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

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Seven doses C max
(µg equivalent/ml) — 10.1 17.3 23.8 31.6
T max
(h) — 2 8 4 4
AUC 2–24 h
(µg equivalent/h per ml) — 195 380 465 667
Fourteen doses C max
(µg equivalent/ml) — 15.1 26.9 30.0 46.9
T max
(h) — 2 2 2 2
AUC 2–24 h
(µg equivalent/h per ml) — 300 531 624 945
AUC 0-∞
(µg equivalent/h per ml) — 1287 2195 2714 4167
Radioactivity in urine (%) — 39 25 19 18
Radioactivity in faeces (%) — 55 70 72 78
Peak PCM (μg equivalent/ml) — 3.6 6.6 6.8 11.5
Peak PCM-NH-COOH
(μg equivalent/ml)
— 0.1 0.2 0.1 0.2
Peak PCM-CH 2
OH a (μg equivalent/ml) — 1.3 3.1 2.1 3.6
Peak PA-CH 2
OH (μg equivalent/ml) — 0.3 0.8 0.5 0.5
Peak PA-COOH(μg equivalent/ml) — 0.1 0.3 0.1 1.1
Peak glucuronides (μg equivalent/ml) — 0.2 1.2 0.6 3.3
From Sugimoto (2005c) and Mogi (2005b)
AUC, area under the curve of concentration–time; PA, procymidone acid; PA-CH 2
OH, hydroxyprocymidone acid;
PA-COOH, carboxyprocymidone acid; PCM, procymidone; PCM-CH 2
OH, hydroxyprocymidone; PCM-NH-COOH,
carboxyprocymidone.
a
Included PCM-COOH.
(b)
Dermal route
The dermal absorption of procymidone from a formulated product has been measured in rats
in vivo and in rat and human skin membranes in vitro.
Groups of four male Sprague-Dawley rats were given [phenyl- 14 C]procymidone (radiochemical
purity, 99.4%; specific activity, 449 μCi/mg (16.61 MBq/mg) formulated as Sumisclex SC at a
dose of 0.002, 0.02 or 0.2 mg/cm 2 given as an application to the shaved back. Rats were exposed for
0.5, 1, 2, 4, 10 and 24 h, the application site was then washed and the rats were killed and radioactivity
measured by liquid scintillation counting (LSC). An additional group of rats at each dose
was washed 10 h after application and excreta were collected until 168 h after dosing. Recoveries
of radioactivity were > 90%. Radioactivity was readily removed from the skin by washing and most
of the excreted radioactivity was eliminated in the urine. In the groups exposed for 10 h and then
killed 168 h after dosing, 1.2–2.5% of the administered dose remained in skin; this was considered
to be bound radioactivity that was unavailable for absorption, as excretion was essentially complete
at 120 h. Dermal absorption after a 10-h exposure was calculated to be 13%, 9% and 4% for dermal
exposures of 0.002 mg/cm 2 , 0.02 mg/cm 2 and 0.2 mg/cm 2 respectively. This study claimed compliance
with GLP and complied with OECD test guideline 427 (Savides, 2002).
In a study of dermal penetration in vitro, [phenyl- 14 C]procymidone (radiochemical purity,
99.4%; specific activity 449 μCi/mg), formulated as Sumisclex SC, was applied at a dose of 0.295,
1.48 or 500 g/l, corresponding to application concentrations of 0.003, 0.015 and 5 mg/cm 2 , to rat
and human epidermal membranes. Membranes were checked for integrity on the basis of electrical
resistance. Samples of receptor fluid (ethanol/water; 1 : 1) were taken at intervals up to 24 h after
application of the formulation and the membranes were then washed. Human, but not rat membranes
were stripped with tape to remove the stratum corneum. Absorption was calculated as percentage of
PROCYMIDONE 349–401 JMPR 2007