Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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The excretion of radioactivity in rats given a single oral dose of [ 14 C]zoxamide followed
similar patterns, with a higher (approximately threefold) proportion in the urine at the lower dose
(Table 1). More than 85% of the administered radioactivity was excreted during the first 24–48 h
after dosing. The major route for the elimination of radiolabel was in the faeces, which contained
74–92% of the administered dose. The remaining radioactivity (4–27%) was excreted in the urine,
with females tending to have a higher level of urinary excretion than males. A significant proportion
of the absorbed dose (approximately 45%) was excreted in the bile. Biliary excretion of radioactivity
in rats given [ 14 C]zoxamide as a single oral dose at 10 mg/kg bw was rapid. Most of the dose was
recovered within 12 h after dosing. Based on the recovery of radioactivity from the bile, blood, urine,
tissues and carcasses, 59–63% of the administered oral dose of [ 14 C]zoxamide was considered to be
systemically absorbed. Very little radioactivity remained in tissues (0.04–0.17% of the administered
dose) or carcass (0.34–1.9% of the administered dose) at 5 days after dosing, indicating that zoxamide
has a low potential for accumulation. No radioactivity was recovered as either 14 CO 2
or volatile
organic compounds. Pre-treatment of animals with diets containing non-radiolabelled zoxamide for
2 weeks or with five daily doses of radiolabelled zoxamide did not significantly alter the absorption
Table 1. Recovery of radiolabel in excreta, blood, tissues and residual carcass of rats treated with
radiolabelled zoxamide
Group
Dose
(mg/kg
bw)
Route a Sex Time of sacrifice Recovery (% of administered dose)
Urine d Bile Faeces Blood Tissues Carcass Total e
2 1000 Oral Male 7 days 6.4 — 94.1 0.01 0.02 0.30 100.9 f
Female 7 days 11.2 — 84.4 0.01 0.02 0.33 96.0 f
C 1000 Oral Male 5 days 3.5 — 92.4 0.00 0.04 0.34 96.2
D 1000 Oral Female 5 days 8.1 — 88.8 0.01 0.05 0.55 97.5
A 10 Oral Male 5 days 10.3 — 87.8 0.01 0.16 1.86 100
B 10 Oral Female 5 days 26.8 — 73.5 0.02 0.17 1.87 102.4
Q 10 Oral (bile); Male 72 h 9.5 45.8 32.2 0.01 0.18 2.98 90.8 g
bile-duct
cannulated
R 10 Oral (bile) Female 72 h 12.0 47.8 33.9 0.01 0.14 2.79 96.7 g
bile-duct
cannulated
E 10 Oral, pulse b Male 5 days 16.3 — 78.6 0.02 0.58 3.41 98.9
F 10 Oral, pulse b Female 5 days 28.7 — 71.0 0.02 0.19 1.55 101.5
G 10 Oral, repeat c Male C max
after 7.9 — 60.3 0.03 2.69 17.77 96.3 g
fifth dose
H 10 Oral, repeat c Female C max
after
fifth dose
19.9 — 51.6 0.04 3.27 12.65 93.0 g
From Swenson et al. (1998)
a
All rats except those in groups G and H were administered a single dose by gavage in a constant volume of 5 ml/kg bw.
b
These rats received diets containing non-radiolabelled zoxamide at a concentration of 200 ppm for 2 weeks before
receiving radiolabelled zoxamide as a single oral dose at 10 mg/kg bw.
c
These animals received five consecutive daily oral doses by gavage and were sacrificed at the C max
time-point (8 h after
dosing) on day 5 of dosing.
d
Includes urine, urine funnel wash and urine cage wash.
e
Mean total percentage of administered dose, reflects the mean and standard deviation for the individual animals.
f
No radioactivity was recovered as either 14 CO 2
or volatile organic compounds.
g
Stomach contents, stomach wash, and intestinal tract contents and wash accounted for 7.55% and 5.42% of the administered
dose for males and females, respectively.
ZOXAMIDE 487–522 JMPR 2007