Cross-contamination of non-target feedingstuffs by maduramicin authorised for use as a feed additive Scientific opinion of the Panel on Contaminants in the Food Chain

Maduramicin ammonium is a polyether carboxylic ionophore agent that is authorised according to Commission Regulation No (EC) 1464/2004 as a coccidiostat for use in chickens for fattening and turkeys (until a maximum age of 16 weeks) with a maximum content of the active substance in feed of 5 mg/kg and a withdrawal period of five days. Despite the requirements set for feed business operators in Regulation No (EC) 183/2005, it is generally acknowledged that under practical conditions during the production of mixed feeds, a certain percentage of a feed batch remains in the production circuit and these residual amounts can contaminate the subsequent feed batches. This cross-contamination may result in the exposure of non-target animal species, and hence the potential health risks for non-target animal species as well as potential residues in foods derived from these non-target animal species have been evaluated. Species differences in the susceptibility to maduramicin and the small margin of safety between the maximum authorised level and the minimum toxic dose in non-target animal species have been shown. Signs of intoxication have been reported in rabbits, cattle and sheep at the maximum authorised level in chickens for fattening and turkeys (5 mg/kg). The toxic syndromes include cardiomyopathy associated with congestive heart failure and mild to severe skeletal muscle lesions, consistent with the mode of action of polyether ionophores. In turkeys, depression of body weight gain was seen above 10 mg/kg feed and lethal effects were observed in pigs at 37.5 mg/kg feed. The Panel on Contaminants in the Food Chain (CONTAM Panel) concluded that accidental ingestion of the maximum authorised level of maduramicin in feed for chickens for fattening and turkeys may present a health risk for several non-target animal species. Cross-contamination of feed at a level of 10% (0.5 mg/kg feed) of the maximum authorised maduramicin concentration, would result in an intake for non-target animal species of up to 0.025 mg/kg b.w. per day of maduramicin. This level is below the overall no observed effect level (NOEL) of 0.16 mg/kg b.w. as identified by the Scientific Committee on Animal Nutrition (SCAN) from a two year oral (feeding) study in rats, and below the lowest observed adverse effect level (LOAEL) of 0.075 mg/kg b.w. per day of the most sensitive species, the rabbit. The CONTAM Panel concluded that adverse health effects are unlikely to occur in non-target animals as a result of cross-contamination of feed at a level up to 10% of the maximum authorised level of maduramicin in feed for target animals. No kinetic or occurrence data were available to estimate the amount of maduramicin residues in eggs, milk or in meat and offal from non-target animal species. Hence, consumer exposure was estimated using kinetic data at zero withdrawal time from chickens for fattening that were given the maximum authorised level of 5 mg maduramicin/kg feed. These data were extrapolated to a concentration of 0.5 mg/kg feed to correspond to feed cross-contaminated with maduramicin at a level of 10% of the maximum authorised level. Consumption of such poultry products (100 g of liver, 300 g muscle, 90g skin/fat and 10g of kidney) could give an intake of 2.2 mu g maduramicin equivalents (total radioactive residues) per person corresponding to 0.037 mu g/kg b.w. for a 60 kg consumer, which represents 3.7% of the ADI of 1 mu g/kg b.w. per day as established by the SCAN. Even though kinetic and tissue deposition can differ between chickens for fattening and non-target animal species, an exceedance of the ADI is unlikely to occur. Therefore, the CONTAM Panel concluded that the very limited data provided no indication of an appreciable risk to consumers' health from the ingestion of maduramicin residues in products from animals exposed to feed cross-contaminated up to a hypothetical level of 10% of the maximum authorised level.