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

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Evaluation for acceptable daily intake
Unless otherwise stated, studies evaluated in this monograph were performed by GLP-certified
laboratories and complied with the relevant Organisation for Economic Co-operation and D evelopment
(OECD) and/or United States Environment Protection Agency (EPA) test guideline(s).
1. Biochemical aspects: absorption, distribution, and excretion
Rats
The absorption, distribution, and elimination of pyrimethanil was studied after oral dosing
with pyrimethanil radiolabelled with 14 C as shown in Figure 1.
In a toxicokinetic study, groups of five male and five female Crl:CD(SD)BR rats were given
[U-phenyl ring 14 C]pyrimethanil (purity, 98.1–98.4%) as a single oral dose at 11.8 or 800 mg/kg bw
by gavage in an aqueous solution of 1% (w/v) gum tragacanth. Treated rats were housed in Radley
all-glass metabolism cages for 96 h. Urine and faeces were collected at 24, 48, 72 and 96 h after
dosing. Cages were washed at 24 h and 96 h after dosing. At 96 h, various organs and tissues were removed
and blood was sampled and all were analysed for radioactivity. Tissues were either combusted
or solubilized. All samples were analysed for radioactivity by liquid scintillation counting (LSC).
Pyrimethanil was rapidly excreted in both groups, with more than 95% of the lower dose and
63–67% of the higher dose being excreted in the first 24 h (Table 1). The major route of excretion was
in the urine that, together with the cage wash, accounted for about 80% of the administered dose in
both groups, indicating at least 80% of the orally administered dose was absorbed in 96 h. There were
no sex-related differences in the route or rate of elimination in the two dosed groups.
At the lower dose, most of the tissues examined had radioactive residues that were below the
limit of detection at 96 h, except the carcass and the liver (0.082–0.223 mg pyrimethanil equivalent/
kg). At the higher dose, the highest residues were found in the liver (10.33–11.27 mg pyrimethanil
equivalent/kg) and kidneys (8.845–8.566 mg pyrimethanil equivalent/kg). The concentrations of
residue in the bone, brain, eyes, muscle, pituitary, plasma, renal fat and gonads were less than 1 mg
pyrimethanil equivalent/kg. There were no significant differences between the residue concentrations
seen in the tissues of male and female rats. There were no significant sex-related differences in the rate,
route or tissue distribution were observed in male and female rats (Needham & Hemmings, 1991).
In a kinetic study in plasma, two groups of 24 male Crl:CD(SD)BR rats were dosed orally with
an aqueous suspension of [U-phenyl ring 14 C]pyrimethanil (purity, 100%)at a nominal dose of 10 or
1000 mg/kg bw by gavage. The actual achieved doses were 9.99 and 748 mg/kg bw for the lower and
higher dose, respectively. Groups of three rats were killed at 20 min, 1 h, 1.5 h, 3 h, 5 h, 7 h, 12 h and
Figure 1. Position of the pyrimethanil radiolabel used in pharmacokinetic studies in rats
* Position of radiolabel.
PYRIMETHANIL 445–486 JMPR 2007