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

50
Table 2. Radioactivity in blood cells and plasma of rats given a single dose of [ 14 C]boscalid
(diphenyl label)
Tissue
Concentration of radioactive residues (μg eq/g tissue)
Dose (mg/kg bw)
50 500
Males Females Males Females
Time-point (h)
8 24 35 8 24 35 8 24 35 8 24 35
Blood cells 0.64 0.12 NA 0.78 0.13 NA 1.74 0.31 0.22 1.35 0.43 0.13
Plasma 1.14 0.14 NA 1.52 0.17 NA 3.52 0.40 0.09 2.84 0.51 0.17
From Leibold et al. (2000) and Leibold (2002)
NA, not available.
In rats given a single oral dose of [ 14 C]boscalid at 500 mg/kg bw, the plasma c oncentration–
time curve showed two maxima. The first plasma maximum was reached 0.5–1 h after dosing with
c oncentrations of 2.61 μg eq/g in males and 3.52 μg eq/g in females. The second plasma maximum
occurred after 8 h, when plasma concentrations were 4.46 and 3.77 μg eq/g in males and females,
respectively. At later times, plasma concentrations declined to 0.01 μg eq/g in males and 0.03 μg eq/g
in females at 120 h after dosing. The initial half life (t½) was calculated to be 8.0 h in males and
9.1 h in females. The terminal t½ was 20.2 h in males and 27.4 h in females. The area under the
concentration–time curve (AUC) was 68.4 μg eq × h/g in males and 75.5 μg eq × h/g in females.
In rats given a single oral dose of 50 mg/kg bw of [ 14 C]boscalid, the plasma concentration–time
curve also showed two maxima. The early peak was reached after 0.5 h when plasma c oncentrations
were 0.99 μg eq/g in males and 1.40 μg eq/g in females. The later peak occurred after 8 h, when
p lasma concentrations were 1.54 and 1.58 μg eq/g in males and females, respectively. After this
s econd maximum, there was a biphasic decline in plasma concentrations to 0.01 μg eq/g in both
males and females at 120 h after dosing. The initial t½ values were 7.2 h and 8.2 h in males and
females, respectively. Terminal t½ values were 41.7 and 30.1 h in male and female rats, respectively.
The AUC values were 21.2 μg eq × h/g in males and 24.4 μg eq × h/g in females. Increasing the dose
by a factor of about 10 thus resulted in an increase of the AUC values by a factor of approximately 3
in both sexes. These kinetic data are summarized in Table 3.
Table 3. Pharmacokinetic parameters of radioactivity in plasma after single
oral doses of [ 14 C]boscalid (diphenyl label)
Parameter
Dose (mg/kg bw)
50 500
Males Females Males Females
First C max
(μg eq/g) 0.99 1.40 2.61 3.52
First T max
(h) 1.0 0.5 0.5–1.0 0.5–1.0
Second C max
(μg eq/g) 1.54 1.58 4.46 3.77
Second T max
(h) 8 8 8 8
Initial t½ (h) 7.2 8.2 8.0 9.1
Terminal t½ (h) 41.7 30.1 20.2 27.4
AUC (μg eq × h/g) 21.2 24.4 68.4 75.5
From Leibold et al. (2000) and Leibold (2002)
AUC, area under the curve of concentration–time.
BOSCALID X-X JMPR 2006