Summary
Nitarsone (4-nitrophenylarsonic acid 4-NPA) is used to control blackhead disease, a debilitating protozoal infection in turkeys. The additive is due for evaluation to comply for a provisional authorisation for a maximum period of five years. The European Commission asked the European Food Safety Authority to make a preliminary evaluation of the safety of 4- nitrophenylarsonic acid, and its metabolites when it is used as feed additive for animal nutrition. The additive is not yet in use in the European Union.
Nitarsone (a chemically synthesized organoarsenical) at a dose level of 187.5 mg of 4-NPA kg-1 of feed is recommended to be administered to turkeys from 2 weeks until 12 weeks of age. The very limited data derived from efficacy studies indicate a possible margin of safety to be four times the recommended dose (750/187.5 mg 4-NPA kg-1). However, the FEEDAP Panel expressed their concern to set a preliminary margin of safety value because the studies are more than 40 years old, the number of animals per group is low, the treated animals are all infected, the duration of the experiments are short and the effects of 4-NPA to gut flora are not explored.
No data are available concerning the metabolism of 4-NPA in turkeys. The metabolic pathways of 4-NPA in the laying hen indicate that the arsanilic acid is the major metabolite excreted with no release of inorganic arsenic. However, the methods used to investigate 4-NPA metabolism are questionable in terms of specificity and sensitivity. No data are given concerning the nature of tissue residues. No data have been supplied on the metabolism of 4-NPA in laboratory animals.
Residue studie of total arsenic in turkey tissues indicate that arsenic concentrations increase following exposure of the animals to 4-NPA but decline to control levels after a 9-day withdrawal period. However, no data are given concerning the kinetics of 4-NPA residues in turkey tissues.
The limited data available give no indication of genotoxicity or carcinogenicity but no data at all are available on developmental and reproductive effects. A NOEL can not be firmly established but it would be approximately 2 mg 4-NPA kg-1 bw day-1, based on the chronic toxicity study in rats. However, there is evidence that dogs are maybe more sensitive to 4-NPA and a properly conducted study in dogs may give a lower NOEL. Additional studies would be needed in order to further refine the assessment of the consumer safety.
Since a NOEL cannot be confidently established from the available toxicity data an acceptable daily intake (ADI) value cannot be determined. The data available does not allow the FEEDAP Panel to propose maximum residue limit (MRL) values.
No validated control methods are supplied for 4-NPA in premixes and feedstuffs. Validated ontrol methods would be required for any marker residue when this can be established.