Scientific Opinion on the safety and efficacy of Koffogran (nicarbazin) as a feed additive for chickens for fattening

Koffogran (containing 25 % nicarbazin) is intended to be used as a coccidiostat for chickens for fattening up to an age of 28 days. Feeding 125 mg nicarbazin/kg feed was safe for chickens for fattening (margin of safety about 1.5) and effective in controlling coccidiosis. Ingested nicarbazin is rapidly split into its components 2-hydroxy-4,6-dimethylpyrimidine (HDP) and 4,4’-dinitrocarbanilide (DNC). DNC is the marker residue, liver the target tissue. HDP-related residues are much lower than those derived from DNC. Nicarbazin is not genotoxic. In sub-chronic rat studies, no NOAEL could be derived for nicarbazin, but a NOAEL of 709 mg/kg bw/day was identified for DNC. Those differences may be related to the higher systemic exposure of rats to DNC when administered as nicarbazin instead of DNC alone. No major concern appeared in multigeneration reproduction studies in rats at 300 mg DNC + 100 mg HDP/kg bw/day and in developmental studies with rats and rabbits at 70 and 60 mg nicarbazin/kg bw, respectively. As the consumer is exposed to DNC rather than nicarbazin, an ADI was set for DNC with 0.77 mg/kg bw/day, derived from the NOAEL for elevated serum ALT in a two-year dog study (154 mg DNC/kg bw/day) applying a safety factor of 200. MRLs of 15, 6, 4 and 4 mg DNC/kg liver, kidney, muscle and skin/fat, respectively, were proposed. Applying those MRLs consumer exposure would not exceed 24 % of the ADI. A one-day withdrawal period was considered as adequate. Nicarbazin was not an irritant or sensitiser to skin, but a slight irritant to eyes. Inhalatory exposure of users to nicarbazin was negligibly small. No safety concern for the soil compartment, groundwater or by secondary poisoning was identified, the risk for surface water could however not be assessed.