹¹

Cross‐contact

8.18 The FDA Approaches to Establish Thresholds for Major Food Allergens and for Gluten in Food,¹² produced in 2006, describes cross‐contact as occurring when ‘as part of the food production process where residues of an allergenic food are present in the manufacturing environment and are unintentionally incorporated into a food that is not intended to contain the food allergen, and thus, the allergen is not declared as an ingredient on the food’s label’. The accidental presence of a food allergen in a product may arise in three main ways: accidental misformulation, poor labelling/packaging control leading to the product containing an allergen being packed or labelled incorrectly, or cross‐contamination by a food allergen from a different product. Misformulation resulting in the inclusion of a food allergen (or any other ingredient) not in the product formulation should be prevented by proper attention to the provisions of Chapter 10 to ensure that the products as prepared contain only the ingredients specified. Labelling control procedures are addressed in Chapter 37.

8.19 Cross‐contamination of a product by a food allergen via cross‐contact from a different product may arise as a result of a variety of activities but could be due to residues in shared equipment, airborne dust or the improper incorporation of rework material without consideration of the allergen problem. The particulate nature of the allergen should also be considered in any allergen risk assessment as this will affect the potential for contamination and the area over which contamination could occur, i.e. is the allergen, or allergen‐carrying food, a liquid, powder, solid layer or granule? It should also be considered whether the allergen is of a homogenous distribution through the food or heterogeneous as this will affect the accuracy and repeatability of sampling and monitoring activities. The allergen risk assessment must integrate with the HACCP plan and the FSMS in its entirety. This will lead to the adoption of appropriate control measures for the manufacturing situation, including a specific allergen control operational pre‐requisite programme (PRP).

8.20 In companies producing on more than one site, or in different buildings on the same site, serious consideration should be given to production segregation in separate buildings. Where separate buildings are not available, separate production equipment or timing separation is recommended. Where production equipment is shared between one or more food allergen‐free products and a food allergen‐containing product and this is unavoidable, the food allergen‐containing product should be run as the last production of the day, immediately before cleaning (e.g. on a shared production line for mixed breakfast cereals, one of which contains nuts, the product containing nuts should be run last). However, it should be recognised that cleaning afterwards, especially in a plant producing dry products, will not necessarily guarantee against small quantities of trapped material waiting to be ‘carried over’ into the first product to go through, and segregation may be the only acceptable solution. The same applies to small quantities of food allergen in airborne dust. In some instances, air‐handling systems might need to be considered.

8.21 As an example of the measures outlined in 8.20, a formal documented allergen risk assessment should be implemented on sites where peanuts or nuts, or any other allergen in fact, are processed or stored to ensure that products containing them do not contaminate peanut‐free or nut‐free product. Nuts should be stored in a designated area and processed on designated lines. Production and cleaning scheduling (time separation) should be considered between nut‐free and nut products if they are processed on the same line. The required cleaning procedures, undertaken after processing nut products to minimise risk of cross‐contact, should be validated and implemented. On an ongoing basis clean‐down procedures should be verified for efficacy, for example by means of swab tests. A potential source of contamination could be a spillage of nut products onto the packaging of nut‐free products. This contaminated packaging might then cause contamination of nut‐free products. If a spillage of nuts occurs, this must be cleared up with care, including the use of designated cleaning equipment and disposable wear, or other suitable means, for personnel to ensure that their protective clothing is not contaminated, which would then present a risk to other products. Personnel must ensure that all areas surrounding the spillage are checked for nut debris. All nut debris must be taken immediately to the appropriate disposal area. Any affected goods should be quarantined and disposed of. While nuts have been used in this example, the allergen control procedure should address all likely allergens or allergenic material that could be present in the food manufacturing premises.

The allergen control procedures of suppliers should also be considered so that the likelihood of contamination of raw materials, ingredients or packaging is minimised. Allergenic materials may also arise from processing aids, maintenance and repair activities and factory product trials, and controls should be in place to address all these potential sources. The allergen control risk assessment must also consider the likelihood of contamination and therefore the risk of staff, visitors or contractors bringing allergen‐containing food on‐site for their own consumption and/or the potential impact of catering functions on‐site. Measures should also be put in place to alert staff and site visitors to the presence of allergens on site and to prevent unnecessary exposure to those at risk.

8.22 The incorporation of rework material in a product is covered in Chapter 29, and its provisions should be operated in order to exclude from any food product not containing certain allergens, rework material that contains any of those allergens.

8.23 Formal allergen control training procedures should be in place to train all personnel so they adopt the necessary measures and understand the reasons for why they need to do so.

Quantifying Allergens in Foods

8.24 The Institute of Food Science and Technology (IFST) Information Statement on Food Allergy highlights that in order to develop the most cost‐effective food allergen management systems it is important to quantify the amount of a food allergen needed to trigger an adverse reaction in the body, which allergen(s) in the food must be monitored and how the allergen behaves during processing.¹³

8.25 In New Zealand and Australia, the membership‐based Allergen Bureau was established in 2005. The Allergen Bureau’s Voluntary Incidental Trace Allergen Labelling (VITAL) Programme¹⁴ is a standardised allergen risk assessment tool that can assist an organisation to produce an allergen assessment based on a given manufacturing situation and produce a labelling outcome that not only addresses intentional inclusion, but also the potential for cross‐contact in a resultant precautionary statement: ‘May be present: XXX’.¹⁵ Analytical methods are being developed for allergen quantification but their cost currently prohibits their use as a monitoring procedure, although they form a useful verification tool. These methods include polymerase chain reaction (PCR) assays, enzyme‐linked immuno‐sorbent assays (ELISA) and mass spectrometry.

As there are no economic analytical techniques to positively release food on a batch‐by‐batch basis, preventive measures are critical to address allergen control from the product development stage through to product labelling on consumer purchase. These measures need to be reviewed in the instance of non‐conformance being identified so that they continue to be effective.