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

356
the applied dose in receptor fluid plus unstripped epidermal membrane. Twenty-four hours after the
application of procymidone at 0.295, 1.48 or 500 g/l, absorption through rat epidermis was 79%,
45% and 0.8% of the applied radioactivity respectively. Absorption through human membranes was
lower than rat membranes: 5.3%, 4.7% and 0.022% of applied doses of 0.295, 1.48 and 500 g/l. The
study claimed GLP compliance and complied with OECD test guideline 428 (Owen, 2002).
1.2 Biotransformation
See also section on special studies.
Mice
Groups of five male ICR mice were given a single oral dose of [phenyl- 14 C]procymidone
(radiochemical purity, > 99%; specific activity 22.8 mCi/mmol (843.6 MBq/mmol) at a dose of
100 mg/kg bw in corn oil. Urine and faeces were collected over 2 days and analysed for metabolites
by TLC and comparison with standards. A range of tissues was extracted and analysed for metabolites
by TLC. The predominant metabolites in the urine were the acid derivatives of procymidone
(Table 3). Procymidone was the main component in faeces. In tissues and blood, the major component
was procymidone, with alcohol derivatives being present at higher concentrations than the acids.
(Kimura et al., 1988)
Rats
Male Sprague-Dawley rats received a single oral dose of [phenyl- 14 C]procymidone (purity, > 99%;
specific activity, 22.8 mCi/mmol (843.6 MBq/mmol) at 100 mg/kg bw in corn oil. Urine and faeces
were collected for 2 days after dosing. Tissues were removed from other groups of rats at intervals up to
72 h after dosing. Samples of excreta, blood and tissues were prepared and analysed for metabolites by
TLC and comparison with standards. The predominant metabolites in the urine were the acid derivatives
of procymidone (Table 3). Procymidone was the main component in the faeces. In tissues and blood,
the major component was procymidone, with alcohol derivatives being present at higher concentrations
than the acids. The metabolic profile in rats was similar to that in mice (Table 3) (Kimura et al., 1988).
A similar pattern of acid metabolites in excreta and alcohol derivatives in tissues was reported after the
administration of procymidone at a dose of 25 mg/kg bw (Mikami & Yamamoto, 1976).
Table 3. Metabolites in excreta from rats and mice given [phenyl- 14 C]procymidone a single dose
at 100 mg/kg bw
Metabolite a
Recovery (% of administered dose)
Mice
Rats
Urine Faeces Urine Faeces
PCM 2.6 7.0 0.2 5.2
PCM-CH 2
OH 7.1 2.1 3.2 1.1
PA-CH 2
OH 1.4 0.5 1.5 0.3
PCM-COOH 20 1.4 22 0.4
PA-COOH 39 3 47 0.6
DCA < 1 < 1 < 1 < 1
From Kimura et al. (1988)
DCA, 3,5-dichloroaniline; 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
See Figure 1 for key.
PROCYMIDONE 349–401 JMPR 2007