FLUBENDAZOLE

Overview

Chemical Names

[5-(4-FLUOROBENZOYL)-1H-BENZIMIDAZOL-2-YL]CARBAMIC ACID METHYL ESTER

Synonyms

FLUVERMAL; FLUBENOL; FLUMOXAL; FLUMOXANE

CAS number

31430-15-6

Functional Class

Veterinary Drug
ANTHELMINTHIC_AGENT

Evaluations

Evaluation year: 1993

ADI:
0-0.012 mg/kg bw

Comments:

An ADI of 0-12 µg/kg of body weight was established for flubendazole, based on the NOEL of 2.5 mg/kg bw/day in the 3-month study in dogs, and a safety factor of 200. This safety factor accounts for of the fact that the doses were administered only 6 days/week in this study, the precise consequences of which could not be assessed. The Committee noted that the ADI also provided a safety margin of about 1000 with respect to the NOEL of 10 mg/kg bw/day derived from the rat teratogenicity study. The Committee considered that further carcinogenicity studies would not be required, since the highest dose used in the negative studies that it had evaluated exceeded the ADI by a factor of approximately 2000.

MRL Comment:

MRLs (expressed as parent drug, in mg/kg): Muscle and liver (pigs): 0.010; Muscle (poultry): 0.2; Liver (poultry): 0.5; Eggs: 0.4

MRL Code:

MRL

Intake:

0.622 mg/p/d, based on observed residue levels in pig tissues & eggs

Meeting:

Report:

TRS 832-JECFA 40/10

Tox Monograph:

FAS 31-JECFA 40/3

Residues:

FNP 41/5-JECFA 40/21

Toxicological study

Pivotal Study:

3-month dog study (Marsboom et al., 1975): Beagles (3/sex/group) were given flubendazole orally as a powder in gelatin capsules at doses of 0, 2.5, 10 or 40 mg/kg bw/day, 6 days/week, over 3 months. Small-sized prostate and congestion of cauda of the epididymis were observed in all males at doses of 10 and 40 mg/kg bw/d. Non-dose-related atrophic changes of the prostate were noticed at the higher dose groups. Subsequent to the above report the histopathological slides were evaluated by two independent pathologists. Both experts agreed that the atrophic changes were not indicative of a treatment-related toxic effect and should be considered as incomplete development in sexually immature dogs (Thoonen, 1987; Powell, 1991). Because of the lack of conclusive evidence as to the etiology of these changes, the Committee concluded that the NOEL in this study was 2.5 mg/kg bw/day.

Animal Specie:

Dog

Effect:

Atrophic change in prostate

NOEL:

2.5 mg/kg bw/day

Point of departure: