THE GENERAL FRAMEWORK OF RISK ASSESSMENT

Food contains a wide range of substances which are either desired (nutrients, additives) or undesired, such as mycotoxins. As a result, both nutritional and food safety issues are important determinants of public health and therefore deserve continued attention from scientific and from policy perspective. A very important aspect within mycotoxin research is risk assessment. According to the International Programme on Chemical Safety (IPCS, 2004) health risk is defined as the probability of an adverse effect in an organism, system or population caused under specified circumstances by exposure to an agent. The use of a structured risk analysis process facilitates decision-making in the area of food safety. Risk analysis has been defined by the Codex Alimentarius Commission as a process consisting of three components: risk assessment, risk management and risk communication. Within risk analysis, the functional separation between risk assessors and risk managers is essential to ensure scientific objectivity of the risk assessment process (FAO/WHO, 2008).

Risk assessment of food chemicals can be generally described as characterising the potential

hazards and the associated risks to life and health resulting from exposure of humans to chemicals present in food over a specified period. It provides a mechanism for the structured review of information relevant to estimating health outcomes in relation to exposure to chemicals present in food and forms the scientific basis for the risk management executed by governments. Risk assessment is defined as a four-step process (figure 3.1.). Within this chapter the different steps will be explained with a direct link to the scope of this doctoral thesis.

Figure 3.1. Four-step process of risk assessment

Hazard identification is the first of four steps in risk assessment. The purpose of food

chemical hazard identification is to evaluate the weight of evidence for adverse health effects, based on assessment of all available data on toxicity and mode of action. It is designed to address two questions namely the nature of the health hazard that an agent may pose and the circumstances under which the hazard may be expressed. The nature of the toxicity or adverse health effect and the affected target organs are identified using in vitro and in vivo toxicity tests. The hazard identification concerns the determination of the different compounds to be included in the analysis of the risks related to mycotoxins. Although a very wide range of mycotoxins may accumulate in the food chain, it was decided to limit this study to the most abundant mycotoxins with emphasis on those with available human biomarkers of exposure. For this reason aflatoxins, CIT, fumonisins, ochratoxins, trichothecenes and ZEN were included in this study whereby dietary intake is the main route of exposure (see chapter 1).

Hazard characterisation describes the relationship between the dose/exposure and the

incidence of the adverse health effect (dose-response relationships) and includes all toxicokinetic and toxicodynamic data concerning mycotoxins (see chapter 2). In cases where the toxic effect is assumed to have a threshold, hazard characterisation usually results in the establishment of health-based guidance values such as a tolerable weekly intake (TWI) or a tolerable daily intake (TDI). This establishment is based on the determination of a NOAEL in toxicological studies and the application of an uncertainty factor. The uncertainty factor means that the lowest NOAEL in animal studies is divided by 100, 10 for extrapolation from animals to humans and 10 for variation between individuals, to arrive at a tolerable intake

Hazard identification Hazard characterisation Exposure assessment Risk characterisation

level. In cases where the data are inadequate, higher safety factors are used (FAO, 2003). Table 3.1. gives an overview of the health-based guidance levels for mycotoxins in humans.

Table 3.1. Health-based guidance levels for mycotoxins in humans

Mycotoxin Health-based guidance level Reference

Aflatoxins No TDI since carcinogenic effects

Fumonisins Group TDI = 2 μg/kg BW/day FAO/WHO (2012) Ochratoxin A TWI = 0.12 µg/kg BW/week EFSA (2006) Deoxynivalenol + acetylated forms Group TDI = 1 μg/kg BW/day FAO/WHO (2010)

T-2 + HT-2 toxin Group TDI = 0.1 μg/kg BW/day EFSA (2011a) Zearalenone TDI = 0.25 μg/kg BW/day EFSA (2011b)

The largest part of the work executed in this PhD-thesis is related to the exposure

assessment. The latter has been defined as the qualitative and/or quantitative evaluation of

the likely intake of chemical agents via food as well as exposure from other sources if relevant (FAO/WHO 2008). In the case of food chemicals, dietary intake is usually estimated by models combining data on food consumption with concentration data measured in foods and food groups and the likelihood of consumers eating large amounts of the foods in question (high consumers) and of the chemical being present in these foods at high levels. Usually a range of intake or exposure estimates will be provided and estimates may be broken down by subgroup of the population (e.g. children, adults). Because of some uncertainties related to this approach, the direct measurement of biomarkers of exposure has become an added value in evaluating exposure. It is the only available tool that integrates exposures from all sources (Choi et al., 2015). Furthermore, the individual variation in ADME processes is integrated when using biomarkers, whereby a more accurate assessment of exposure can be performed at the individual level. The experimental part of this PhD-thesis focuses on the exposure assessment of mycotoxins for the Belgian population using biomarker analysis (see chapter 5-7).

The latter step, risk characterisation, integrates the information collected in the preceding three steps. The information from the intake or exposure assessment and the hazard characterisation is integrated into advice suitable for decision-making in risk management. Risk characterisation provides estimates of the potential risk to human health under different scenarios. It can be qualitative or quantitative. It should include a clear explanation of any uncertainties resulting from gaps in the science base and information on susceptible subpopulations. Finally the risk of mycotoxin exposure of the Belgian population was evaluated within this study. Based on the urinary mycotoxin concentrations, the dietary intake was estimated and was compared to TDI’s (see chapter 6). The results of this PhD- thesis can help policy makers to get a better picture of the mycotoxin exposure of the Belgian population and to develop a strategy to tackle the potential public health problem related to mycotoxin exposure.

Risk assessment is followed by risk management, which is the process, distinct from risk assessment, of weighing policy alternatives, in consultation with all interested parties, considering risk assessment and other factors relevant for the health protection of consumers and if needed selecting appropriate prevention and control options. Risk managers are responsible for the final decisions on establishing maximum limits for contaminants such as mycotoxins.

Additionally risk communication is defined as the interactive exchange of information and opinions throughout the risk analysis process concerning risk, risk-related factors and risk perceptions, among risk assessors, risk managers, consumers, industry, the academic community and other interested parties, including the explanation of risk assessment findings and the basis of risk management decisions (FAO/WHO 2008).