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

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30 and 60 mg/kg bw per day, respectively). This finding was statistically significant (p < 0.05) in
the group at the highest dose. However, most of these anomalies occurred only once and had been
observed in historical controls. The number of fetuses with anomalies at incidences that exceeded
values for historical controls included the following: two with carpal flexure at 10 mg/kg bw per day,
one with fused sternebrae and one with malformed sternebrae at 30 mg/kg bw per day and one with
internal hydrocephaly/dome-shaped head, one with skull anomalies (malformed nasals, premaxillae
and jugals), one forked thoracic rib and three with fused sternebrae at 60 mg/kg bw per day (Table 32).
A slight increase in the number of fetuses and litters with 27 presacral vertebrae and a 13th full rib was
noted in the treated groups compared with the control group.
Table 32. Incidence of malformations and variations of fetuses (litters) in a study of
developmental toxicity in rabbits given cyromazine by gavage—experiment 2
Finding
No. of fetuses affected (No. of litters affected)
Dose (mg/kg per day)
0 (control) 10 30 60 Historical
controls
Total No. examined 77 (14) 95 (15) 90 (13) 58 (10) 951 (149)
External malformations
Carpal flexure 0 (0) 2 (2) 1 (1) 0 (0) 4 (4)
Abdominal closure
0 (0) 0 (0) 0 (0) 2 (1) 2 (2)
defects—omphalocele
Soft tissue malformations
Internal hydrocephaly/ 0 (0) 1 (1) 0 (0) 1 (1) 3 (3)
dome-shaped head
Skeletal malformations
Scoliosis with/without 0 (0) 1 (1) 0 (0) 1 (1) 7 (7)
rib anomaly
Fused sternebrae 0 (0) 1 (1) 1 (1) 3 (3) 1 (1)
Malformed sternebrae 0 (0) 0 (0) 1 (1) 0 (0) 1 (1)
Variations a
Twenty-seven presacral 5.2 (14.3) 8.4 (26.7) 10.0 (38.5) 20.7 (50.0) 68 (36) b
vertebrae
Thirteenth full rib 7.8 (21.4 ) 20.0 (46.7) 21.1 (69.2) 32.8 (70.0) 97 (44) c
From Blair (1981b)
a
Percentage affected: fetuses (litters).
b
Range, 1.8–14.1 (13.3–44.4).
c
Range, 1.1–32.7 (7.7–70.0).
In conclusion, oral administration of cyromazine to pregnant Dutch Belted rabbits results
in maternal toxicity at doses ≥ 25 mg/kg bw per day as shown by maternal deaths, abortions and
decrease in body weight. In the first experiment, embryotoxicity was observed at 75 mg/kg bw per
day (decreased total implantations, increased postimplantation losses and decrease in the number
of viable fetuses), but no teratogenic effect was observed. In the second experiment, an increased
incidence of malformations at above the range for historical controls were seen; however, their
biological significance is uncertain. Factors relating their occurrence to treatment included the fact
that a majority involved the sternum, they occurred in all treatment groups and their frequency of
occurrence at 30 and 60 mg/kg bw per day exceeded values for historical controls. However, they
occurred generally as single incidences.
CYROMAZINE X-X JMPR 2006