Scientific Opinion on Exploring options for providing advice about possible human health risks based on the concept of Threshold of Toxicological Concern (TTC)

<p>Synthetic and naturally occurring substances present in food and feed, together with their possible breakdown or reaction products, represent a large number of substances, many of which require risk assessment. EFSA’s Scientific Committee was requested to evaluate the threshold of toxicological concern (TTC) approach as a tool for providing scientific advice about possible human health risks from low level exposures, its applicability to EFSA’s work, and to advise on any additional data that might be needed to strengthen the underlying basis of the TTC approach. The Scientific Committee examined the published literature on the TTC approach, undertook its own analyses and commissioned an <em>in silico </em>investigation of the databases underpinning the TTC approach. The Scientific Committee concluded that the TTC approach can be recommended as a useful screening tool either for priority setting or for deciding whether exposure to a substance is so low that the probability of adverse health effects is low and that no further data are necessary. The following human exposure threshold values are sufficiently conservative to be used in EFSA’s work; 0.15 μg/person per day for substances with a structural alert for genotoxicity, 18 μg/person per day for organophosphate and carbamate substances with anti-cholinesterase activity, 90 μg/person per day for Cramer Class III and Cramer Class II substances, and 1800 μg/person per day for Cramer Class I substances, but for application to all groups in the population, these values should be expressed in terms of body weight, i.e. 0.0025, 0.3, 1.5 and 30 μg/kg body weight per day, respectively. Use of the TTC approach for infants under the age of 6 months, with immature metabolic and excretory systems, should be considered on a case-by-case basis. The Committee defined a number of exclusion categories of substances for which the TTC approach would not be used.</p&gt

International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures”) is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area