Summary of the changes to nicarbazin products
Nicarbazin is a coccidiostat, which is mixed with feed for broiler chickens for the prevention and control of coccidiosis caused by Eimeria spp. Nicarbazin is a 1:1 molar mixture of 4,4'-dinitrocarbanilide (DNC) and 4,6-dimethyl-2-hydroxypyrimidine (HDP). In 2006, nicarbazin was nominated for review because of:
- death of broiler chickens from accidental overdosing of the coccidiostat
- concerns raised about its residue definition
- concerns raised about the dietary risk for humans who eat treated chickens.
For the consideration of the nomination of nicarbazin, the APVMA:
- commissioned the Office of Chemical Safety and Environmental Health (OCSEH) to investigate the toxicological concerns with nicarbazin
- conducted a survey to find out how nicarbazin was used and the possible risks that the use of the chemical may pose
- conducted a residue assessment to consider whether or not OCSEH's recommendations warranted a revision to the existing MRLs, withholding periods and dietary exposure estimates for nicarbazin
- revisited the residue definition of nicarbazin, which was 'nicarbazin'.
These actions led to the recommendations to:
- revise the acceptable daily intake (ADI) for nicarbazin from 2 mg/kg bw/day to 0.4 mg/kg bw/day
- establish an acute reference dose (ARfD) of 0.4 mg/kg bw
- establish new safety directions for nicarbazin-only products
- confirm existing safety directions for nicarbazin in combination with narasin and maduramicin ammonium are adequate
- revise the residue definition from 'nicarbazin' to "4,4'-dinitrocarbanilide (DNC)"
- revise the MRLs to 35 mg/kg for chicken liver, 20 mg/kg for chicken kidney; 5 mg/kg for chicken muscle and 10 mg/kg for chicken skin/fat
- reduce the withholding period for nicarbazin-only products from four days to 1 day at an inclusion of 125 ppm in feed; for the nicarbazin + maduramicin ammonium product from one day to zero days at an inclusion of 40 ppm nicarbazin + 3.75 ppm maduramicin ammonium in feed; and for the nicarbazin + narasin product from one day to zero days at an inclusion of 50 ppm nicarbazin + 50 ppm narasin
- retain the existing restriction from administering nicarbazin to chickens that will lay eggs for human consumption
- conclude that the chronic and acute dietary exposures to nicarbazin would be acceptable under the new standards.
The survey highlighted the important role of nicarbazin in controlling coccidiosis and confirmed that exposure to nicarbazin on farms and in feed mills was limited because of mechanisation of the feed milling, delivery and feeding operations.
Since these recommendations only required relatively minor changes to the product labels, the APVMA decided to give effect to the recommendations through the registration process rather than proceeding to a formal review. Registrants accepted the APVMA’s invitation to amend their labels voluntarily with the safety directions and withholding periods proposed in the toxicology and residue reports. All nicarbazin product labels have been updated and registrants requested the APVMA to cancel all previous label approvals for these products. The MRL Standard was amended with the new MRLs, with action to make corresponding amendments to the Food Standards Code.
For more information, see a detailed history of the nicarbazin assessment.