ALBENDAZOLE

Overview

Chemical Names
METHYL-5-PROPYLTHIO-1-H-BENZIMIDAZOL-2-YL-CARBAMATE
CAS number
54965-21-8
Functional Class
Veterinary Drug
ANTHELMINTHIC_AGENT

Evaluations

Evaluation year: 1989

ADI:
0-0.05 mg/kg bw

Comments:
Albendazole was evaluated at JECFA's 34th meeting. JECFA concluded that albendazole was non-carcinogenic in mice & non-genotoxic in multiple assay systems. The most significant toxicological effect was teratogenicity, limb defects in the rat being the most sensitive indicator of developmental toxicity. A composite NOEL of 5 mg/kg bw/day was derived from the results of a series of Segment II studies in Long-Evans rats. An ADI of 0-0.05 mg/kg bw was established based on this NOEL and a safety factor of 100. A safety factor of 100 was chosen for this compound after taking into consideration poor absorption in humans, rapid metabolism, the lack of teratogenic potential of most metabolites, the use of the drug in humans, and the identity of residues in food.
MRL Comment:
MRLs: Muscle and fat: 0.1 mg/kg; Liver and kidney: 5 mg/kg; Milk: 0.1 mg/l. Residues would be measured as the 2-aminosulfone metabolite & multiplied by a factor of 5 (cattle) or 6 (sheep).
MRL Code:
MRL
Meeting:
34
Report: 
TRS 788-JECFA 34/14
Tox Monograph: 
FAS 25-JECFA 34/3
Residues: 
FNP 41/2-JECFA 34/1
Addendum: 
FAS 25-JECFA 34/3

Toxicological study

Pivotal Study:
Segment II studies ((Killeen & Rapp, 1975e; Christian, 1984, 1987a; Killeen & Rapp, 1976; Christian, 1984, 1987a; Hogan & Rinehart, 1977; Schroeder & Rinehart, 1978):A series of studies in pregnant Long Evans rats (19-60/group) dosed on gestation days 6 to 15 & sacrificed on gestation day 20. Study A: 0, 2, 5, 10 or 30 mg/kg bw/d albendazole in 0.5% methylcellulose. At 30 mg/kg: high incidence of resorptions, reduced size, weight, micromelia, ectromelia, curved femur and microfetalis. Study B: 0, 0.5, 2, 5 or 10 mg/kg bw/d albendazole in 0.5% methylcellulose. At 10 mg/kg: reduced size and weight, retarded skeletal ossification, increased incidences of micromelia and microfetalis (which included shortened long bones in fore and hind limbs. Study C: 29% freeze dried liver, obtained from cattle 48 hours after a single oral dose of 0 or 27.5 mg/kg bw albendazole in diet (0.42 mg/kg bw/d albendazole equivalents). The only treatment-related observation: shortened limb bones, 2/248 treated fetuses from 2 different litters. A re-evaluation of these affected fetuses failed to confirm the above description. The apparent defects were described as artifacts caused by poor staining (Christian, 1987b). Study D: diets containing 10, 20 or 30% freeze dried liver from cattle 12 days after a single oral dose of 0 or 16.5 mg/kg bw albendazole (0.02, 0.04 and 0.06 mg/kg bw/d albendazole equivalents). 30% exposed liver: resorptions were increased, 9 of which were in 1 female. If data from this rat were eliminated there were no significant effects.
Animal Specie:
Rat
Effect:
micromelia, ectromelia, curved femur and microfetalis
NOEL:
5 mg/kg/d
LOEL:
10 mg/kg/d
Point of departure:
5 mg/kg bw/d