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

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0.7 ± 3.5%, 1.8 ± 4.2%, 2.9 ± 9.0% and 8.3 ± 17.2%. 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 0.1% and 0.0–0.5%, respectively.
Skeletal tissue malformations (the most common being defect of the cardiac muscular
ventricular septum) occurred in individual fetuses in the groups at 0, 100 and 300 mg/kg bw per day,
but none was found at 1000 mg/kg bw per day.
There were no indications that boscalid induced teratogenicity. The NOAEL for maternal
toxicity was 300 mg/kg bw per day on the basis of reduced feed consumption and body-weight gain
at 1000 mg/kg bw per day. 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.
The Meeting concluded that boscalid is unlikely to be teratogenic to man (Schilling & Hellwig,
2000a).
2.6 Special studies
(a)
Neurotoxicity
(i) Neurotoxic potential
In a single-dose study of neurotoxicity, groups of 10 male and 10 female Wistar rats were given
boscalid (batch No. N 46; purity, 96.3%) as a single oral dose at 0, 500, 1000 or 2000 mg/ kg bw by
gavage. The vehicle was a 0.5% aqueous solution of Tylose CB 30.000, and the dose administration
volume was 20 ml/kg bw.
The rats were observed for up to 2 weeks after dosing. Their general state of health was examined
and recorded daily. Body weight was determined 7 days before dosing, on day 0 (administration of
test substance) and on days 7 and 14. Functional observational batteries (FOB) and motor activity
measurements were carried out on all rats on the same days. The measurements for day 0 were made
within a few hours after dosing. Five rats per sex and dose were killed, fixed by in-situ perfusion and
subjected to neuropathological examinations. The remaining animals were killed with CO 2
under
anaesthesia without any further examinations. The stability, homogeneity and correctness of the
concentrations of the boscalid preparation were verified analytically.
There were no deaths during the study and the only clinical sign of toxicity that was treatmentrelated
was piloerection in two female rats at 2000 mg/kg bw during the FOB on day 0. There were no
other test-substance related effects at any dose. In particular, no signs of neurotoxicity were observed.
The NOAEL for neurotoxicity after a single oral dose of boscalid was 2000 mg/kg bw in male and
female rats (Mellert et al., 2000d).
In a multiple-dose study of neurotoxicity, groups of 10 male and 10 female Wistar rats were
given diets containing boscalid (batch No. N 46; purity, 96.3%) at a concentration of 0, 150, 1500
or 15 000 ppm, equal to 0, 10.5, 103 and 1050 mg/kg bw per day in males and 0, 12.7, 124.5 and
1273 mg/kg bw per day in females, for 3 months.
Food and water consumption were determined once per week. Body weight was determined
once per week and on the days when FOB were performed. A check of the general state of
health was made at least daily. Furthermore, the rats were thoroughly examined and palpated
once per week. FOB and measurements of motor activity were carried out in all animals 7 days
before the start of the administration and on days 22, 50 and 85. Five rats per sex and dose
were killed, then fixed by in-situ perfusion and subjected to neuropathological examinations. The
remaining animals were killed with CO 2
under anaesthesia without any further examinations. The
BOSCALID X-X JMPR 2006