EPROFIL

Overview

Chemical Names
2-(4-THIAZOLYL)-1H-BENZIMIDAZOLE; 4-(2-BENZIMIDAZOLYL)THIAZOLE
Synonyms
THIABENDAZOLE; OMNIZOLE; THIABEN; THIBENZOLE; BOVIZOLE; EPROFIL; EQUIZOLE; MINTEZOL; MERTECT; LOMBRISTOP; MINZOLUM; NEMAPAN; POLIVAL; TBZ
CAS number
148-79-8
Functional Class
Veterinary Drug
ANTHELMINTHIC_AGENT

Evaluations

Evaluation year: 2002

ADI:
0-0.1 mg/kg bw

Comments:
Emesis and effects on the kidney, haematopoietic system, and development were considered relevant end-points for establishing an acute RfD. The most sensitive effect was histopathological changes in the spleen and bone marrow indicative of anaemia, for which almost identical NOELs were found in rats and dogs. Using the NOEL from the dogs study of 10 mg/kg bw/d and a safety factor of 100, the Committee established an acute RfD of 100 µg/kg bw, the same value as the ADI, which is based on a NOEL of 10 mg/kg bw/d for reduced weight gain in a 2-year dietary study in rats and a 100-fold safety factor. In view of the lack of appropriate data for this effect after single doses, the acute RfD is based on data from studies of repeated administration and hence may be conservative.
MRL Comment:
The MRLs (as tiabendazole + 5-hydroxytiabendazole) recommended at the fortieth meeting were not reconsidered and were maintained: 0.1 mg/kg, all edible tissues of cattle, goats, pigs, & sheep & milk of cattle & goats.
MRL Code:
MRL
Tolerable Intake:
100 µg/kg bw (acute RfD)
Meeting:
58
Report: 
TRS 911-JECFA 58/12
Tox Monograph: 
FAS 49-JECFA 58/11
Residues: 
FNP 41/5-JECFA 40/41 (1992)

Toxicological study

Pivotal Study:
Acute RfD--1-year dog study (Lankas, 1993): Beagles (4/sex/group) received tiabendazole orally in gelatin capsules at a daily dose of 0, 10, 40 or 160 mg/kg bw for 1 year. The following effects were noted at the high dose: emesis, decreased erythrocyte count, haemoglobin concentration and erythrocyte volume fraction, and increased activated partial thromboplastin time and platelet count. Dose-related increases in the frequency of renal distal tubule vacuolation (females); splenic haemosiderin deposition (females) were noted. Dose-related increase in splenic erythropoiesis occurred in animals at the two higher doses. Increased bone-marrow erythropoiesis was seen only in females at the highest dose. The Committee at its previous meeting identified a NOEL of 10 mg/kg bw/day on the basis of (histopathological) changes indicative of haemolytic anaemia. ADI (Woodard, 1964)--Charles River rats (35/sex/group) were fed dietary levels adjusted to provide 0, 10, 40 or 160 mg/kg bw/day of tiabendazole for two years. At the highest dose, decreased weight gain (25%), food consumption, and haemoglobin and haematocrit values were noted. Slightly decreased bodyweight gain was noted in male rats at 40 mg/kg bw/d. The NOEL was 10 mg/kg bw/day .
Animal Specie:
Dog (RfD); rat (ADI)
Effect:
Histopathological changes in the spleen and bone marrow indicative of anaemia (RfD); reduced bodyweight gain (ADI)
NOEL:
10 mg/kg bw/day
LOEL:
40 mg/kg bw/d
Point of departure:
10 mg/kg bw/d (ADI & RfD)
Previous Years:
1997, TRS 879-JECFA 48/8, FNP 41/5-JECFA 40/41 (1992), FAS 39-JECFA 48/3. 0-0.1 mg/kg bw (1992). THE MRLs RECOMMENDED AT THE FORTIETH MEETING (1992) WERE MAINTAINED. FU. MRL 1992, TRS 832-JECFA 40/21, FNP 41/5-JECFA 40/41, FNP 31-JECFA 40/37. 0-0.1. MRL
1997, TRS 879-JECFA 48/8, FNP 41/5-JECFA 40/41 (1992), FAS 39-JECFA 48/3. 0-0.1 mg/kg bw (1992). THE MRLs RECOMMENDED AT THE FORTIETH MEETING (1992) WERE MAINTAINED. FU. MRL 1992, TRS 832-JECFA 40/21, FNP 41/5-JECFA 40/41, FNP 31-JECFA 40/37. 0-0.1. MRL