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

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fetuses were removed, weighed and examined for external malformations. Each fetus was dissected,
internally sexed and examined for visceral abnormalities and then processed for subsequent skeletal
examination. The study was conducted according to the principles and practices of GLP (with QA
certificate) and was performed before OECD TG 414 (1981) had been enacted but complied to a
great extent, except that food consumption was not measured.
Four, two, two and one animals died in the groups at 75, 60, 50 and 25 mg/kg bw per day,
respectively. There were no mortalities in the groups at 10 or 30 mg/kg bw per day or in the controls.
Nine females aborted (before death or where sacrificed) between day 20 and day 27 of gestation (two
each in the groups at 30, 50 and 60 mg/kg bw per day and three in the group at 75 mg/kg bw per
day). In experiment 2, a reduction in the amount of faeces was seen in the treated groups at various
intervals during the treatment period. This finding occurred for a longer duration with increasing
dose. Macroscopic examination of the dams post mortem revealed heart failure as a cause of death
for two females, one each in the groups at 25 and 75 mg/kg bw per day; lung congestion and oedema
were cited as possible causes of death for two females in the group at 60 mg/kg bw per day and
pneumonitis-pleuritis was determined a cause of death for one dam at 75 mg/kg bw per day. There
were no treatment-related trends in necropsy findings in either experiment when compared with those
for the respective control groups.
In experiment 1, mean maternal body-weight losses were observed primarily during days 6 to 12
of gestation at 25 mg/kg bw per day (–101 g) and days 6 to 18 at 50 (–261 g) and 75 (–399 g) mg/ kg bw
per day when compared with the control groups. This resulted in mean maternal body-weight losses
over the entire treatment period in these three groups. In experiment 2, there were moderate bodyweight
losses during days 6 to 18 of gestation in the groups at 30 (–133 g) and 60 (–255 g) mg/kg bw
per day, resulting in a slight decrease in mean maternal body-weight gain at 30 mg/kg bw per day and
a slight loss in mean maternal body weight at 60 mg/kg bw per day, for the entire study period. There
was no effect on body-weight gain at 10 mg/kg bw per day.
In experiment 1, the pregnancy rates in all groups, including controls, were considerably
reduced (12, 9, 10 and 10 females in the groups at 0, 25, 50 and 75 mg/kg bw per day, respectively)
when compared with values for historical controls (82%) for this strain of rabbit (which may have
resulted from a technician error when inseminating).
In experiment 1, there were no effects on the mean number of corpora lutea or mean fetal body
weight in the groups at 25, 50 or 75 mg/kg bw per day or on mean postimplantation loss and fetal sex
distribution in the groups at 25 or 50 mg/kg bw per day. A slight decrease in the mean number of total
implantations (19.4%) and an increase in mean postimplantation loss (400%) with a corresponding
and statistically significant decrease in the mean number of viable fetuses (50.8%) was observed
at 75 mg/kg bw per day. Malformations were not observed in the 11 litters examined in the control
group or in the eight litters examined in the group at 50 mg/kg bw per day. The only malformations
observed were fused sternebrae in one fetus from one litter (of eight litters examined) in the group
at 25 mg/kg bw per day and fetal anasarca in two fetuses from one litter (of four litters examined) in
the group at 75 mg/kg bw per day.
In experiment 2, there were no biologically meaningful or statistically significant differences in
the mean numbers of corpora lutea, total implantations, postimplantation loss, viable fetuses or the
total sex distribution in any of the treated groups when compared with the control group. Although the
mean fetal body weight was slightly reduced in all groups, this finding was considered to be unrelated
to treatment since there was both a wide deviation within each group and a slight increase in the
number of viable fetuses in the treated groups. Although there were no malformations observed in the
control group in this experiment, the genetic and developmental variations seen in the treated groups
were comparable to those cited for historical controls. In only one out of 11 recently documented
studies were no malformations observed in the controls. Anomalies were observed in all the treated
groups (5.3%, 6.7% and 12.1% of fetuses and 33.3%, 30.8% and 40.0% of litters affected at 10,
CYROMAZINE X-X JMPR 2006