LEVAMISOLE

Overview

Chemical Names
(-)-(S)-2,3,5,6-TETRAHYDRO-6-PHENYLIMIDAZO[2,1-b]THIAZOLE MONOHYDROCHLORIDE (ALSO USED AS FREE BASE AND PHOSPHATE)
Synonyms
ERGAMISOL; LEVAMISOLE HYDROCHLORIDE; TETRAMISOLE; NEMICIDE; STIMAMIZOL; SOLASKIL; TRAMISOL; WORM-CHEK
CAS number
16595-80-5 (L-FORM HYDROCHLORIDE)
Functional Class
Veterinary Drug
ANTHELMINTHIC_AGENT

Evaluations

Evaluation year: 1995

ADI:
0-6 µg/kg bw

Comments:
Further studies reviewed at the present meeting provided information on the incidence and mechanisms of the haematological effects in humans and dogs. The Committee recognized that while continuous dosing of dogs with 1.25 mg/kg bw/day did not result in haemolytic anaemia, this dose did cause the re-emergence of haemolytic anaemia in a number of dogs previously sensitized with 20 mg/kg bw/day of levamisole. Since there is a very small population of humans who are sensitized to levamisole following therapeutic exposure, the Committee concluded that the use of a safety factor of 200 would be appropriate. On this basis, an ADI of 0-6 µg/kg bw was established.
MRL Comment:
MRLs (expressed as parent drug, in mg/kg): Muscle, kidney and fat (cattle, sheep, pigs and poultry): 0.01; Liver (cattle, sheep, pigs and poultry): 0.1; Milk: previous temporary MRL withdrawn; Eggs: no MRL allocated (should not be used in lactating cows or laying hens)
MRL Code:
MRL
Intake:
TMDI for parent drug + equivalents: 0.397 mg/p/d (0.014 mg/p/d as parent drug), considered equal to the ADI in view of the inherent variability in estimating total equivalent residues & the fact that only a small proportion of total residues is used to estimate total equivalents.
Meeting:
42
Report: 
TRS 851-JECFA 42/7
Tox Monograph: 
FAS 33-JECFA 42/3
Residues: 
FNP 41/6-JECFA 42/39

Toxicological study

Pivotal Study:
14-month dog study with immunotoxicology study follow-up of same study animals (Verstraeten et al., 1993b; Moeremans & Bols, 1993b): Beagles (n=50) were given levamisole in gelatin capsules for varying periods during a 14-month study at doses of 1.25, 2.5, or 20 mg/kg bw/d. Twenty-three sensitized animals from this phase were then challenged with 1.25, 2.5, and 20 mg/kg bw/day levamisole (Intervals IV, V and VI). Blood was collected weekly and 24 hours after the last dose at each treatment level. Erythrocytes from treated dogs were incubated with specific antisera, anti-dog IgG, anti-dog IgM, anti-dog C3 and anti-dog C3c, for the determination of antibodies or complement on cell surfaces. Dose-responsive anemia was produced at all challenge doses, with serological positivity noted beginning at 2.5 mg/kg challenge dose.
Animal Specie:
Dog
Effect:
Re-emergence of haemolytic anaemia
LOEL:
1.25 mg/kg bw/day
Point of departure:
1.25 mg/kg bw/day
Previous Years:
1990, TRS 799-JECFA 36/31, FNP 41/3-JECFA 36/65, FAS 27-JECFA 36/75. 0-0.003 (TEMPORARY). MRL (TEMPORARY): EDIBLE TISSUES AND MILK (ALL SPECIES): 0.01. TE. TMRL
1990, TRS 799-JECFA 36/31, FNP 41/3-JECFA 36/65, FAS 27-JECFA 36/75. 0-0.003 (TEMPORARY). MRL (TEMPORARY): EDIBLE TISSUES AND MILK (ALL SPECIES): 0.01. TE. TMRL