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

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Seven days after an oral dose of [U- 14 C triazine]cyromazine, tissue residues were detectable only
in carcass (at 0.004–0.017 ppm after the lowest dose and 0.565–0.782 ppm after the highest dose), liver
(at 0.004–0.011 ppm after the lowest dose and 0.455–0.601 ppm after the highest dose) and erythrocytes
(at < 0.001–0.001 ppm after the lowest dose and 0.153–0.164 ppm after the highest dose) of rats at
3 or 300 mg/kg bw and in the spleen (< 0.001 ppm) of female rats at 300 mg/kg bw. Tissue residue
concentrations were very low, < 0.017 ppm at 3 mg/kg bw and < 0.79 ppm at 300 mg/kg bw.
A single oral dose of [U- 14 C triazine]cyromazine at 3 mg or 300 mg/kg bw was extensively
and rapidly absorbed in male and female rats. At both doses, excretion was rapid and predominately
in the urine. Seven days after dosing, tissue residues were very low and detectable only in carcass,
liver, erythrocytes and spleen. There were no pronounced differences between the sexes and relatively
minor differences between the doses. The pretreatment of rats with unlabelled cyromazine (3 mg/kg
bw per day) for 14 days before a single radiolabelled dose of 3 mg/kg bw had no marked effect on its
absorption or excretion (Capps, 1990).
The blood kinetics, tissue distribution and tissue depletion of radioactivity were studied in
male and female Sprague-Dawley rats given [U- 14 C triazine]cyromazine as a single oral dose at
3 mg or 300 mg (specific activity, 1.87 MBq/mg for the lowest dose and 36.67–46.14 kBq/mg for the
highest dose; radiochemical purity, > 97%)/kg bw in ethanol : PEG 200 : water (2 : 5 : 3 v/v).
Table 4. Design of a study to investigate blood kinetics, tissue distribution and tissue depletion in
rats given [U- 14 C triazine]cyromazine as a single oral dose
Group Number and sex Regime
E1 Three males Approximately 3 mg/kg bw with collection of blood over a time course
E2 Three males Approximately 300 mg/kg bw with collection of blood over a time course
E3 Three females Approximately 3 mg/kg bw with collection of blood over a time course
E4 Three females Approximately 300 mg/kg bw with collection of blood over a time course
F1 Twelve males Approximately 3 mg/kg bw with collection of tissues over a time course
F2 Twelve males Approximately 300 mg/kg bw with collection of tissues over a time course
From Paul & Dunsire (1994)
Blood was collected from rats in groups E1 to E4 at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 32, 48, 72, 96
and 120 h after dosing. Based upon the profiles determined for groups E1 and E3, rats in groups F1
and F2 were killed in groups of three over a time course (F1, 0.5, 3.5, 5.5 and 24 h after dosing; F2,
8, 21, 27 and 48 h after dosing) and samples of a range of tissues were taken for the measurement
of radioactivity present. These comprised heart, lungs, spleen, liver, abdominal fat, skeletal muscle,
brain, bone, testes, kidney, urinary bladder, plasma, erythrocytes, gastrointestinal tract and contents
and residual carcass. Radioactivity was measured by LSC, either directly or after sample combustion.
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).
Blood kinetics data show that after a dose at 3 mg/kg bw, concentrations of radiolabel rose
quickly, reaching a maximum at 0.5 h after dosing (Table 5). By 8 h after dosing, blood concentrations
had declined markedly and by 24 h approached background values. Elimination appeared to be
biphasic, with an initial rapid phase of 2–12 h, followed by a slower phase. In males given a dose at
300 mg/kg bw, two peaks were present, at 0.5 and 8 h. After 24 h, [U- 14 C triazine] concentrations
declined rapidly. In female rats at 300 mg/kg bw, concentrations of the radiolabel rose to a broad
plateau between 1 h and 4 h, declining quickly after 12 h. The plasma data showed that the area
under the curve of concentration-time (AUC, 0–24 h) increased approximately 150-fold after a
100-fold increase in dose, reflecting the sustained high blood concentrations, particularly at the
CYROMAZINE X-X JMPR 2006