Pesticide residues in food — 2006: Toxicological ... - ipcs inchem

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Table 13. Quantification of faecal metabolites in rats given a single oral dose of [U- 14 C triazine]
cyromazine at 3 or 300 mg/kg bw
Metabolite
Percentage of administered radioactivity
Group 2 Group 3 Group 4 Group 5
Single intravenous
dose
Single oral dose
Dose (mg/kg bw)
Single oral dose
(pre-treated for 14 days)
Single oral dose
3 3 3 300
Male Female Male Female Male Female Male Female
Unidentified 0.34 0.22 0.34 0.70 0.27 0.50 0.33 0.25
Melamine 0.38 0.51 0.47 0.16 0.22 0.15 0.33 0.32
Metabolite
mixture a 0.38 0.50 0.92 0.21 0.20 0.13 0.43 0.24
Unidentified 0.13 0.10 IS IS 0.12 IS 0.50 0.40
Unidentified IS IS IS IS IS IS 0.09 0.14
Cyromazine 3.77 4.84 2.78 2.59 2.26 1.83 5.76 4.95
Unidentified 0.14 0.19 0.04 0.06 0.12 0.07 0.07 0.05
Unidentified 0.04 0.08 < 0.01 0.04 0.11 0.02 < 0.01 < 0.01
From Capps (1990)
IS, Metabolite zones incompletely separated for samples from rats at the lowest dose, compared with those at the
highest dose.
a
Mixture of hydroxy-cyromazine, methyl-cyromazine and minor metabolites.
The predominant metabolic pathway for cyromazine in the rat involves biotransformation to
hydroxy-cyromazine and methyl-cyromazine and then to melamine as illustrated in Figure 2.
In male and females rats given a single oral dose of [U- 14 C triazine]cyromazine at 3 mg
or 300 mg/kg bw, the absorbed dose was incompletely metabolized, with cyromazine being
the predominant component of both urine and faeces. Cyromazine was metabolized to methylcyromazine,
hydroxy-cyromazine and melamine. There were no pronounced differences between
the sexes and relatively minor differences between the doses. The dosing of rats with unlabelled
cyromazine at a dose of 3 mg/kg bw per day for 14 days before a single radiolabelled dose at
3 mg/kg bw had no marked effect on its biotransformation (Capps, 1990).
Monkeys
In a study performed to determine the excretion pattern of cyromazine in monkeys, metabolism
was also investigated. Two male and two female Macaca fasicicula monkeys were given a single
oral dose of [U- 14 C triazine]-cyromazine at 0.05 mg/kg bw. An additional two male and two female
monkeys were given a single oral dose of [U- 14 C triazine]cyromazine at 0.5 mg/kg bw. The doses
were administered in capsules. Each monkey was housed in a metabolism cage to which it had
previously been acclimatized. Urine and faeces were collected for 24 h before dosing and at each
day after dosing for 4 days. Radioactivity in urine and in combusted samples of faeces was measured
by LSC. Aliquots of urine collected over the first 24 h after dosing were analysed by TLC against
cyromazine and melamine reference standards. The study was not performed according to GLP, but
it was an investigative study designed to complement the regulatory submission on metabolism. The
study was regarded as additional information for the evaluation.
In all day-1 urine samples, more than 93% of the radioactivity present was characterized as
cyromazine and the remainder as melamine (Table 14). There was considered to be no difference in
metabolism between the doses or between the sexes.
CYROMAZINE X-X JMPR 2006