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

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In the main study, which complied with GLP, the balance and excretion patterns of 2-quinoline
ring-labelled quinoxyfen and the amount of residual radioactivity in blood, organs and tissues were
determined after the following dosing regimen:
— a single oral dose at 10 mg/kg bw after jugular-vein cannulation;
— a single oral dose at 500 mg/kg bw after jugular-vein cannulation;
— 14 repeated daily oral doses of unlabelled quinoxyfen at 10 mg/kg bw followed by a single dose
of radiolabelled quinoxyfen at at 10 mg/kg bw, after jugular-vein cannulation;
— a single oral dose at 10 mg/kg bw after bile-duct cannulation; or
— a single oral dose at 500 mg/kg bw after bile-duct cannulation.
The jugular-vein cannulated rats (five males and five females per group) were killed at 48 h
after dosing. The bile-duct cannulated rats (three males per group) were killed at 24 h after dosing.
Blood samples were taken from the jugular cannulae at 0.25, 0.5, 0.75, 1, 1.5, 3, 6, 12, 24 and 48 h.
Urine, faeces and bile were collected regularly throughout the study.
Table 2 Balance of radioactivity and excretion patterns in rats 48 h after dosing with
14
C-quinoline-labelled quinoxyfen
Sample
Radioactivity (% of administered dose)
Single dose (mg/kg bw)
Repeated doses a (mg/kg bw)
10 500 10 10
Male Female Male Female Male Female
Urine 14.76 16.95 13.91 13.40 15.85 19.71
Faeces 78.28 71.53 67.97 69.64 74.19 72.43
Final cage wash 0.58 0.55 0.26 0.79 1.20 0.64
Expired 14 CO 2
NA NA 0.25 0.24 NA NA
Tissues/carcass 1.82 2.63 5.45 7.17 1.33 1.70
Contents of
0.72 2.74 1.97 2.02 0.79 0.94
gastrointestinal tract
Total 96.16 94.41 89.81 93.27 93.37 95.42
From Schumann et al. (1995)
NA, not analysed.
a
Fourteen doses of unlabelled quinoxyfen followed by a single dose of radiolabelled quinoxyfen.
Peak plasma radioactivity (C max
) was detected at approximately 0.5 h (2–3 μg equiv./g)
at 10 mg/kg bw and approximately 1.5 h (80–90 mg equiv./g) at 500 mg/kg bw. The elimination of
plasma radioactivity followed a biphasic pattern with half-lives (t½) for the rapid and slow phases
for the dose at 10 mg/kg bw of < 1 h and 15–19 h respectively, and 2–3 h and 18–22 h for the dose at
500 mg/kg bw. There were no significant differences between the repeat-dose and single-dose groups.
The elimination of radioactivity from blood followed a similar pattern. The area-under-the-curve
(AUC) of the plasma versus time graph for the elimination of radiolabel in plasma (0–48 h) was 22.3,
27.3 and 922 μg equiv. h/g in males and 30.4, 29.6 and 963 μg equiv. h/g in females after treatments
with a single radiolabelled dose, a single radiolabelled dose after repeated dosing and 500 mg/kg bw
14
C-quinoxyfen respectively.
By 24 h after dosing, 68–85% of the administered radioactivity had been recovered in the faeces
and urine, indicating rapid elimination from the body. After 48 h, 90-96% of the administered
14
C-quinoline ring-labelled quinoxyfen was recovered in the urine, faeces, cage wash and tissues
(Table 2). The faeces represented the major route of elimination as 68–78% of the administered dose
was eliminated via this route in 48 h, while 13–20% was eliminated in the urine. Urinary half-lives
QUINOXYFEN X-X JMPR 2006