Authors R. Kroes, D. Muller, J. Lambe, M.R.H. Lowik, J. van Klaveren, J. Kleiner, R. Massey, S. Mayer, I. Urieta, P. Verger, A. Visconti
Abstract
Exposure assessment is one of the key parts of the risk assessment process. Only intake of toxicologically significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of chemicals in foods this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets, including its fate during the processes within the food production chain; (ii) how to determine the consumption patterns of the individual foods containing the relevant chemicals; (iii) how to integrate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. The techniques used for the evaluation of these three aspects have been critically reviewed in this paper to determine those areas where the current approaches provide a solid basis for assessments and those areas where improvements are needed or desirable. For those latter areas, options for improvements are being suggested, including, for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food chemicals, harmonisation of food consumption survey methods with the option of a regular pan-European survey, evaluation of probabilistic models and the development of models to assess exposure to food allergens. In all three areas, the limitations of the approaches currently used lead to uncertainties which can either cause an over- or underestimation of real intakes and thus risks.
Given these imprecisions, risk assessors tend to build in additional uncertainty factors to avoid health-relevant underestimates. This is partly done by using screening methods designed to look for ''worst case'' situations. Such worse case assumptions lead to intake estimates that are higher than reality. These screening methods are used to screen all those chemicals with a safe intake distribution. For chemicals with a potential risk, more information is needed to allow more refined screening or even the most accurate estimation. More information and more refined methods however, require more resources. The ultimate aims are: (1) to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general; (2) to assess the consumption patterns for the foods containing these substances, including especially those parts of the population with high consumption and thus potentially high intakes; and (3) to develop and apply tools to predict reliably the likelihood of high end consumption with the presence of high levels of the relevant substances.
It has thus been demonstrated that a tiered approach at all three steps can be helpful to optimise the use of the available resources: if relatively crude tools - designed to provide a ''worst case'' estimate - do not suggest a toxicologically significant exposure (or a relevant deficit of a particular nutrient) it may not be necessary to use more sophisticated tools. These will be needed if initially high intakes are indicated for at least parts of the population. Existing pragmatic approaches are a first crude step to model food chemical intake. It is recommended to extend, refine and validate this approach in the near future. This has to result in a cost-effective exposure assessment system to be used for existing and potential categories of chemicals. This system of knowledge (with information on sensitivities, accuracy, etc.) will guide future data collection.
Research needs:
Priority research needs for food composition
Pan-European Food Composition Data Base: it is desirable to develop a standardised pan-European database for chemicals in foods including not only nutrients but also low molecular weight chemicals such as additives, contaminants/residues, and relevant non-nutrient plant components. Such a database should include information on sampling and analytical methods used. The database should preferably contain individual data points or at least information on ranges of levels found (mean/standard deviation) and the number of analyses from which this mean is derived. Key is the harmonization of methods, whereas integration of results across Europe should be approached with care considering the significant differences in actual food composition.
Processing: understanding the processes applied between farm and fork, i.e. throughout the production chain down to the consumer's kitchen, and their effect on the levels and qualities of food chemicals including substances originally present, added, or formed during processing. Such a project should also provide background on how this information has been obtained to position its usability in the process of exposure assessment. In the context of a harmonised data base, information should also be collected (and included as feasible) on natural variability of foods, i.e. due to differences between cultivars, effects of ripeness, geographical origin, including geological factors affecting for example heavy metal content, harvest and storage conditions, The latter aspects will also be relevant for the information on process effects. To be able to evaluate changes over time, the selection of appropriate analytical methods should be regularly re-evaluated for their technical appropriateness as well as for changes in production methods in agriculture and food industry, in consumer preference, and for example, regulatory and economical factors, and it should be determined how to maintain information on historical compositional data. Some work in this context is currently underway in the context of the EU EPIC programme. The optimisation of analytical methods and of sampling procedures is not normally under the control of experts involved in exposure/risk assessment, but needs to be consciously monitored to ensure applicability of data over time. Priority research needs for food consumption:
Harmonisation of food consumption survey methods: this includes the need to precisely determine exposure to priority compounds, including the determination of reasonable extremes and to understand the degree of possible underreporting and options for correction. It should ideally involve considerations to include foods on a brand name basis, i.e. via the use of bar codes, and attempt to account for the consumption of ready-to-eat dishes and away-from-home consumption, which make up an increasing part of European diets.
Evaluation of occasional peak consumption vs. mean long-term consumption: this will also help to consider possible effects of acutely toxic substances in food
Population variability: More information is needed on the variability of populations to allow better focus on the susceptibilities of individuals and specific subgroups. This applies also to genetic variability. Research in molecular genetics and nutrient-gene/gene-nutrient interactions will provide this insight and will also lead to the development of biomarkers of exposure and effects.
New food types: the development of novel and functional foods creates a need to assess exposure for possible health effects.
Pan-European Food Consumption Survey: it is desirable to organise a broad survey using such harmonised methods and parameters to ensure the availability of sufficient and comparable data also for risk assessments. When preparing such new research, it should also be considered how pre-market simulations, and post-launch data collection can be optimally used, considering the cost and resource implications, and how information available from manufacturers can be optimally integrated in intake assessments. In general, food consumption surveys need to be linkable to the proposed food composition data base for optimal evaluation, regarding the inclusion of minor food constituents beyond the macro- and micronutrients most commonly evaluated, and a common categorisation of foodstuffs. The results of such surveys should be validated for example, by duplicate diet studies using unified and standardised protocols. Integrating food consumption and chemical concentration for the purpose of modelling exposure to food chemicals.
Evaluation of probabilistic models, including validation of the software programme, comparing results of different modelling approaches using the same data sets and comparison of model outputs with actual exposure measurements, based on but probably going beyond the EU MonteCarlo project.
Development of aggregate (multi-route/multi-pathway) exposure and cumulative exposure (exposure to multiple chemicals with the same mode of action/accumulation of one chemical over time) assessment methodology.
Development of models for exposure to allergens and methods to predict the probability of adverse effects arising from such exposures (i.e. including variables such as individual susceptibility in probabilistic modelling).
Development of more validated screening tools at low costs with more realistic assumptions
For optimal use in the context of the risk characterisation process, appropriate methods are needed to link exposure models which evaluate the amount of a chemical entering the digestive tract with toxicokinetic models to estimate internal exposure.
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