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

234
after an exposure period of at least 10 weeks. The ensuing F 2
litters were reared to weaning. The diets
containing difenoconazole were fed continuously throughout the study.
There were no adverse effects of difenoconazole on survival in the parental groups of the F 0
or the
F 1
generation and there was no evidence of treatment-related clinical changes. Compared with the males
at 0 ppm, mean body weights of F 0
males in the group at 2500 ppm were significantly lower throughout the
treatment period (Table 10), beginning with significantly reduced body-weight gains during the first study
week and continuing significantly lower during most study weeks. Their body weights were approximately
8% lower by the end of the pre-mating phase and continued at about that level until they were killed.
Mean body weights of the F 0
females at 2500 ppm were significantly lower than those of the females at 0
ppm throughout pre-mating, gestation and lactation. While the body-weight gains of the females at 2500
ppm were significantly lower than those of the females at 0 ppm during pre-mating weeks 1, 3, 7, 8 and 11,
during gestation and lactation, the deficits were relatively small. Body weights of the groups of females
at 25 ppm and 250 ppm were not affected by treatment. Food consumption by rats of both sexes at 2500
ppm was consistently lower than that of rats in the control group throughout the pre-mating period. For
males, the difference was statistically significant at every pre-mating week and was an average of about
9% lower. For females, the difference was statistically significant in every pre-mating week except weeks
2 and 3 and averaged about 12% lower. Food consumption by the group of females at 2500 ppm was also
lower (about 16%) than that of the group of females at 0 ppm during the first 2 weeks of gestation. Food
consumption by the males and females at 25 and 250 ppm was not affected by treatment.
No treatment-related changes were observed at autopsy of the F 0
parental rats. There were no
differences in absolute organ weights between treated and control rats. Significantly increased relative
Table 10. Body-weight development of F 0
rats in a multigeneration study of difenoconazole
Time-point/phase
Study
day(s)
Dietary concentration (ppm)
Males
Females
0 25 250 2500 0 25 250 2500
Body weight (g)
Start of treatment 0 175.3 175.6 176.7 178.7 144.3 145.3 143.8 146.4
7 233.1 230.0 233.1 222.8* 173.4 173.4 171.6 166.0*
42 437.3 435.2 435.0 402.7* 259.2 255.5 255.7 232.2*
End of pre-mating 77 542.6 540.7 549.7 500.7* 303.9 295.2 297.0 258.3*
Beginning of gestation a 79/98 — — — — 297.9 295.7 298.6 260.1*
End of mating 98 568.7 567.7 577.9 520.2* — — — —
End of gestation a 101/118 — — — — 430.6 427.3 422.3 379.7*
Beginning of lactation a 102/119 — — — — 337.6 335.4 336.5 294.3*
End of lactation a 123/140 — — — — 346.5 342.7 341.4 300.8*
Termination 141 610.5 614.3 618.1 554.4* 324.7 317.4 313.6 284.6*
Body-weight change (g)
Premating 0–77 367.3 365.1 373.0 322.0*
Gestation
Approx. — — — — 132.7 131.6 123.7 119.6
79–118
Lactation
Approx. — — — — 8.9 7.3 4.9 6.6
102–140
Full duration 0–141 434.9 438.6 441.4 345.7* — — — —
From Giknis (1988)
a
Days variable based on when each dam started/ended the phase.
* p ≤ 0.05, ANOVA + Dunnett test.
DIFENOCONAZOLE 201–272 JMPR 2007