ADVOCIN®

Comments:

Danofloxacin belongs to a group of fluoroquinolones active against aerobic gram-negative bacteria; human gastrointestinal flora are largely unaffected by these compounds. Therefore, the Committee decided to base the ADI on toxicity, not on its effects on the intestinal flora. Moreover, the toxicological end-point resulted in a lower ADI. The Committee established an ADI of 0-20 µg/kg bw/d (rounded to one significant figure) based on the NOEL of 2.4 mg/kg bw/d for arthropathy in a 3-month study in immature dogs and a safety factor of 100. The Committee noted that the NOEL for arthropathy in studies with desmethyldanofloxacin was 0.25 mg/kg bw/day. As dogs that received oral doses of danofloxacin were also exposed to the metabolite desmethyldanofloxacin, the Committee concluded that a separate ADI for desmethyldanofloxacin was unnecessary. However, the approximately 10-fold higher toxicity of the metabolite should be taken into account when recommending MRLs, as consumers may be directly exposed to desmethyldanofloxacin in liver.

MRL Comment:

MRLs (in mg/kg, total residues as danofloxacin): Muscle (cattle and chickens): 0.2; Muscle and fat (pigs): 0.1; Liver and kidney (cattle and chickens): 0.4; Liver (pigs): 0.05; Kidney (pigs): 0.2; Fat (cattle): 0.1; Fat/skin in normal proportion (chickens): 0.1. Total residues = danofloxacin residues + unidentified residues as danofloxacin equivalents + residues of desmethyldanofloxacin as danofloxacin equivalents.

MRL Code:

MRL

Intake:

TMDI as danofloxacin equivalents: 0.28 mg/p/d

Meeting:

48

Report: 

Tox Monograph: 

Residues: