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

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The excretion of radioactivity in bile, urine and faeces, and the metabolites present, were investigated
in groups of bile-duct cannulated females given a single oral dose of [carbonyl- 14 C]procymidone
(purity, > 98.5%; specific activity, 8 MBq/mg). Groups of four Sprague-Dawley rats received
[carbonyl- 14 C]procymidone at a dose of 3.5 or 62.5 mg/kg bw in corn oil; a rabbit (New Zealand
White) and a cynomolgus monkey received [carbonyl- 14 C]procymidone at a dose of 125 mg/kg bw
in 0.5% methylcellulose. Bile, urine and faeces were collected for 48 h after dosing; samples were
analysed for radioactivity and for metabolites. At termination, the gastrointestinal tract and contents
were removed and analysed for radioactivity. Metabolites were separated by TLC and identified by
co-chromatography with reference standards either before or after enzyme hydrolysis. The results are
summarized in Table 7.
Interpretation of the data from the rabbit and monkey were complicated by the high residues
in the gastrointestinal contents and carcass. Excretion of glucuronides in the urine was lower in rats
than the other two species, but with higher concentrations of acid derivatives. The indications were
that the glucuronides in rat bile are subsequently deconjugated and reabsorbed (Sugimoto, 2005d;
Mogi, 2005c, 2005d).
Table 6. Specific enzyme activities related to the metabolism of procymidone in S9 from liver of
four species
Metabolic conversion
Enzyme activity (pmol/min per mg protein)
Human Rat Monkey Rabbit
Procymidone hydroxylation 36 10 30 61
PCM-CH 2
OH oxidation 13 1 33 26
From Matsui (2005b)
PCM-CH 2
OH, hydroxyprocymidone.
S9, 9000 × g supernatant.
Table 7. Metabolite excretion profiles in bile-duct canulated females given a single dose of
[carbonyl- 14 C]procymidone
Excretion parameter
Recovery (% of administered dose)
Rat
(62.5 mg/kg bw)
Rabbit
(125 mg/kg bw)
Monkey
(125 mg/kg bw)
Faeces 0–48 h 7 3.5