The use of veterinary medicinal products can result in the presence of ‘non-allowed’ pharmacologically active substances in food of animal origin. Reference points for action (RPAs) are used to ensure the functioning of controls for such food and to determine compliance with Community legislation. RPAs are currently based on analytical considerations (i.e. the lowest concentration that can be quantified using a validated analytical method), but a new EFSA report gives guidance on an approach which additionally considers toxic potential. The aim is “to define an analytical concentration for a non-allowed pharmacologically active substance that can be determined by official control laboratories and is low enough to adequately protect the consumers of food commodities that contain that substance”.

The approach is based on the derivation of a toxicologically based limit of quantification (TBLOQ), defined as “the concentration in food which is likely not to be of toxicological concern for the consumer”. If this value is greater than the analytically-based reasonably achievable lowest limit of quantification (RALLOQ), the RALLOQ is adequate for use as the RPA. If the TBLOQ is lower than the RALLOQ, the analytical sensitivity should be improved to sufficiently reduce the RALLOQ. If this is not possible, a substance-specific risk assessment should be conducted.

The basis for the TBLOQ is a set of toxicological screening values (TSVs) derived by EFSA for three groups of ‘non-allowed’ substances:

  • Group I substances are those for which a genotoxic mode of action cannot be excluded. A TSV of 0.0025 μg/kg bw/day was recommended, this being the existing threshold of toxicological concern (TTC) value for substances with suspected genotoxicity.
  • Group II substances include corticoids and agents acting on the nervous and reproductive systems. A TSV of 0.0042 μg/kg bw/day was recommended, the lowest acceptable daily intake (ADI) seen for 20 similar, but ‘allowed’, substances evaluated by the European Medicines Agency (EMA).
  • Group III contains the remaining substances. A TSV of 0.65 μg/kg bw/day was recommended, the overall 5th percentile of the ADIs for similar, but ‘allowed’, substances evaluated by EMA.

It was noted that the TSVs listed should not apply for high-potency carcinogens (i.e. aflatoxin-like, azoxy- or N-nitroso-compounds, benzidines and hydrazines), for substances causing “blood dyscrasias” (such as aplastic anaemia), or for those causing allergy. These will require substance-specific risk assessment.

European Food Safety Authority. Panel on Contaminants in the Food Chain (CONTAM). Guidance on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin. EFSA Journal 2013, 11(4): 3195.


The above item was taken from the May 2013 issue of Toxicology and Regulatory News which is sent automatically to members of bibra (click here for more details).

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