Update of the Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on a request from the European Commission related to the safety and efficacy of “Kokcisan 120G”

The European Food Safety Authority received a request from the European Commission to issue an opinion on the safety of Kokcisan 120G for chickens for fattening based on the new data provided by the applicant in the supplementary dossier. Data submitted by the applicant on Kokcisan 120G were previously reviewed by the FEEDAP Panel in May 2004 and found to be insufficient for conclusions to be reached on efficacy and safety. In response to this review the applicant has conducted further studies to address the inadequacies previously identified and the additional studies are reviewed in the following opinion. From the supplementary metabolic studies, it has been concluded that unchanged salinomycin represents less than 10% of the total radioactivity in the excreta regardless of gender. The results presented identify more than 20 metabolites in chicken excreta, each representing less than 10% of the total radioactivity. The metabolic profiles in chicken and rat excreta and tissues are found to be qualitatively similar. Kinetics study of total residues and SAL-Na residues in chicken tissues from animals dosed at maximum dose proposed was provided and Salinomycin sodium could be considered as a marker residue. Based on the revised study report provided by the applicant of a 13-week study in dogs previously considered, the NOEL derived from the study in question has been reviewed and changed to 0.5 mg SAL Na kg-1 bw day-1. A reproduction and teratology study in rabbits provided a NOEL for maternal toxicity of 0.5 mg SAL-Na kg-1 bw day-1. Pharmacology studies by the oral route in dogs indicated a NOEL for pharmacological effects (heart rate increase) of 0.625 mg kg-1 bw. A chronic toxicity study in rats was reviewed and concluded overall to be poorly conducted, yielding insufficient numbers of animals for scheduled necropsy to comply with current standards and regulatory guidelines. The study is compromised by high mortality, which may have served to select the least sensitive animals for the latter stages of the study. The changes to dose and route of administration leave some uncertainty as to the exact dose which each treatment group received, although this problem alone would not have been insurmountable. The number of animals which died during this study caused concerns for animal welfare. Bringing all of the above factors together, it is not possible for the FEEDAP Panel to reach any conclusion on the chronic safety of Kokcisan 120G in rats from the study provided. Since no adequate chronic study is available for this product it is not possible for the FEEDAP Panel to derive an ADI or MRL from the submitted data. Setting an MRL is further impeded by the lack of consistent data for the marker residue in the relevant tissues and the lack of data for the proposed target tissue skin/fat. It cannot be excluded that the use of Kokcisan 120G at the recommended dose range poses a risk for the terrestrial compartment. In the previous opinion on this product, the FEEDAP Panel criticized the lack of an up-to-date floor pen studies. The applicant submitted a new study in August 2005 and The FEEDAP Panel has assessed this study and included the results in Appendix, as this issue is not specifically addressed in the question from the European Commission. This study has shown that Kokcisan 120G at a level of 60 mg salinomycin sodium kg-1 diet is effective in supporting the growth of chicken for fattening under the conditions of an artificial Eimeria infection