Risk-based justification for a 10µg/kg Default Residue Limit to establish withdrawal periods for veterinary medicinal products lacking Maximum Residue Limits

Abstract

The ultimate objective of risk assessment is to establish a safe level of intake of residues of Pharmacologically Active Substances (PAS) present in foods of animal origin. Under a gold-standard assessment scenario, toxicological reference values used to establish Maximum Residue Limits (MRLs) and withdrawal periods are derived from complete toxicological data packages for the substance. However, situations may arise in which the available dataset for toxicological evaluation and subsequent determination of MRLs for PAS used in veterinary medicinal products (VMPs) is incomplete, thereby limiting the regulatory establishment of withdrawal periods. To address this limitation, the Brazilian Ministry of Agriculture and Livestock (MAPA) established, through Article 2 of Ordinance N° 200 of January 22, 2021, the possibility of applying a Default Limit of 10 ppb (10 µg/kg) as a cut-off value in residue depletion curves in edible tissues and animal-derived products for the determination of withdrawal periods. This article demonstrates that the adopted value of 10 ppb is not arbitrary but is scientifically supported by the Threshold of Toxicological Concern (TTC) concept, originally proposed by Cramer for the toxicological classification of chemical substances and incorporated into international risk assessment approaches, with references to the Codex Alimentarius and related regulatory frameworks. Dietary exposure estimations further demonstrate that a residual level of 10 ppb is scientifically justifiable and methodologically appropriate to ensure consumer safety regarding foods of animal origin, representing a conservative approach consistent with internationally accepted risk management principles.