Derquantel
Overview
Synonyms
2-desoxoparaherquamide, 2-deoxyparaherquamide, 2-DOPH, PF-00520904, PNU-141962
CAS number
187865-22-1
JECFA number
75
Functional Class
Veterinary Drug
VETERINARY_DRUG
VETERINARY_DRUG
Evaluations
Evaluation year: 2013
ADI: 0–0.3μg/kg bw
ADI:
0–0.3μg/kg bw
Comments:
The Committee maintained the ADI of 0–0.3μg/kg body weight established at its seventyfifth meeting (WHO TRS No. 969, 2011).
MRL Comment:
Recommended maxium residue limits (MRLs)
In sheep: 0.3 μg/kg (muscle); 0.8 μg/kg (liver); 0.4 μg/kg (kidney); 7.0 μg/kg (fat), as derquantel.
Intake:
There were insufficient data to calculate an estimated daily intake (EDI), and the theoretical maximum daily intake (TMDI) approach was used. Using the model diet and the marker residue to total residue ratio approach with the maximum residue limits (MRLs) recommended, the estimated dietary exposure is 6.8 μg/person, which represents approximately 38% of the
upper bound of the ADI.
Meeting:
78
Report:
Residues:
Evaluation year: 2011
ADI:
0–0.3 μg/kg bw
Comments:
The Committee considered the acute clinical observations in dogs, which were consistent with the antagonistic activity of derquantel on nicotinic acetylcholine receptors, as the most relevant toxicological effect for the establishment of an ADI. The Committee established an ADI of 0–0.3 μg/kg bw based on the LOAEL of 0.1 mg/kg bw/d and a total uncertainty factor of 300 (100-fold default uncertainty factor x 3 for using a LOAEL instead of a NOAEL). The Committee noted that the dog is more sensitive than the rat to the anti-nicotinergic effects of derquantel, but had no information to allow a relative comparison with
humans. Using the model diet and the ratio of the concentration of the marker residue to the concentration of the total residues
noted above, the MRLs for derquantel residues in sheep tissues result in a TMDI of 8 μg/person (45% of the ADI).
MRL Comment:
In sheep: 0.2 μg/kg (muscle); 2.0 μg/kg (liver); 0.2 μg/kg (kidney); 0.7 μg/kg (fat), as derquantel. No MRLs for sheep milk.
Intake:
TMDI of 8 μg/p/d, based on a model diet & concentration marker residue:concentration total residues
Meeting:
75
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
Study 1 (Savides, 2008): 90-day oral toxicity study, Beagles (4/sex/group; 6 months old) received neat derquantel by capsule at a dose of 0, 0.1, 0.5, 1 or 10 mg/kg bw/d. Test article–related clinical observations included dry mouth, dilated pupils, ptosis, dry conjunctiva, dry eyes, red eyes and relaxed nictitating membrane. Less commonly seen were vomit in thecage, salivation and abnormalities of faeces, and rarely seen were tremors and decreased activity. In general, these findings were first seen during the first week of dosing and occurred with a dose-related increase in numbers of animals affected, persistence of the finding post-dosing and number of days affected. Based on test article–related clinical signs at all dose levels, the LOAEL for this study is 0.1 mg/kg bw/d.
Study 2 (May, 2009b): GLP-compliant, 90-day oral toxicity study, Beagles (4/sex/group, 10.5–12 months old) were gavaged with derquantel in 1.0% (w/v) carboxymethylcellulose at a dose of 0, 0.1, 0.5, 1, or 5 mg/kg bw/d. Protruding nictitating membrane and dilated pupils were seen in all test article–treated groups, with a general dose-related increase in incidence and
number of animals affected. Based on observations of protruding nictitating membranes, dilated pupils, eye redness and decreased indirect pupillary light response at all dose levels, the LOAEL for derquantel was 0.1 mg/kg bw/d.
Animal Specie:
Dog
Effect:
Protruding nictitating membranes, dilated pupils, eye redness and decreased indirect pupillary light response
LOAEL:
0.1 mg/kg bw/d
Point of departure:
0.1 mg/kg bw/d (LOAEL)