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

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in the number of litters and fetuses with developmental variations in all treated groups. Slight
increases were noted in reduced ossification of the skull in all groups and in unossified sternebrae
(No. 5 and/or No. 6 and other sternebrae) in the groups at 100 and 300 mg/kg bw per day. These very
slight increases in the group at 100 mg/kg bw per day may have been due to random occurrence as
there were no other signs of fetal toxicity. A definite increase was noted in unossified sternebrae in
the group at 600 mg/kg bw per day.
Table 31. Incidence of skeletal variations of fetuses in a study of developmental toxicity in rats
given cyromazine by gavage
Finding
Dose (mg/kg bw per day)
0 (control) a 100 300 600
No. of. litters examined 23 22 25 24
No. of fetuses examined skeletally 224 217 238 224
Skull, reduced ossification (No. of litters affected) 0 (0) 2 (1) 1 (1) 2 (2)
Hyoid unossified (No. of litters affected) 5 (4) 3 (3) 3 (2) 0 (0)
Vertebrae, reduced ossification (No. of litters affected) 1 (1) 2 (2) 1 (1) 1 (1)
Pubis unossified (No. of litters affected) 0 (0) 0 (0) 1 (1) 0 (0)
Metetarsals unossified (No. of litters affected) 0 (0) 0 (0) 1 (1) 0 (0)
Sternebrae No. 5 and/or No. 6 unossified (No. of litters
affected)
48 (17) 63 (19) 79 (22) 171 (23)
Other sternebrae unossified (No. of litters affected) 2 (2) 5 (4) 5 (4) 24 (11)
From Rodwell (1979)
a
IRDC reported incidence of sternebrae No. 5 and/or No. 6 unossified among historical controls: 12.5% of the fetuses in
45.7% of the litters.
Cyromazine was not teratogenic in rats given doses of up to 600 mg/kg bw per day by gavage.
Signs of maternal toxicity (clinical signs of toxicity and decreased body-weight gain) were observed
at 300 and 600 mg/kg bw per day and fetal toxicity (decreased body weight and reduced ossification)
was observed in the group at the highest dose. The NOAEL for maternal toxicity was 100 mg/kg bw
per day and the NOAEL for developmental toxicity was 300 mg/kg bw per day (Rodwell, 1979).
Rabbits
Groups of 16 artificially inseminated Dutch Belted rabbits were given cyromazine (purity,
96.3%) as a single daily dose at 0, 25, 50 or 75 (experiment 1) and 0, 10, 30 or 60 mg/kg bw per day
(experiment 2) a constant volume of 1 ml/kg (in 1% (w/v) in aqueous CMC) orally by gavage on days
6–27 (inclusive) of gestation. The day of artificial insemination was designated day 0 of gestation.
Before treatment, the females were observed daily for mortality and overt changes in appearance
and behaviour. The females were observed daily for mortality and clinical signs of toxicity on days
6–28 of gestation. Dams not surviving to the scheduled sacrifice were necropsied and fetuses from
these dams were examined externally and preserved in 10% neutral buffered formalin. Any female
showing signs of abortion was sacrificed and examined for grossly evident morphological changes.
Intact fetuses were examined externally and preserved in 10% neutral buffered formalin. Individual
maternal body weights were recorded on days 0, 6, 12, 18, 24 and 28 of gestation. On day 28 of
gestation, all surviving females were killed and the uterus was excised and weighed. The number and
location of viable and non-viable fetuses, early and late resorptions, number of total implantations
and corpora lutea were recorded. The dams were examined macroscopically and maternal tissues
were preserved for microscopic examination only as deemed necessary by the gross findings. All
CYROMAZINE X-X JMPR 2006