EPRINOMECTIN

Overview

Chemical Names

EPRINOMECTIN B1a:- (2AE,4E,5'S,8E,11R,13S,171R,20aR,20bS)-6'-[(S)-sec-BUTYL]-5',6,6'7,10,11,14,15,17a,20a,20b-DODECAHYDRO-20-,20b-DIHYDROXY-5',6,8,19-TETRAMETHYL-17-OXOSPIRO-[11,15,METHANO-2H,13H,17H-FURO[4,3,2-pq][2,6]BENZODIOXACYCLO-OCTADECIN-13,2'-[2H]PYRAN-7-YL-4-O-(4-ACETAMIDO-2,4,6-TRIDEOXY-3-O-METHYL-a-L-lyxo-HEXOPYRANOSYL)-2,6-DIDEOXY-3-O-METHYL-a-L-arabino-HEXANOPYRANOSIDE (IUPAC) (4"R)-4"-ACETYLAMINO)-5-O-DEMETHYL-4"-DEOXYAVERMECTIN A1a (CAS); EPRINOMECTIN B1b:- (2AE,4E,5'S,8E,11R,13S,171R,20aR, 20bS) - 5',6,6'7,10,11,14,15,17a,20,20a,20-DODECAHYDRO-2-,20b-DIHYDROXY-6'-ISOPROPYL-5',6,8,19-TETRAMETHYL-17-OXOSPIRO-[11,15,METHANO-2H,13H,17H-FURO[4,3,2-pq][2,6]BENZODIOXACYCLO-OCTADECIN-13,2'-[2H]PYRAN-7-YL-4-O-(4-ACETAMIDO-2,4,6-TRIDEOXY-3-O-METHYL-a-L-lyxo-HEXOPYRANOSYL)-2,6-DIDEOXY-3-O-METHYL-a-L-arabino-HEXANOPYRANOSIDE (IUPAC) (4"R)-4"-ACETYLAMINO)-5-O-DEMETHYL-25-DE-(1-METHYL-PROPYL)-4"-DEOXY-25-(1-METHYLETHYL)AVERMECTIN A1a (CAS)

Functional Class

Veterinary Drug
ANTHELMINTHIC_AGENT

Evaluations

Evaluation year: 1999

ADI:
0-0.01 mg/kg bw

Comments:

The Committee considered that the most relevant effect for evaluating the safety of residues of eprinomectin is the effect on the mammalian nervous system. An ADI of 0-10 µg/kg bw was established on the basis of the NOEL of 1 mg/kg bw/d for mydriasis and focal neuronal degeneration in the brain in the one-year study in dogs and a safety factor of 100.5.

MRL Comment:

MRLs (expressed as eprinomectin B1a, in mg/kg tissue, mg/l milk): Muscle (cattle): 0.1; Liver (cattle): 2; Kidney (cattle): 0.3; Fat (cattle): 0.25; Milk (cattle): 0.02

Intake:

TMDI (as eprinomectin equivalents): 0.356 mg/p/d

Meeting:

Report:

TRS 888-JECFA 50/4

Tox Monograph:

FAS 41-JECFA 50/3

Residues:

FNP 41/11-JECFA 50/31

Toxicological study

Pivotal Study:

One-year GLP-compliant oral dog study (Kloss et al., 1994): Beagles (4/sex/dose) received eprinomectin by gavage at doses of 0, 0.5, 1, or 2 mg/kg bw/d in 0.5% aqueous methylcellulose. Signs noted at the highest dose included: mydriasis, slight focal degeneration of one to three neurons per dog in the pons area and/or the cerebellar nuclei in three of eight dogs. This degenerative change was characterized by neuronal enlargement resulting from increased eosinophilic, vacuolated cytoplasm with nuclear displacement. The NOEL was 1 mg/kg bw/d on the basis of mydriasis and focal neuronal degeneration in the brain.

Animal Specie:

Dog

Effect:

Mydriasis and focal neuronal degeneration

NOEL:

1 mg/kg bw/d

LOAEL:

2 mg/kg bw/d

Point of departure: