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

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continued to be lower than those of the females in the control group during gestation and lactation;
body-weight gain of the females at 2500 ppm was also lower during the first week of gestation and
body-weight losses during the last week of lactation were smaller.
Food consumption by males and females at 2500 ppm was significantly lower than that of rats in
the control group throughout the pre-mating phase, approximately 11% for the males and 17% for the
females. During gestation, the females at 2500 ppm continued to consume about 17% less feed than did
the females in the control group. Food consumption by the females at 250 ppm was significantly lower
than that of females in the control group during the second week of gestation, but this difference was
c onsidered to be incidental. Food consumption by rats at 25 and 250 ppm was not affected by treatment.
Absolute weights of testes and ovary were not different among the groups. As observed in the
F 0
generation, differences in relative weights of these organs between rats at 0 ppm and 2500 ppm
were attributed to reduced carcass weights at 2500 ppm rather than specific toxic effects.
No treatment-related changes were observed at autopsy of the F 1
parental rats. Minor changes
in the epididymides, seminal vesicles and/or testis were seen in two males in the control group, two
males at 25 ppm, two at 250 ppm and five at 2500 ppm but none of these was considered to be related
to treatment. There were macroscopic findings in two females in the control group (mammary mass
and ovarian cyst), a female at 25 ppm that was found dead (fluid contents in lungs), two females at
250 ppm (uterine dilation and cyst) and one of the females at 2500 ppm that was found dead (reddish
kidney and enlarged, reddish adrenals). These findings were not considered to be unusual for rats of
this strain and were considered to be incidental to treatment.
Table 13. Litter data for the F 2
generation in a multigeneration studying rats fed diets containing
difenoconazole
Parameter
Dietary concentration (ppm)
0 25 250 2500
No. of litters 19 25 21 23
Total pups born 234 254 297 281
Total stillbirths (pups/litters) 5 / 5 30 / 9 9 / 6 29 / 9
Mean litter size day 0
(live births)
12.05 8.96 13.71 11.39
Live birth index a 97.9 88.2 97.0 93.2
Sex ratio (% males day 0) 44.1 56.3 47.9 51.9
Males Females Males Females Males Females Males Females
Viability index (days 0–4) b 98.3 94.2 91.4 96.0 97.4 100.0 93.8 93.9
Viability index (days 4–21) c 98.6 98.6 100.0 98.8 90.5 89.3 95.5 95.5
Mean pup weight:
Day 0 6.61 6.25 6.77 6.46 6.42 6.15 6.07* 5.79*
Day 4 pre-cull 9.99 9.47 10.23 9.70 9.58 9.29 8.58* 8.23*
Day 4 post-cull 10.07 9.51 10.22 9.71 9.57 9.36 8.61* 8.19*
Day 7 16.07 15.21 15.66 15.12 15.46 15.06 12.77* 12.18*
Day 14 31.76 30.34 30.75 30.15 30.80 30.02 23.45* 22.58*
Day 21 50.99 48.35 50.11 49.02 52.00 50.63 34.22* 32.99*
From Giknis (1988)
a
Percentage of total pups born that were born alive.
b
Percentage of live-born pups that survived until day 4.
c
Percentage of pups remaining after cull (day 4) that survived until day 21.
* p ≤ 0.05, Healy analysis (weighted for variation in litter size).
DIFENOCONAZOLE 201–272 JMPR 2007