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

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t estes weights in the males at 2500 ppm could be attributed to the significantly lower carcass weights,
because the absolute weights were essentially equal among the groups. No treatment-related microscopic
changes were observed in the reproductive organs or in gross lesions from F0 males and females
of the control group and group at 2500 ppm and the few rats at 25 and 250 ppm with macroscopic
findings. Tissue masses in one male at 0 ppm and one at 2500 ppm were found to be spermatic granulomas.
A tissue mass in a female at 2500 ppm was diagnosed as an adenocarcinoma. Changes seen
microscopically for which no evidence was noted at autopsy included pituitary cysts or congestion in 5
of the males at 0 ppm, 4 of the females at 0 ppm and 1 female at 2500 ppm, hydrometria and lipofuscin
pigment in the uterus in 7 of the females at 0 ppm and 13 of the females at 2500 ppm and lipofuscin pigment
in the uterus ligament in 17 of the group of females at 0 ppm and 15 of those at 2500 ppm. These
findings were not unusual for rats of this strain and age and were not present in a dose-related pattern.
There were no treatment-related differences among the groups in the number of rats mating (0
ppm, 29 out of 30; 2500 ppm, 30 out of 30), the number of females becoming pregnant (0 ppm, 26 out
of 30; 2500 ppm, 30 out of 30) or on the mean pre-coital time (0 ppm, 2.5 days; 2500 ppm, 2.9 days).
Only two males (one in the control group and one at 25 ppm) failed to mate. The mean duration of
gestation was approximately 23 days in all groups. A total of 26, 25, 29 and 29 females in the groups
at 0, 25, 250 and 2500 ppm, respectively, were pregnant and gave birth to live young.
There were no differences in litter size among the groups at birth, the percentage of the pups
born alive, or sex ratios (Table 11)
There was a slight, incidental decrease in survival from days 0 to 4 among the male pups at
2500 ppm and lower body weights among the male and female pups at 2500 ppm. Body weights of
Table 11. Litter data for the F 1
generation rats in a multigeneration study of difenoconazole
Parameter
Dietary concentration (ppm)
0 25 250 2500
No. of litters 26 25 29 29
Total pups born 346 342 389 365
Total stillbirths (pups/litters) 5/5 9/6 11/7 4/2
Mean litter size day 0 (live births) 13.12 13.32 13.03 12.45
Live birth index a 98.6 97.4 97.2 98.9
Sex ratio (% males, day 0) 51.3 48.6 50.5 47.6
Males Females Males Females Males Females Males Females
Viability index (day 0–4) b 98.7 97.6 100.0 98.2 99.6 98.8 95.2# 95.3
Viability index (day 4–21) c 99.0 100.0 98.2 100.0 100.0 99.1 97.3 100.0
Mean pup weight:
Day 0 6.58 6.15 6.71 6.46 6.35 6.06 6.20* 5.82
Day 4, pre-cull 10.00 9.38 9.83 9.55 9.46 9.11 8.71* 8.33*
Day 4, post-cull 10.07 9.42 9.84 9.60 9.52 9.10 8.71* 8.37*
Day 7 16.54 15.43 16.30 15.68 15.48 14.73 12.81* 12.28*
Day 14 32.49 30.67 32.07 31.30 30.93 29.82 23.56* 22.65*
Day 21 52.44 49.00 51.54 49.45 48.82* 46.76 36.85* 35.00*
From Giknis (1988)
a
Percent of total pups born which were alive
b
Percentage of live-born pups that survived until day 4
c
Percentage of post-cull pups (day 4) that survived until day 21
# p ≤ 0.05, Mantel test for trend; * p ≤ 0.05, Healy analysis (weighted for variation in litter size).
DIFENOCONAZOLE 201–272 JMPR 2007