TILMICOSIN

Overview

Chemical Names

(10E,12E)-(3R,4S,5S,6R,8R,14R,15R)-14-(6-DEOXY-2,3-DI-O-METHYL-b-d-ALLO-HEXOPYRANOSYOXYMETHYL)-5-(3,6-DIDEOXY-3-DIMETHYLAMINO-b-d-GLUCO- HEXAPYRANOSYLOXY)-6-[2-(cis-3,5-DIMETHYLPIPERIDINO)ETHYL]-3-HYDROXY-4,8,12- TRIMETHYL-9-OXOHEPTADECA-10,12-DIEN-15-OLIDE; 4A-O-DE(2,6-DIDEOXY-3-C-METHYL-alpha-L-RIBO-HEXOPYRANOSYL)-20-DEOXY-20-(3,5-DIMETHYL-1-PIPERIDINYL)-(20(cis:trans))

Synonyms

20-DEOXY-20-(3,5-DIMETHYLPIPERIDIN-1-YL)-DESMYCOSIN

CAS number

0108050-54-0

Functional Class

Veterinary Drug
ANTIMICROBIAL_AGENT

Evaluations

Evaluation year: 2008

ADI:
0–40 μg/kg body weight

Comments:

The Committee established an ADI of 0–40 μg/kg body weight at its 47th meeting, based on a NOEL of 4 mg/kg bw/day from a 12-month study in dogs and a safety factor of 100. An identical ADI would have been established using the data from the study on rats colonized with human intestinal microflora and a safety factor of 10 to account for variability among humans.

MRL Comment:

Recommended maximum residue limits (MRLs) for chicken of - Skin/Fat 250 (μg/kg), - Kidney 600 (μg/kg), - Liver 2400 (μg/kg), - Muscle 150 (μg/kg) and turkey of - Skin/Fat 250 (μg/kg), - Kidney 1200 (μg/kg), - Liver 1400 (μg/kg), - Muscle 100 (μg/kg) The Committee was not able to recommend a MRL for sheep milk. Before a re-evaluation of tilmicosin with the aim of recommending MRLs in tissues of rabbits, the Committee would require adequately designed residue studies with doses and routes of administration under authorized conditions of use and using a validated method suitable for the purpose.

Intake:

7 day withdrawal time, chicken tissues: 0.292 mg/p/d; turkey tissues: 0.211 mg/p/d

Meeting:

Report:

TRS 954-JECFA 70

Addendum:

FAO Monograph

Toxicological study

Pivotal Study:

12-month dog study (Jordan & Bernhard, 1989): Beagles (4/sex/group) were given 0, 4,12 or 36 mg/kg bw/day tilmicosin in capsules for 12 months. The daily dose was administered in two equal amounts, 6 hours apart. Peripheral redness was seen sporadically in some animals of all groups, in particular at 12 and 36 mg/kg bw/day. Body weight gains were lower at > 12 mg/kg bw/day. Heart rates were markedly increased at 36 mg/kg bw/day with sporadic depression of the ST segment in some dogs. Heart weight was increased at 36 mg/kg bw/day and four males and one female at this dose showed enlarged hearts. The NOEL was 4 mg/kg bw/day .

Animal Specie:

Dog

Effect:

Decreased bodyweight gains & peripheral redness

NOEL:

4 mg/kg bw/d

LOEL:

12 mg/kg bw/d

Point of departure:

4 mg/kg bw/d

Evaluation year: 2000

ADI:

0-0.04 mg/kg bw (1996)

MRL Comment:

The Committee was not able to recommend a MRL for sheep milk.

MRL Code:

MRL/TMRL

Meeting:

Report:

TRS 900-JECFA 54/29

Tox Monograph:

FAS 38-JECFA 47/109 (1996)

Previous Years:

1996, TRS 876-JECFA 47/37, FNP 41/9-JECFA 47/105, FAS 38-JECFA 47/109. MRLs (EXPRESSED AS PARENT DRUG): MUSCLE (CATTLE, PIGS AND SHEEP): 0.1; LIVER (CATTLE AND SHEEP): 1; LIVER (PIGS): 1.5; KIDNEY (CATTLE AND SHEEP): 0.3; KIDNEY (PIGS): 1; FAT (CATTLE, P