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

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After each dose of [U- 14 C triazine]cyromazine (specific activity, 9.8 μCi/mg for the lowest dose
and 0.8 μCi/mg for the highest dose; radiochemical purity, 97.2%), urine and faeces were collected
at intervals over 7 days from rats in groups 2, 3, 4 and 5. Metabolite profiles in urine (collected over
0–24 h after a dose at 3 mg/kg bw and over 0–36 h after a dose at 300 mg/kg bw) and in solvent
extracts of faeces (collections over 0–72 h) were investigated by TLC and liquid chromatography
(LC). Structural assignments of resolved metabolites were confirmed by mass spectrometry. The
study was conducted according to the principles and practices of GLP (with QA certificate) and the
protocol was in accordance with OECD TG 417 (1984).
The major component present in urine was cyromazine, accounting for 72% of urinary
radioactivity (Table 12). An additional 7% was attributable to melamine, 9% to hydroxy-cyromazine
and 2% to methyl-cyromazine, although there was no detectable amount of this latter metabolite
in urine from rats at 300 mg/kg bw. Only 6% of [U- 14 C triazine]-metabolites in urine remained
uncharacterized and comprised minor metabolites, each of which represented less than 2% of urinary
radioactivity. The urinary metabolite profiles were similar between the sexes and, apart from the
absence of methyl-cyromazine in the group at the highest dose, there were no pronounced differences
between doses.
Table 12. Quantification of urinary 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
Single oral dose (pre-treated
for 14 days)
Dose (mg/kg bw)
Single oral dose
3 3 3 300
Male Female Male Female Male Female Male Female
Methyl-cyromazine 1.98 2.93 2.15 2.02 1.63 1.59 ND ND
Unidentified 5.19 6.11 6.54 6.76 6.60 6.09 2.59 1.73
Melamine 5.27 7.20 6.54 7.15 7.05 10.68 3.48 2.31
Hydroxy-cyromazine 6.76 5.69 14.02 8.47 8.32 4.06 4.94 4.86
Cyromazine 58.92 59.26 54.35 50.82 63.82 61.63 67.63 68.64
From Capps (1990)
ND, not detected.
The chromatographic profile of metabolites in faecal extracts was similar to that in urine with
71% of radioactivity corresponding to cyromazine and 7% to melamine (Table 13). An average
of 8% co-chromatographed with methyl-cyromazine and hydroxy-cyromazine and 13% did not
chromatograph with available standards and appeared to comprise several minor metabolites. The
faecal metabolite profiles were similar for male and female rats.
CYROMAZINE X-X JMPR 2006