Assessing the safety of genotoxic and carcinogenic impurities: the Margin of Exposure approach
Risk assessors at the European Food Safety Authority (EFSA) use the Margin of Exposure (MOE) approach to consider possible safety concerns arising from the presence in food and feed of substances which are both genotoxic (that is, which may damage DNA, the genetic material of cells) and carcinogenic. The presence of substances which are both genotoxic and carcinogenic in food and feed, while not desirable, could result from environmental pollution or manufacturing processes. The MOE is a ratio of two factors which assesses for a given population: the dose at which a small but measurable adverse effect is first observed and the level of exposure to the substance considered. The MOE is not used to assess the safety of regulated substances deliberately added to the food chain (for instance food and feed additives or food contact materials). However, EFSA’s Scientific Committee advises that it could be useful in assessing the safety of any genotoxic and carcinogenic impurities present in such substances at very low levels. Use of the MOE can in this way help support risk managers in defining possible actions required to keep exposure to such substances as low as possible.
Due to improving testing methods, more impurities can be detected at low levels in food and feed additives or food contact materials. Examples of these impurities include both unavoidable contaminants such as environmental pollutants, as well as residuals and by-products resulting from a production process. As some of these impurities may be both genotoxic and carcinogenic, risk assessors are required to consider their possible impact on human and animal health.
The MOE is a tool used by risk assessors to characterise the risk from exposure to genotoxic and carcinogenic substances, which may be found in food or feed. As such, the MOE approach provides an indication of the level of safety concern about a substance’s presence in food but it does not quantify the risk as such. Specifically, when using this approach, risk assessors indicate whether the MOE is of high concern, low concern, or unlikely to be of safety concern. Moreover, MOEs should be looked at on a case-by-case basis while taking account of both the level of safety concern and any uncertainties involved in deriving the MOE.
In its 2005 opinion, EFSA’s Scientific Committee expressed the view that in general a margin of exposure of 10,000 or higher, if it is based on the ‘Benchmark-dose lower bound’ (BMDL) from an animal study, would be of low concern from a public health point of view. The BMDL is a reference value derived from the Benchmark dose (BMD) which extends the use of dose-response data from studies in experimental animals or from observational epidemiological studies to better characterise and quantify potential risks.