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

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Mice
In a study of absorption, distribution and excretion, groups of five male and five female fasted
CD1 mice were treated with [U-phenyl ring 14 C]pyrimethanil (purity not reported) at a dose of
10 mg/kg bw by gavage in water containing 1% gum tragacanth. Mice were housed individually in
glass metabolism cages with food and water freely available. Urine and faeces were collected at 24,
48, 72 and 96 h after dosing. Cage washes were collected at 24 and 96 h after dosing. At the end of
the collection period, mice were killed and blood collected. Several tissues and organs were removed
and analysed for radioactivity. Carcass were weighed, homogenized and analysed. All samples were
analysed for radioactivity by LSC.
One male mouse died in first 24 h after dosing, probably due to gavage error. Total recovery of
radioactivity ranged from 91.96% to 123.03%, with an average recovery of 108.8%. Pyrimethanil was
absorbed quickly and excreted rapidly from the body, with excretion being nearly complete within
24 h. Urinary excretion in male mice was 60.5%, 2.83%, 0.96% and 0.15% of the administered dose
at 24, 48, 72 and 96 h after dosing, respectively. Urinary excretion in female mice was 66.32%, 2.44%,
0.80% and 0.21% of the administered dose at 24, 48, 72 and 96 h after dosing, respectively. Faecal excretion
in male mice was 21.00%, 1.71%, 0.67% and 0.39% of the administered dose at 24, 48, 72 and
96 h after dosing, respectively. Faecal excretion in female mice was 13.41%, 2.12%, 0.58% and 0.47%
of the administered dose at 24, 48, 72 and 96 h after dosing, respectively. Radioactivity in cage wash
at 96 h was 21.08% and 22.12% in male and female mice, respectively. Urine (urine + cage wash combined)
was the major route of excretion, containing 85.5 ± 10.4% of the administered dose in males
and 91.9 ± 21.0% in females. The remainder of the administered dose was excreted via the faeces. At
96 h after dosing, only the liver, kidney, blood and carcass contained measurable residues (0.003–0.040
mg pyrimethanil equivalent/kg) that were above the limit of d etection (H emmings, 1991b).
Dogs
In a study of absorption, distribution and excretion, groups of three male and three female
beagle dogs were given a gelatin capsule containing [U-phenyl ring 14 C]pyrimethanil (purity not reported)
at a dose of 10 mg/kg bw. Dogs were housed individually in stainless steel metabolism cages
with water freely available and were fed pelleted diet. Urine was collected at 6, 24, 48, and 72 h after
dosing and cages were washed and collected for quantification. Faeces were collected at 24, 48 and
72 h after dosing. Blood samples were taken from the jugular vein at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24,
30, 48 and 72 h after dosing and centrifuged to provide plasma. At the end of the collection period,
the dogs were killed. Several tissues and organs were removed and analysed for radioactivity. The
carcass was not examined for radioactivity. All samples were analysed for radioactivity by LSC.
Total recovery of the orally administered dose of pyrimethanil in excreta, cage wash and tissues
was 94.6% and 94.5% in male and female dogs, respectively. More than 70% of the orally administered
dose was excreted in 24 h and excretion was nearly complete in 48 h after dosing. The main
route of excretion was via the faeces, which accounted for 59.4% and 53.2% of the administered
dose in males and females, respectively, in 72 h. Urinary excretion in 72 h was 29.2 and 37.7% of the
administered in males and females, respectively. Study authors suggested that there was a strong evidence
to support biliary excretion of orally administered pyrimethanil since higher concentrations of
radioactivity were detected in the bile than in the liver or kidney at necropsy. With the exception of the
bile and gastrointestinal tract, the concentration of radioactive residues in the tissues at necropsy, 72 h
after dosing, was low with only the adrenals, liver, thyroid and male spleen containing concentrations
of radioactivity of > 0.1 mg equivalent/kg. The concentration of pyrimethanil-derived residues in the
blood and plasma of the dogs reached a maximum at 0.5–3 h after dosing. The C max
was calculated
as 3.68 ± 2.86 and 5.82 ± 0.13 mg equivalent/kg, and the elimination half-life (t ½
) was 11.6 ± 1.9 h
and 13.5 ± 2.7 h for male and female dogs, respectively. The results suggested that pharmacokinetic
parameters were comparable in male and female dogs (Reynolds & Swalwell, 1992).
PYRIMETHANIL 445–486 JMPR 2007