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

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groups in conception frequencies, mean numbers of corpora lutea, implantation site number or in the
values calculated for pre- and postimplantation losses. All differences were within the normal range
of deviation expected of rats of this strain and age.
Examination of the fetuses after dissection from the uterus showed normal and expected values
unrelated to treatment for the sex distribution, placental weight, fetal weight, external variations and,
in general, external malformations. The only external malformations observed were in two fetuses
from the group at 100 mg/kg bw per day.
Soft-tissue variations were found in all groups, the more common being unilateral or bilateral
dilated renal pelvis and ureter, but their incidence was not treatment-related. Dilated cerebral
ventricle was found in one fetus in each of the groups at 100 and 1000 mg/kg bw per day. The mean
percentages (± standard deviation) of fetuses per litter with soft tissue variations in the groups at 0,
100, 300 and 1000 mg/kg bw per day were 12.6 ± 14.1%, 17.6 ± 19.4%, 13.0 ± 14.6% and 21.1 ±
18.7%, respectively. The differences were considered to be incidental and all percentages were well
within the range for historical controls. These historical means and ranges in a database of 1594
fetuses were: dilated renal pelvis: mean, 13.6%, range, 7.6–21.6%; dilated ureter: mean, 1.4%, range,
0.5–3.6%; total soft-tissue variations: mean, 13.7%, range, 7.6–21.6%. Soft-tissue malformations
occurred in single fetuses of each group at 0 and 100 mg/kg bw per day, but none was found in the
groups at 300 or 1000 mg/kg bw per day.
Skeletal variations with or without involvement of the associated cartilaginous structures were
found in all groups. These involved the skull, ribs, sternum and limbs. The mean percentages of
affected fetuses per litter in the groups at 0, 100, 300 and 1000 mg/kg bw per day were 88.8%,
88.3%, 92.3% and 92.9%, respectively. All except one of the skeletal variations appeared to be
without any dose–response relationship. The exception was incomplete ossification of the thoracic
centra, the incidence of which showed a statistically significant increase (Wilcoxon one-sided test)
at 1000 mg/ kg bw per day. In spite of this finding, it appeared to be incidental to treatment because
no associated evidence for incomplete ossification was found in other parts of the vertebral column.
The percentages (± standard deviation) of fetuses per litter with this particular variation at 0, 100,
300 and 1000 mg/kg bw were: 3.0 ± 8.2%, 3.4 ± 8.3%, 1.6 ± 5.1% and 9.2 ± 12.0%. The mean and
range for historical controls, based on two experiments carried out in 1997–1998, with updated
classification of fetal findings as malformations and variations, were 2.7% and 1.8–3.5%. Skeletal
tissue malformations in the form of malpositioned and bipartite ossification of sternebrae (with
unchanged cartilage) occurred in individual fetuses of the groups at 0, 100 and 300 mg/kg bw per
day, but none was found at 1000 mg/kg bw per day.
Thus under the conditions of this study of prenatal developmental toxicity, the oral administration
of boscalid to pregnant Wistar rats from implantation until 1 day before the expected day of parturition
(days 6–19 of gestation) evoked no overt maternal toxicity up to the limit dose of 1000 mg/kg bw per
day. Furthermore, there were also no substance-induced, dose-related influences on the gestational
parameters and no signs of boscalid-induced teratogenicity, up to and including the limit dose of
1000 mg/kg bw per day.
There were no indications for boscalid-induced teratogenicity. The NOAEL for maternal toxicity
was 1000 mg/kg bw per day, the highest dose tested. The NOAEL for developmental toxicity was
300 mg/kg bw per day on the basis of reduced ossification of thoracic centra at 1000 mg/kg bw per day
(Schilling & Hellwig, 2000b).
Rabbit
In a study of developmental toxicity, groups of 25 artificially inseminated Himalayan rabbits
were given boscalid (batch No. N 37; purity, 94.4%) at a dose of 0, 100, 300 or 1000 mg/kg bw in an
aqueous suspension (0.5% Tylose CB 30.000 in doubly distilled water) administered by stomach tube
BOSCALID X-X JMPR 2006