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

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conducted on all mice during the period before dosing and on all mice in the control group and those
at the highest dose at 6-month intervals thereafter. Haematology, consisting of differential counts and
cell morphology, was conducted on: (a) 10 males and 10 females before dosing; (b) 10 males and 10
females in the control group and at the highest dose at 52 and 78 weeks; (c) all mice in the recovery
group at week 57; and (d) all mice killed because of their moribund condition. Blood chemistry
investigations and urine analysis were also performed on: (a) 10 males and females that were not assigned
to the study before dosing; (b) 10 males and females in the control group and at the highest
dose at 52 and 78 weeks; and (c) all mice in the recovery group at week 57.
Ten males and ten females per group were killed during week 52. Ten additional mice from the
groups of females at 2500 ppm and the groups of males at 0, 2500 and 4500 ppm were placed on control
diet in weeks 53–56 and killed during week 57. The remaining surviving mice were killed during week
79 or 80. All mice that were killed were subjected to a detailed gross pathological examination. Mice that
were found dead or killed in extremis were also autopsied. Specified organs of mice killed at s cheduled
times were weighed and specified tissues were collected, fixed and examined microscopically.
Dietary analyses performed on each diet batch (prepared every 2 weeks) revealed that difenoconazole
was present at the targeted concentrations. Diet mixes were an average of 101.0%, 99.8%,
100.2%, 97.3% and 99.4% of nominal concentrations at 10, 30, 300, 2500 and 4500 ppm, r espectively.
The homogeneous distribution of difenoconazole in the diet mixes and its stability for at least 16 days
at room temperature was also determined.
Table 5. Mortality during an 18-month study in mice fed diets containing difenoconazole
Parameter
Dietary concentration (ppm)
Males
Females
0 10 30 300 2500 a 4500 0 10 30 300 2500 a 4500
No. at initiation 70 60 60 60 70 70 70 60 60 60 70 70
Died/moribund, killed. 0 0 0 0 0 3 0 0 0 0 16 52
days 1–9
Moribund, killed day 10 0 0 0 0 0 1 0 0 0 0 0 18
Re-assignment day 10 −10 +10
Died/moribund, killed. 0 0 0 0 0 7 0 0 0 0 3 0
days 11–21
Died/moribund, killed. 2 2 2 4 0 3 3 3 4 4 2 0
weeks 4–52
Interim kill, week 53 10 10 10 10 10 10 10 10 10 10 10 0
Post-recovery kill, 9 b 0 0 0 10 10 0 0 0 0 10 0
week 57
Died/moribund, killed 9 8 8 6 2 7 10 5 6 6 1 0
weeks 53–68
Died/moribund, killed 9 8 13 16 14 13 13 7 11 5 9 0
weeks 69–80
Terminal kill, weeks 31 32 27 24 34 16 24 35 29 35 29 0
79–80
Percentage survival to
termination c 62 64 54 40 68 32 48 70 58 70 36 0
From Cox et al. (1989a)
a
Received diet containing difenoconazole at 3000 ppm until day 21, when the dietary concentration was reduced to 2500 ppm.
b
One mouse in the recovery group died during recovery.
c
Excluding interim and post-recovery kills.
DIFENOCONAZOLE 201–272 JMPR 2007