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

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To evaluate the potential (noted above) for a dominant lethal effect, a second experiment was
performed. Groups of 12 male mice (the control group consisted of 36 mice) were given cypermethrin
(dissolved in DMSO) as five daily oral doses at 0, 2.5, 5.0, 7.5 or 10 mg/kg bw. After dosing, each
male was mated with three virgin females for 4 days and subsequently provided with virgin females
every 4 days for 3 weeks. Female mice were examined for evidence of dominant lethality 13 days
after mating. In addition, 40 males of proven fertility were treated for five successive days at the same
doses, 0, 2.5, 5.0, 7.5 and 10 mg/kg bw. These animals were also mated with four virgin females
on four successive days for 3 weeks. Four animals from each group were sacrificed for histological
examination of the testes and epididymis on days 1 and 7 after last dose. In contrast to the previous
trial, no reduction in fetal implants was noted in any of the animals mated with cypermethrin-treated
males. The number of early fetal deaths was marginally increased at the highest dose in the 12–16
days after dosing and in the first 4 days after treatment with 7.5 mg/kg bw in males. In the groups
of animals examined histologically, no abnormalities were detected in the testes and epididymis and
there were no observable histological differences between any of the test groups and the controls
(Annex 1, reference 33; Dean et al., 1977).
(c)
Developmental toxicity
Rats
Groups of 25 pregnant female Sprague-Dawley rats were given cypermethrin at a dose of
0, 17.5, 35 or 70 mg/kg bw per day by gavage in corn oil during days 6 to 15 of gestation. The
females were sacrificed on day 21 of gestation for examination of uterine contents, and fetuses were
given a gross examination, including skeletal and somatic examinations. One female at 70 mg/kg
bw per day was found dead and one female at 70 mg/kg bw per day was killed for ethical reasons
following severe convulsions. Eleven out of 25 females in the group at 70 mg/kg bw per day showed
neurological disturbances (ataxia, convulsions, hypersensitivity to noise). A dose-related reduction
in maternal body-weight gain was observed in the groups at 35 and 70 mg/kg bw per day. There were
no indications of any embryotoxic or teratogenic effects.
The NOAEL for maternal toxicity was 17.5 mg/kg bw per day on the basis of reduced bodyweight
gain at 35 mg/kg bw per day and higher. The NOAEL for developmental toxicity was
70 mg/ kg bw per day on the basis of the absence of fetal effects at the highest dose tested (Annex 1,
reference 33; Tesh et al., 1978).
Rabbits
Groups of 20 pregnant rabbits (30 rabbits were used as an additional control group) were
given cypermethrin at an oral dose of 0, 3, 10 or 30 mg/kg bw dissolved in corn oil by gavage from
day 6 to day 18 of gestation. On day 28 of gestation, the rabbits were sacrificed and examination
made of live fetuses, dead fetuses, resorption sites and corpora lutea. Live fetuses were maintained
for 24 h to assess viability. Fetuses were also examined for gross somatic and skeletal deformities.
There was no significant mortality or differences in weight gain during gestation. There were no
significant differences between control and test groups with respect to pregnancy, fetal death or
survival. Although a wide range of skeletal and visceral abnormalities were found in the course of the
study, there were no differences between control and test groups with respect to abnormalities.
The NOAEL for maternal and developmental toxicity was 30 mg/kg bw per day as there were
no treatment-related effects at the highest dose tested (Annex 1, reference 33; Dix, 1978).
Groups of 20 mated New Zealand White rabbits were given cypermethrin technical (purity,
95.7%) at a daily dose of 0, 100, 450 or 700 mg/kg bw per day as a 50% concentration in corn oil
CYPERMETHRINS X-X JMPR 2006