MOXIDECTIN

Overview

Chemical Names
SPIRO[11,15-METHANO-2H,13H,17H-FURO[4,3,2-PQ][2,6]-BENZODIOXACYCLO-OCTADECIN-13,2'[2H]PYRAN-17-ONE]-6'-[1,3-DIMETHYL-1-BUTENYL]-3',4',5',6,6',7,10,11,14,15,17a,20,20a,20b- DIHYDRO-4'-[METHOXYIMINO]-5',6,6,19-TETRAMETHYL-[6R-2aE,4E,4'E,5'S*,6R*,6'S*(E),8E, 11R* 13R*,15S*,17aR*,20R*,20aR*,20bS*]]-
Functional Class
Veterinary Drug
ANTHELMINTHIC_AGENT

Evaluations

Evaluation year: 1999

ADI:
0-2 µg/kg bw

Comments:
The Committee concluded that the most relevant effects for the toxicological evaluation of moxidectin were those observed in the 90-day study in dogs, where the NOEL was 0.3 mg/kg bw/day. Based on this NOEL and a safety factor of 200 to account for the uncertain sensitivity of the test system used to assess the neurotoxicity of moxidectin, the Committee established an ADI of 0-2 µg/kg bw for moxidectin, rounded to one significant figure. This ADI provides an adequate margin of safety for the effects noted in the reproductive toxicity studies in rats.
MRL Comment:
MRLs (as parent drug, in mg/kg): Muscle (cattle and deer): 0.02; Muscle (sheep): 0.05; Liver (cattle, sheep and deer): 0.1; Kidney (cattle, sheep and deer): 0.05; Fat (cattle, sheep and deer): 0.5. All MRLs were recommended at the 45th meeting, except for sheep muscle (47th meeting). At the 45th meeting the Committee noted the very high concentrations and great variation in the level of residues at the injection site in cattle over a 49-day period after dosing. Final MRLs for sheep were recommended at the 51st meeting.
MRL Code:
MRL/TMRL
Meeting:
50
Report: 
TRS 888-JECFA 50/19
Tox Monograph: 
FAS 36-JECFA 45/27 (1995)
Residues: 
FNP 41/11-JECFA 50/79

Toxicological study

Pivotal Study:
90-day dog study (Schulze, 1989b): Beagles (4/sex/group) were fed diets containing 0, 10, 30 or 60 mg moxidectin/kg of feed (0, 0.3, 0.9 or 1.6 mg/kg bw/day) for 90 days At the highest dose, lacrimation, tremors, salivation, slight ataxia and a languid appearance were noted. Dose-dependent reductions in absolute body weights and food consumption were noted in dogs given the two highest doses. High-dose females had decreased absolute heart weights, and high-dose males had decreased absolute pituitary and pituitary to brain weight ratios. The NOEL in this study was 0.3 mg/kg bw/day .
Animal Specie:
Dog
Effect:
Decreased bodyweight & feed consumption
NOEL:
0.3 mg/kg bw/day
Point of departure:
0.3 mg/kg bw/day
Previous Years:
1997, TRS 879-JECFA 48/6, FNP 41/10-JECFA 48/71, FAS 36-JECFA 45/27 (1995). 0-0.002 (1995). MRLs (EXPRESSED AS PARENT DRUG): MUSCLE (CATTLE): 0.02; MUSCLE (SHEEP): 0.05; LIVER (CATTLE AND SHEEP): 0.1; KIDNEY (CATTLE AND SHEEP): 0.05; FAT (CATTLE AND SHEE
1997, TRS 879-JECFA 48/6, FNP 41/10-JECFA 48/71, FAS 36-JECFA 45/27 (1995). 0-0.002 (1995). MRLs (EXPRESSED AS PARENT DRUG): MUSCLE (CATTLE): 0.02; MUSCLE (SHEEP): 0.05; LIVER (CATTLE AND SHEEP): 0.1; KIDNEY (CATTLE AND SHEEP): 0.05; FAT (CATTLE AND SHEE