Pesticide residues in food — 2006: Toxicological ... - ipcs inchem

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All pivotal studies with bifenazate were certified as complying with good laboratory practice
(GLP).
Figure 1. Chemical structure of bifenazate
CH 3
*
O
NH
NH
O
O
CH 3
CH
CH 3
* Position of the bifenazate radiolabel used in the pharmacokinetic studies in rats
Evaluation for acceptable daily intake
1. Biochemical aspects: absorption, distribution, and excretion
Rats
The position of the radiolabel on bifenazate used in absorption, distribution, metabolism and
excretion studies is shown in Figure 1.
In a dose range-finding study, groups of two male and two female fasted Sprague-Dawley
rats were treated with [methoxyphenyl U-ring 14 C]bifenazate (lot No. CSL-94-516-73-20; purity,
> 98%) in corn oil at 10 or 1000 mg/kg bw by gavage. Rats were housed individually in glass
metabolism cages with food and water freely available. Dose preparations were analysed for chemical
concentration and radiochemical purity by high pressure liquid chromatography (HPLC). Expired air
from each animal passed through two trapping vessels that contained 40% (w/v) potassium hydroxide
(KOH) and water (to trap carbon dioxide) and one trapping tube that contained Chromosorb (to
trap radiolabelled volatile organic compounds). The trapping vessels were placed in a dry-ice bath.
Expired air, urine and faeces were collected at intervals after dosing for 168 h, with cage washes
done at the same intervals. At the end of the collection period, rats were killed and blood collected.
Carcasses were weighed, homogenized and analysed. All samples were analysed for radioactivity by
liquid scintillation counting (LSC).
The recovery of radiolabel was 93.77% and 100.85% of the administered dose of 10 and
1000 mg/kg bw, respectively. Radioactivity in the expired air was 0.21% and 0.6% of the 10 and
1000 mg/kg bw doses, respectively. Excretion via urine made up 12.4% of the dose at 10 mg/kg
bw and 4.79% at 1000 mg/kg bw. Urinary excretion was 96% complete after 72 h at 10 mg/kg
bw, and 61% complete after 72 h at 1000 mg/kg bw. Faecal excretion accounted for 68.9% of the
administered dose at 10 mg/kg bw, and 91.6% at 1000 mg/kg bw. At 10 mg/kg bw, faecal excretion
was 95% complete after 48 h, and at 1000 mg/kg, 61% complete at 72 h. Overall, more than 90%
of excretion (via all routes) was complete after 72 h at 10 mg/kg bw, and after 96 h at 1000 mg/ kg
bw. At 168 h after dosing, blood accounted for 0.13% of the dose at 10 mg/kg bw and 0.14% at
1000 mg/ kg bw. Concentrations in the carcass were 0.55% of the dose at 10 mg/kg bw and 0.33% of
the dose at 1000 mg/kg bw (Andre & McClanahan, 1997).
BIFENAZATE X-X JMPR 2006