Preliminary evaluation of the safety and efficacy of paromomycin sulphate for turkeys for fattening and turkeys reared for breeding' Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed

Following a request from the European Commission (Article 15 of Regulation (EC) No 1831/2003), the European Food Safety Authority (EFSA) was asked to deliver a preliminary evaluation of the safety and efficacy of paromomycin sulphate when used as feed additive under the category coccidiostats/histomonostats. HistoBloc (R) 9 contains 8 % paromomycin sulphate, an aminoglycoside antibiotic, produced by fermentation of Streptomyces chrestomyceticus. It is applied to prevent histomoniasis in turkeys for fattening and turkeys reared for breeding at concentrations between 100 and 400 mg kg(-1) complete feed. The safety for the target animal of paromomycin sulphate from histoBloc (R) at the highest proposed dose (400 mg kg(-1) diet) could not be established due to the absence of data. Paromomycin sulphate shows an antimicrobial effect on susceptible bacterial strains at levels considerably lower than those proposed for feed use. Even at the lowest proposed feed concentration (100 mg kg(-1) diet), it selects for resistance and cross-resistances at high frequency against a variety of other aminoglycosides among intestinal bacteria. As aminoglycoside antibiotics are used in human and veterinary medicine, serious consequences for antibiotic therapy in humans and animals can be anticipated following the use of paramomycine as a feed additive. Data on paromomycin sulphate from histoBloc concerning metabolism and toxicology were not supplied. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) follows therefore in these aspects the Summary Report of EMEA/CVMP on paromomycin sulphate. The limited data available on paromomycin sulphate metabolism indicate that (i) orally administered paromomycin sulphate is absorbed to a very limited extent, (ii) negligible biotransformation occurs following absorption, (iii) no accumulation in tissues occurs (with the exception of the kidney) and (iv) paromomycin sulphate constitutes most of the residues in tissues. Paromomycin sulphate is the marker residue. No conclusions on the similarity of the metabolic fate of paromomycin sulphate in turkeys and laboratory animals can be drawn. Paromomycin sulphate has a very low oral acute toxicity, it is not mutagenic, genotoxic, carcinogenic or teratogenic. Oral chronic toxicity in dogs resulted in the lowest NOEL of approximately 3.4 mg paromomycin sulphate kg-1 bw, leading to a toxicological ADI of 0.034 mg kg-1 bw. A residue study with histoBloc r in turkeys, at the highest dose proposed for use (400 mg kg(-1) feed), indicates higher concentrations of paromomycin sulphate in kidney, followed by muscle and liver. No measurement was performed in skin/fat. The FEEDAP Panel estimates consumer exposure after a ten-day withdrawal, extrapolating skin/fat data from a study in chickens, to 0.214 mg day-i, representing about 10 % of the toxicological ADI. As MRLs, the FEEDAP Panel retains the EMEA/CVMP values for liver, kidney and muscle (1.5, 1.5 and 0.5 mg kg(-1), respectively) and adds the provisional value of 1.5 mg kg(-1) for skin/fat. The corresponding consumer exposure would represent 28 % of the toxicological ADI. A withdrawal time of ten days is proposed for turkeys for fattening. According to the applicant, histoBloc r is harmful by inhalation and if swallowed. It is also irritating to the eyes. Other issues, such as the potential for sensitisation, have not been considered. Preliminary calculations indicate that the trigger values for soil and groundwater would be exceeded and thus a Phase II assessment is needed. In the absence of any experimental data on the fate and ecotoxicity of paromomycin sulphate, the FEEDAP Panel cannot conclude on the safety of histoBloc (R) for the environment. Due to the complete lack of data under practical conditions and despite the probable efficacy of paromomycin sulphate against histomoniasis in turkeys, a conclusion on the efficacy of histoBloc (R) 9 under field conditions, particularly on the effective dose, is not possible. Recommendations have been made concerning the protection of the user and post-market monitoring.