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

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were reduced by 13% relative to controls, with food consumption reduced by 12% in 375 ppm males.
Relative to the control group, maternal body-weight gain was reduced by 35% at 750 ppm, and
marginally (10%) at 375 ppm during the period before mating. Body weight was not affected during
gestation, but during lactation the group at 750 ppm lost weight for days 1–4 (−7.4 g vs + 4.4 g in the
control group), days 10–14 (−12.1 g vs + 6.3 g in the control group), but weight gain was markedly
increased in this group for days 21–28 of lactation (+ 13.6 g vs −4.4 g in the control group). In the
group at 375 ppm, maternal body-weight gains were generally lower than those of the controls during
lactation, although not to a statistically significant extent. Food consumption for F 0
females followed
a similar pattern to body weight, being significantly reduced (17%) throughout the period before
mating, marginally reduced (10%) during gestation, and significantly reduced (41%) during lactation.
At 375 ppm, maternal food consumption during lactation was also significantly reduced (17%) relative
to controls. At 750 ppm, a significant number of F 0
males had soft or liquid faeces, and in maternal
animals emaciated appearance, ataxia, hypersensitivity to sound and clonic convulsions were observed
during lactation, a period during which food consumption and achieved dose were the highest (0.9, 2.9,
12, 41 and 67 mg/kg bw per day at doses of 7.5, 25, 100, 375 and 750 ppm respectively). Treatment
did not affect reproductive and developmental indices, and there was no evidence of teratogenicity
or embryotoxicity in the F 1
pups. However, at 750 ppm, 12 out of 30 dams had total litter loss before
postnatal day 28, compared with 0 of 30 in the control group. Of 331 pups born live at this dose, 150
died before day 28 (140 of 189 those remaining post-cull on day 4 post partem), compared to 2 of 285
in the control group (0 of 186 post-cull). Body weights were reduced by 10–14% in pups of the group
at 375 ppm, and by more than 50% at 750 ppm at postnatal day 21 (21 g vs 47 g in the control group).
OWing to the high mortality rate in pups of the group at 750 ppm, this group was discontinued at week
3 after weaning. No dose-related abnormalities were observed at necropsy.
After weaning, 27 of 30 of the male and 24 of 27 of the female F 1
pups from the group at
750 ppm that survived to day 1 after weaning died. Animals in this group were generally small,
ataxic, and had whole body tremors. Some were hypersensitive to sound or very weak, and a few
of the females had clonic convulsions. At necropsy, some of the 750 ppm animals had dried red
substance around the mouth, urine stained abdominal fur, small testes (expected in small male rats),
gaseous distention of the stomach, and evidence of gastric erosions. At 375 ppm, one rat of each sex
displayed hypersensitivity to sound. A significantly increased incidence of alopecia was observed at
375 ppm in males (14 out of 40 vs 2 out of 40 in the control group) and females (9 out of 23 vs 0
out of 24 in the control group) during the period before mating. The significant reductions in body
weights observed in F 1
pups at 375 and 750 ppm before weaning continued after weaning, with the
body weights of males at 375 ppm remaining approximately 10% below that of controls. However,
body-weight change was equivalent in all groups of males from day 29 after weaning onwards. In
F 1
females, body-weight gain was largely unaffected by treatment, and although the weights of the
group at 375 ppm remained consistently below those of the controls, after weaning the difference
rapidly became marginal (5–10%). Organ weights (absolute and relative to body weight) in the F 1
were largely unaffected by treatment. Relative brain weights were increased at 375 ppm by about 10%
in both sexes, considered an effect of reduced body weight. Reproductive and developmental indices
were unaffected in the F 1
parents and F 2
pups. Pup body weights in the F2 at birth and through to day
7 were not affected by treatment, but were significantly reduced at 375 ppm at postnatal days 14 and
21. There were no gross or microscopic findings in the F 1
adults or F 2
pups that were attributable to
treatment. Overall, there were no effects on reproductive performance at the doses tested (750 ppm
maximum in the first generation and 375 ppm in the second).
The NOAEL for pup development was 100 ppm, equal to 6 mg/kg bw per day, on the basis of
decreased pup weight gain and clinical signs at 375 ppm, equal to 22 mg/kg bw per day. The NOAEL
for adults was 100 ppm, equal to 6 mg/kg bw per day, on the basis of decreased body-weight gain and
reduced food consumption during the periods before mating and lactation in the F 0
, and clinical signs
in some F 1
adults at 375 ppm, equal to 22 mg/kg bw per day (Hoberman, 1991).
CYPERMETHRINS X-X JMPR 2006