ABAMECTIN

Overview

Chemical Names

AVERMECTIN B1a: (2aE,4E,8E)-(5'S,6S,6'R,7S,11R,13S,15S,17aR,20R,20aR,20bS)-6'-[(S)-sec-BUTYL]-5',6,6',7,10,11,14,15,17a,20,20a,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]BENZODIOXA-CYCLOOCTADECIN-13,2'-[2H]PYRAN]-7-YL 2,6-DIDEOXY-4-O-(2,6-DIDEOXY-3-O-METHYL-alpha-L-ARABINO-HEXOPYRANOSYL)-3-O-METHYL-alpha-L-ARABINO-HEXOPYRANOSIDE; AVERMECTIN B1b: (2aE,4E,8E)-(5'S,6S,6'R,7S,11R,13S,15S,17aR,20R,20aR,20bS)-5',6,6',7,10,11,14,15,17a,20,20a,20b-DODECAHYDRO-20,20b-DIHYDROXY-6'-ISOPROPYL-5',6,8,19-TETRAMETHYL-17-OXOSPIRO[11,15-METHANO-2H,13H,17H-FURO[4,3,2-pq][2,6]BENZODIOXA- CYCLOOCTADECIN-13,2'-[2H]PYRAN]-7-YL 2,6-DIDEOXY-4-O-(2,6-DIDEOXY-3-O-METHYL-alpha-L-ARABINO-HEXOPYRANOSYL)-3-O-METHYL-alpha-L-ARABINO-HEXOPYRANOSIDE

Synonyms

5-O-DEMETHYLAVERMECTIN A1a; 5-O-DEMETHYL-25-DE(1-METHYLPROPYL)-25(1-METHYLETHYL) AVERMECTIN A1a

CAS number

0065195-55-3

Functional Class

Veterinary Drug
ANTHELMINTHIC_AGENT

Evaluations

Evaluation year: 1998

ADI:
0-0.001 mg/kg bw

Comments:

ADI of 0-1 µg/kg bw/d (60 µg/p/d for a 60-kg human) established for veterinary use by the September, 1995 JMPR meeting, based on a NOAEL of 0.12 mg/kg bw/d from a reproductive toxicity study and a safety factor of 100. This ADI was revised from the former ADI value of 0-0.2 µg/kg bw/d after JMPR concluded that residues of the teratogenic delta-8,9-photolysis product would not be present in tissues. At the recommended MRLs of 0.1 mg/kg in liver & fat and 0.05 mg/kg in kidney, the maximum daily intake of avermectin B1a would be 49 µg/p/d, which gives an acceptable margin of safety between this value and the ADI of 60 µg/p/d.

MRL Comment:

MRLs (as avermectin B1a in liver and fat (cattle): 0.1 mg/kg; Kidney (cattle): 0.05 mg/kg. The Committee concluded that there was no need for an MRL for bovine muscle, since abamectin residues are below detectable levels at the recommended withdrawal time. As abamectin is intended only for use in beef cattle, there was also no need for an MRL for milk.

Intake:

49 µg/p/d for the summed MRLs for avermectin B1a in liver, kidney, & fat

Meeting:

Report:

TRS 876-JECFA 47/18

Tox Monograph:

JMPR 1992 evaluation

Residues:

FNP 41/9-JECFA 47/1

Toxicological study

Pivotal Study:

Two-generation study in rats (Gordon et al., 1982n): Crl:COBSTMCDTM(SD) BR rats (30/sex/group) were gavaged with 0, 0.05, 0.12 or 0.4 mg abamectin/kg bw/day. F0 and F1b rats were mated to produce F1a and F1b litters, F2a and F2b litters. During the lactation periods of both generations effects in the 0.4 mg/kg bw/day group: increased pup mortality, reduced viability and lactation indices, lower average pup body- weights, & increased incidence of pups which appeared thin and weak. Histopathological examination showed retinal anomalies in 3/4 males and 1/5 females in the high-dose group compared wich 1/10 in the control group (F1b weanlings). The anomalies consisted of single or multiple retinal folds of many layers that included pigment epithelium.

Animal Specie:

Rat

Effect:

During lactation periods F1 & F2: Increased pup mortality, decreased pup viability & bodyweîght, decreased lactation index, increased incidences of retinal folds.

NOAEL:

0.12 mg/kg bw/d

LOAEL:

0.4 mg/kg bw/d

Point of departure:

0.12 mg/kg bw/d

Previous Years:

1995, TRS 864-JECFA 45/7, FNP 41/8-JECFA 45/1. N. NO MRLs RECOMMENDED 1994, JMPR REPORT, FAO PLANT PRODUCTION AND PROTECTION PAPER, No. 127, ROME, 1994 1992, JMPR REPORT, FAO PLANT PRODUCTION AND PROTECTION PAPER, No. 116, ROME, 1993

Overview

Evaluations

Evaluation year: 1998

ADI:0-0.001 mg/kg bw

Toxicological study

ADI:
0-0.001 mg/kg bw