Quantifiable risk-benefit assessment of micronutrients: From theory to practice.

The EU Food Supplements Directive (2002/46/EC) mandates the determination of both maximum and minimum permitted levels (MPLs) for micronutrients. In order to determine MPLs which are feasible for particular population groups, a scientific approach should be used in which risk of high intake, risk of inadequacy and benefits are assessed in an integrated way taking all available data and severity and incidence of effect into account. In 2004, Renwick et al.

Relevance of bioaccumulating substances in the TTC concept.

Recently, the European Food Safety Authority (EFSA) stated that the Threshold of Toxicological Concern (TTC) thresholds should not be used for substances that are known or predicted to accumulate. Bioaccumulation of substances is usually considered unfavourable but so far a relation with toxicity at low dose exposure is insufficiently investigated to draw conclusions on the relevance of bioaccumulation at low dose exposure. In this manuscript it is investigated which physical chemical properties are related to bioaccumulation in order to predict accumulating properties of a substance, and is evaluated if the toxicity of known bioaccumulating substances is higher than for non-accumulating substances.

A TTC threshold for acute oral exposure to non-genotoxic substances.

To derive an acute TTC threshold, the correlation between Allowable Daily Intakes (ADIs, chronic values) and Acute Reference Doses (ARfDs) of pesticides evaluated in the EU was investigated and their distributions were compared. The correlation between ARfDs and ADIs was significant (p = 0.01), but weak (r(2) = 0.

Reevaluation of the Munro dataset to derive more specific TTC thresholds.

The threshold of toxicological concern (TTC) concept is a risk assessment tool for substances present at low oral exposure and lacking hazard data. In the past, several thresholds were elaborated by Munro et al. (1996) and Kroes et al.

Complex mixtures: relevance of combined exposure to substances at low dose levels.

Upon analysis of chemically complex food matrices a forest of peaks is likely to be found. Identification of these peaks and concurrent determination of the toxicological relevance upon exposure is very time consuming, expensive and often requires animal studies. Recently, a safety assessment framework based on the Threshold of Toxicological Concern (TTC) was published to assess the safety of chemically complex matrices more efficiently.