CLOSANTEL

Overview

Chemical Names
N-[5-CHLORO-4-[(4-CHLOROPHENYL)CYANOMETHYL]-2-METHYLPHENYL]-2-HYDROXY-3,5- DIIODOBENZAMIDE
Synonyms
FLUKIVER; SEPONVER
CAS number
57808-65-8
Functional Class
Veterinary Drug
ANTHELMINTHIC_AGENT

Evaluations

Evaluation year: 1993

ADI:
0-0.03 mg/kg bw

Comments:
An ADI of 0-0.03 mg/kg bw/d (1.8 mg/p/d for a 60-kg adult) was established for closantel based on the NOEL of 2.5 mg/kg bw/d from a carcinogenicity study in rats and a safety factor of 100. Based on this ADI, the Committee established the following MRLs (in mg/kg): Muscle and liver (sheep): 1.5; Kidney (sheep): 5; Fat (sheep): 2; Muscle and liver (cattle): 1; Kidney and fat (cattle): 3. The estimated maximum daily intake at MRLs of 1.75 mg/p/d is less than the ADI of 1.8 mg/p/d.
MRL Comment:
MRLs (in mg/kg): Muscle and liver (sheep): 1.5; Kidney (sheep): 5; Fat (sheep): 2; Muscle and liver (cattle): 1; Kidney and fat (cattle): 3
MRL Code:
MRL
Intake:
Estimated maximum daily intake at MRLs: 1.05 mg/p/d for sheep, 1.7 mg/p/d for cattle
Meeting:
40
Report: 
TRS 832-JECFA 40/7
Tox Monograph: 
FAS 27-JECFA 36/3 (1990)
Residues: 
FNP 41/5-JECFA 40/1

Toxicological study

Pivotal Study:
2-year dietary carcinogenicity study (Verstraeten et al., 1981b): Wistar rats (n=50/sex/group) were fed diets containing 0, 25, 100 and 400 mg/kg (0, 2.5, 10, 40 mg/kg bw/d) closantel for 24 months. Mortality was slightly increased in high dose females, with no effect in males. Increased incidences of spermatic granulomas were noted in the 10 and 40 mg/kg b.w./day dosed males. An increase in the vacuolization of the optic nerve was observed in the high-dose males and females. The NOEL in this study was 2.5 mg/kg bw/day.
Animal Specie:
Rat
Effect:
Increased incidences of sperm granulomas in the epididymes of male rats
NOEL:
2.5 mg/kg bw/day
Point of departure:
2.5 mg/kg bw/day
Previous Years:
1990, TRS 799-JECFA 36/18, FNP 41/3-JECFA 36/32, FAS 27-JECFA 36/3. 0-0.03. MRLs: EDIBLE TISSUES OF SHEEP: 1.5; BOVINE TISSUES: MUSCLE: 0.5 (TEMPORARY), KIDNEY: 2 (TEMPORARY), LIVER: 1 (TEMPORARY). FU. MRL/TMRL
1990, TRS 799-JECFA 36/18, FNP 41/3-JECFA 36/32, FAS 27-JECFA 36/3. 0-0.03. MRLs: EDIBLE TISSUES OF SHEEP: 1.5; BOVINE TISSUES: MUSCLE: 0.5 (TEMPORARY), KIDNEY: 2 (TEMPORARY), LIVER: 1 (TEMPORARY). FU. MRL/TMRL