1056 A.Konig et al.Food and Chemical Toxicology 42 (2004)1047-1088 of the manufacturer of the food.Methods vary from and to link such variations to health outcomes (FSA, establishing channels of communication in the firm to 2002).Possible requirements for post-market monitor- receive direct consumer feedback on the product,to the ing of GM crops with more complex modifications, repurchase of products to determine the quality of the including altered nutritional value,are discussed in product on the supermarket shelf. Section 4.6. Post-market monitoring programmes may serve to confirm the absence of specific adverse health effects of certain products after they have been marketed.The 4.The safety assessment of foods derived from GM feasibility and validity of post-market monitoring crops depends on the health endpoint of interest and on the way the product is marketed.First,post-market mon- Safety considerations for foods derived from GM itoring of manifestation of adverse effects from intake of crops are fundamentally the same as those for conven- specific foods is most feasible if it is driven by an tional foods or other types of novel foods (Cockburn, hypothesis on a potential and specific adverse effect that 2002).Since the genetic improvement of crops has is acute and has distinctive symptoms.Acute adverse always been the aim of plant selection and breeding, effects generally associated with relatively high intakes 'traditional'approaches are appropriate in order to of a substance,or allergic reactions,are likely to become assess the safety of foods derived from all GM crops, apparent by post-market monitoring for spontaneous regardless of the crop species or the trait introduced by events.However,long-term or rare effects require genetic modification. generally a more targeted and intrusive study design. This section sets out a systematic stepwise approach Randomised controlled human trials could be used to on how to select appropriate combinations of test investigate possible medium/long term effects,but the methods to assess the safety of foods derived from GM wide variation in diets and dietary components from crops(Figs.I and 2).The objective of the assessment is day to day and year to year should be recognised.While to determine whether these new foods are at least as safe clinical studies in humans may provide wider assurance as foods produced from conventional crops;this of safety of whole foods.they cannot fully reproduce approach hence offers a high level of safety assurance. the diversity of the populations who will consume the The outlined approach serves to structure case-by- marketed product.The possibility therefore remains case assessments of specific products;it provides gui- that unpredicted side effects may occur in some sectors dance on how to design a test programme for the safety of the population,such as those with certain disease assessment of a GM crop that is tailored to the specific conditions or with particular genetic characteristics.In characteristics of the parent crop and the introduced addition,risk assessment relies on an estimate of expo- trait(s).The safety assessment focuses on the new gene sure to the food,which is variable and subject to product(s)and of whole foods derived from the GM uncertainty before the food is marketed.Critical issues crop.Both intended and potential unintended effects to the success of a post-market monitoring programme from the genetic modification are taken into account. relating to the marketing approach of the foods are the The assessment involves the following steps:(i)char- ability to estimate exposure with reasonable accuracy acterisation of the parent crop;(ii)characterisation of (traceability)and to match any reported effects to the the donor organism(s)from which any recombinant consumption of the material (Wal et al.,2003).For DNA sequences are derived,the transformation pro- identity-preserved products this may be feasible, cess,and the introduced recombinant DNA sequences; whereas for commodities it is much more difficult,if not (iii)safety assessment of the introduced gene products impossible. (proteins and metabolites);and (iv)food safety assess- To date,no GM crop has been placed on the market ment of whole food derived from,or edible part of,the for which post-market monitoring was deemed neces- GM crop. sary.The current safety testing strategy has been con- The assessment focuses on any changes introduced sidered sufficiently predictive for these approvals. through the genetic modification,including introduced Problems limiting the interpretation of post-market genes and gene products,and potentially altered levels monitoring of foods derived from commodity crops of endogenous compounds or the formation of new have been highlighted(FAO/WHO,2000).The United metabolites.Methods for the detection of unexpected Kingdom Food Standards Agency has commissioned a changes in the composition due to the genetic modifi- study to examine the feasibility of using supermarket cation process are discussed and evaluated in the paper and household survey data for post-market monitoring by Cellini et al.(2004).Possible consequences of trans- of novel foods.This study assesses the government's fer of the recombinant sequences to gastrointestinal ability to detect variations of food purchasing and microflora or to humans should also be assessed and are consumption at the district level in Great Britain,as evaluated in the paper by Van den Eede et al.(2004). this is seen as an indicator for the feasibility to detect The assembled information may also help to identifyof the manufacturer of the food. Methods vary from establishing channels of communication in the firm to receive direct consumer feedback on the product, to the repurchase of products to determine the quality of the product on the supermarket shelf. Post-market monitoring programmes may serve to confirm the absence of specific adverse health effects of certain products after they have been marketed. The feasibility and validity of post-market monitoring depends on the health endpoint of interest and on the way the product is marketed. First, post-market mon￾itoring of manifestation of adverse effects from intake of specific foods is most feasible if it is driven by an hypothesis on a potential and specific adverse effect that is acute and has distinctive symptoms. Acute adverse effects generally associated with relatively high intakes of a substance, or allergic reactions, are likely to become apparent by post-market monitoring for spontaneous events. However, long-term or rare effects require generally a more targeted and intrusive study design. Randomised controlled human trials could be used to investigate possible medium/long term effects, but the wide variation in diets and dietary components from day to day and year to year should be recognised. While clinical studies in humans may provide wider assurance of safety of whole foods, they cannot fully reproduce the diversity of the populations who will consume the marketed product. The possibility therefore remains that unpredicted side effects may occur in some sectors of the population, such as those with certain disease conditions or with particular genetic characteristics. In addition, risk assessment relies on an estimate of expo￾sure to the food, which is variable and subject to uncertainty before the food is marketed. Critical issues to the success of a post-market monitoring programme relating to the marketing approach of the foods are the ability to estimate exposure with reasonable accuracy (traceability) and to match any reported effects to the consumption of the material (Wal et al., 2003). For identity-preserved products this may be feasible, whereas for commodities it is much more difficult, if not impossible. To date, no GM crop has been placed on the market for which post-market monitoring was deemed neces￾sary. The current safety testing strategy has been con￾sidered sufficiently predictive for these approvals. Problems limiting the interpretation of post-market monitoring of foods derived from commodity crops have been highlighted (FAO/WHO, 2000). The United Kingdom Food Standards Agency has commissioned a study to examine the feasibility of using supermarket and household survey data for post-market monitoring of novel foods. This study assesses the government’s ability to detect variations of food purchasing and consumption at the district level in Great Britain, as this is seen as an indicator for the feasibility to detect and to link such variations to health outcomes (FSA, 2002). Possible requirements for post-market monitor￾ing of GM crops with more complex modifications, including altered nutritional value, are discussed in Section 4.6. 4. The safety assessment of foods derived from GM crops Safety considerations for foods derived from GM crops are fundamentally the same as those for conven￾tional foods or other types of novel foods (Cockburn, 2002). Since the genetic improvement of crops has always been the aim of plant selection and breeding, ‘traditional’ approaches are appropriate in order to assess the safety of foods derived from all GM crops, regardless of the crop species or the trait introduced by genetic modification. This section sets out a systematic stepwise approach on how to select appropriate combinations of test methods to assess the safety of foods derived from GM crops (Figs. 1 and 2). The objective of the assessment is to determine whether these new foods are at least as safe as foods produced from conventional crops; this approach hence offers a high level of safety assurance. The outlined approach serves to structure case-by￾case assessments of specific products; it provides gui￾dance on how to design a test programme for the safety assessment of a GM crop that is tailored to the specific characteristics of the parent crop and the introduced trait(s). The safety assessment focuses on the new gene product(s) and of whole foods derived from the GM crop. Both intended and potential unintended effects from the genetic modification are taken into account. The assessment involves the following steps: (i) char￾acterisation of the parent crop; (ii) characterisation of the donor organism(s) from which any recombinant DNA sequences are derived, the transformation pro￾cess, and the introduced recombinant DNA sequences; (iii) safety assessment of the introduced gene products (proteins and metabolites); and (iv) food safety assess￾ment of whole food derived from, or edible part of, the GM crop. The assessment focuses on any changes introduced through the genetic modification, including introduced genes and gene products, and potentially altered levels of endogenous compounds or the formation of new metabolites. Methods for the detection of unexpected changes in the composition due to the genetic modifi- cation process are discussed and evaluated in the paper by Cellini et al. (2004). Possible consequences of trans￾fer of the recombinant sequences to gastrointestinal microflora or to humans should also be assessed and are evaluated in the paper by Van den Eede et al. (2004). The assembled information may also help to identify 1056 A. Ko¨nig et al. / Food and Chemical Toxicology 42 (2004) 1047–1088