FLOXASOL

Overview

Chemical Names
SARAFLOXACIN HYDROCHLORIDE; 6-FLUORO-1-(4-FLUOROPHENYL)-7-PIPERAZINYL-1,4-DIHYDRO-4-OXO-3-QUINOLINECARBOXYLIC ACID HYDROCHLORIDE
Synonyms
FLOXASOL
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT

Evaluations

Evaluation year: 1999

ADI:
0-0.33 µg/kg bw

Comments:
The Committee considered the microbiological effects of sarafloxacin to be the most sensitive and appropriate endpoint for establishment of an ADI. The upper limit of the ADI based on the antimicrobial activity of sarafloxacin was calculated as follows: ADI (µg/kg) = (0.125 µg/g (MIC50) × 220 g (mass colonic contents))/(0.70 (fractional bioavailability) × 2 (safety factor) × 60 kg (weight adult human)) = 0.33 µg/kg bw. The MIC50 in the formula is for three strains of human isolates of Peptostreptococcus spp., which was the most sensitive strain of the relevant bacteria of human GI microflora tested. The fraction of the dose available to act upon microorganisms in the colon was based on studies in humans in which approximately 70% of a 100-mg oral dose of sarafloxacin was not absorbed. A safety factor of 2 was used because of the limited MIC data available on the sensitive, relevant bacteria of the human gastrointestinal tract. This ADI provides a margin of safety of 17 000 when compared with the lowest toxicological NOEL of 5 mg/kg bw/day in the 90-day study in dogs.
MRL Comment:
MRLs (expressed as sarafloxacin, in mg/kg): Muscle (turkeys and chickens): 0.01; Liver and Kidney (turkeys and chickens): 0.08; Fat (turkeys and chickens): 0.02 (fat/skin in normal proportions)
Intake:
TMDI: 16 µg/p/d
Meeting:
50
Report: 
TRS 888-JECFA 50/33
Tox Monograph: 
FAS 41-JECFA 50/37
Residues: 
FNP 41/11-JECFA 50/107

Toxicological study

Pivotal Study:
In vitro microbiological assay (Prabhavathi, 1984): Minimum inhibitory concentrations (MICs) of sarafloxacin were determined against human clinical bacterial isolates. The quality and design were consistent with current scientific standards.
Animal Specie:
Human gut flora
Effect:
Growth inhibition
Point of departure:
0.125 µg/g (MIC50)