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

334
Table 6. Incidence of selected fetal malformations and variations in rats exposed prenatally to
flusilazole
Study a
Dose
(mg/kg bw per day)
Fetal malformation or variation
Cleft palate Naris atresia Absent renal papilla Rudimentary
cervical rib
Total No. of fetuses (No. of litters) affected
Alvarez et al., (1984) 0 — — 1 (1) 3 (1)
4.6 — — 5 (2) —
9.0 — — 1 (1) —
26.6 — — 2 (2) 1 (1)
79.2 — — 1 (1) —
Lamontia et al., (1984a) 0 — — — —
10 — — — 1 (1)
50 — — — 13 (9)* c
250 28 (10)* b — 21 (12)* b 9 (7)* c
Lamontia et al., (1984b) 0 — — — —
0.4 — — 5 (5) —
2 — — 2 (2) —
10 — — 5 (5) —
50 — — 5 (4) 18 (8)* c
250 21 (5)* c — 4 (2) 15 (5)* c
Munley (2000) 0 — — — 3 (3)
0.5 — 1 (1) — 4 (4)
2 — — — 9 (6)
10 — — — 27 (15)* c
50 — 3 (2), 3 (3) d — 141 (22) c
—, no incidence.
a
Purity of flusilazole used in each study: Alvarez et al. (1984), 96.5%; Lamontia et al. (1984a), 95.6%; Lamontia et al.
(1984b), 95.6%; Munley (2000), 94.85%.
b
Jonckheere test of statistical significance.
c
Fischer exact test of statistical significance.
d
Incidence in each of the two groups at 50 mg/kg bw per day.
* p ≤ 0.05.
250 mg/kg bw per day, consisting of an increase in full fourteenth ribs and seventh cervical ribs and a
decrease in ossification of the first cervical centra. The LOAEL for maternal and embryo/fetotoxicity
was 2 mg/kg bw per day. No NOAEL could be identified; however, the study authors suggested that
the data supported the fact that the lowest dose tested (2 mg/kg bw per day) was near the bottom end
of the dose–response curve and was approaching a NOAEL (Schardein, 1998)
Rabbits
Four groups of 18 artificially inseminated New Zealand White female rabbits were given
flusilazole technical (purity, 96.5%; in corn oil) at a nominal dose of 0, 2, 5, or 12 mg/kg bw per
day (equal to 0, 1.9, 4.8, and 10.1 mg/kg bw per day based on analysis of dosing solutions) orally
by gavage on days 7–19 of presumed gestation (the day of insemination was designated as day 0
of gestation). On day 29 of gestation, all surviving does were killed and necropsied. Fetuses were
FLUSILAZOLE 317–347 JMPR 2007