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

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Table 3. Half-life of pyrimethanil and its metabolites in selected tissues of rats given r adiolabelled
pyrimethanil as a single dose by gavage
Tissue
Half-life (h)
Higher dose (10 mg/kg bw)
Lower dose (800 mg/kg bw)
Males Females Males Females
Blood 10.18 7.51 18.37 22.49
Kidney 5.57 4.79 10.33 14.02
Liver 7.76 8.64 19.60 21.26
Plasma 5.41 5.23 8.22 11.69
Renal fat 3.89 3.70 10.42 20.94
From Whitby (1995a, 1995b) and Jardinet (2006)
days of exposure, the autoradiograms were developed and analysed using the Seescan Solitaire Plus
Q uantitative Whole-body Autography System (QWBAS).
With the exception of the gonads, the distribution of radioactivity was similar in male and female
rats given a single oral dose of pyrimethanil at 10 mg/kg bw. Absorption was rapid, with maximum concentrations
of radioactivity in most tissues being found at the first time-point (45 min after dosing) when
concentrations of > 10 mg equivalent/kg were present in the lachrymal glands, Harderian gland (females),
kidney, liver and white fat. Residue concentrations were > 1 mg equivalent/kg tissue in all other
tissues except for the bone and eye in males. The residues were rapidly cleared from the tissues and, by
6 h after dosing, concentrations of > 1 mg equivalent/kg were detected only in the kidney and liver (the
organs of excretion), and the white fat of females. After administration of a single oral dose of radiolabelled
pyrimethanil at 800 mg/kg bw, the peak concentrations of radioactivity in the tissues occurred
at 3–6 h in males and 6–12 h in females. Maximum concentrations of > 100 mg equivalent/kg were
detected in the adrenal gland, brown fat, Harderian gland, lachrymal glands, kidney, liver, spleen and
white fat of males and females, in the seminal vesicles of males, and in the blood, lung, lymph nodes,
myocardium, ovary, pancreas and salivary gland of females. As with the lower dose, the concentrations
fell rapidly by 24 h after dosing. The concentrations of the residues at this time were higher in females
(in which the adrenal, kidney, liver, ovary and pancreas contained concentrations of greater than 50 mg
equivalent/kg) than in the males (only the liver, kidney and thyroid contained residues at a concentration
of >10 mg equivalent/kg). Absorption was more protracted at the higher dose, and the concentration of
residues in the blood and highly perfused tissues did not increase in a dose-related manner. It is therefore
possible that the absorption of pyrimethanil was limited by the dissolution rate of the compound.
Irrespective of the dose, the radioactive residues were rapidly cleared from all rats such that by 48 h after
dosing there was virtually no quantifiable radioactivity in any of the tissues (Whitby, 1993).
Groups of three male Crl:CD(SD)BR rats were given [U-phenyl ring 14 C]pyrimethanil (purity, > 98%)
at a dose of 10 mg/kg bw orally once per day for 28 days, with periodic sacrifices at days 1, 3, 5, 8, 11, 17,
23, and 28. An additional group of rats was placed in all-glass metabolism cages after the final dose on day
28 for collection of urine and faeces for 4 days. At necropsy, various tissues and organs were removed and
analysed for radioactivity. Plasma was prepared from blood and analysed. Tissues were either combusted or
solubilized. All samples were analysed for radioactivity by LSC.
Recovery of radioactivity was not reported. Detectable concentrations of radiolabel were found
in the adrenals, blood, kidney, liver, spleen, and thyroid after exposure. At 24 h, after a single dose,
only the blood (0.16 mg/kg bw) and liver (0.40 mg/kg bw) displayed detectable concentrations of
radiolabel that were higher than the limit of detection. Four days after the last dose, detectable concentrations
of radiolabel were found only in the liver, kidney, and thyroids. It appeared that the
concentrations in the blood, kidney, and thyroid would continue to increase with increased exposure
PYRIMETHANIL 445–486 JMPR 2007