Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on a request from the Commission related to the safety and efficacy of ‘Clinacox 0.5 %’ based on diclazuril for rabbits for fattening and breeding

Clinacox contains 0.5 % diclazuril, a synthetic chemical, as the active ingredient and is intended for the control of coccidiosis, a debilitating protozoal infection, in rabbits for fattening and rabbits for breeding. The minimum and maximum concentration of diclazuril proposed by the applicant is 1 mg kg-1 complete feed. The European Food Safety Authority has been asked by the European Commission to assess the efficacy and the safety of this additive for the target animal, the user, consumer and the environment. Studies with artificial infection showed that 1 mg diclazuril kg-1 feed is the effective dose for controlling coccidiosis in the liver and intestine of rabbits. In field trials, it could be shown that 1 mg diclazuril kg-1 feed protected rabbits for fattening and breeding at least as effectively as other coccidiostats tested. However, a conclusive assessment of present day efficacy of Clinacox 0.5 % in field cannot be made due to the lack of recent data, particularly relating to resistance of rabbit-specific Eimeria. Diclazuril was tolerated at six-fold the highest dose proposed in rabbits for fattening and in does for breeding. Diclazuril did not show antibacterial or antifungal activity. The FEEDAP Panel considers 1 mg diclazuril kg-1 as safe for rabbits for fattening and breeding (with a margin of safety of at least 6). Diclazuril is absorbed and metabolised at a very low extent. Diclazuril is mainly excreted in the feces as unchanged compound. Metabolites represent each less than 10 % of total residues in tissues, with the exception of fat where one diclazuril impurity and/or metabolite represents about 35 % of total residues. The liver is the target tissue and diclazuril is the marker residue in all tissues. Diclazuril exhibits very low acute toxicity and shows no evidence of genotoxicity, carcinogenicity, embryotoxicity, fetotoxicity or teratogenicity. The overall NOEL is 2.9 mg kg-1 bw based on chronic toxicity/carcinogenicity study in mice, from which an ADI of 1.7 mg per 60 kg person per day is normally derived, applying a safety factor of 100. However, a pre-requisite for applying an ADI is the similarity of the metabolic fate of the active substance in the target animal and laboratory animal, which ensures that the laboratory animals used in the toxicological studies are exposed to the same residues as will be the consumer. Common metabolites with the rat have been identified, but the diclazuril impurity/metabolite present in rabbit tissues was not found in this species. Consequently, the FEEDAP Panel set, as a minimum requirement, demonstration of its absence of genotoxicity. This compound proved to be non-mutagenic in an in vitro test. However, the FEEDAP Panel considers that a single bacterial mutagenicity test would not allow conclusions on the absence of genotoxicity in mammalian systems. Consequently, a safety assessment of the residues in edible rabbit tissues cannot be carried out as long as reassurance on the lack of genotoxic potential of the diclazuril impurity/metabolite is not available. Therefore, no MRL and no withdrawal period for diclazuril in Clinacox 0.5 % can be proposed. Diclazuril has low irritation potential for the eye and skin and low acute inhalatory toxicity and therefore poses no risk for the user of the product. The use of Clinacox 0.5 % at the recommended dose does not pose a risk for the terrestrial or aquatic environment.