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

389
The NOAEL for maternal toxicity, fetotoxicity and teratogenicity was 1000 mg/kg bw per day,
the highest dose tested (Brooker, 1994).
Rabbits
In a preliminary, GLP-compliant study to determine appropriate doses for a study of gavage,
groups of seven mated New Zealand White rabbits were given quinoxyfen (purity, 96.2%) at a dose of
0 (control), 100, 300, 600 or 1000 mg/kg bw per day suspended in 0.5% methyl cellulose by gavage
from day 7 to day 19 of presumed gestation. Dams were killed on day 20 and the pups were delivered
by caesarean section. The liver and kidney weights, and the number of corpora lutea, implantations,
resorptions, and the number of dead or live fetuses were recorded. Fetuses were not weighed or sexed,
but were examined for gross external abnormalities.
At the start of the study, the female rabbits were aged 5–6 months and body weights ranged
from 2.4 to 4.0 kg. Analysis of all dose suspensions showed mean concentrations of quinoxyfen of
88–127%. Analysis of samples taken from three separate layers of the least and most concentrated
suspensions showed adequate homogeneity.
All females at 600 and 1000 mg/kg bw per day were killed humanely on day 15 of gestation
and data on reproductive parameters were not recorded for these two groups. The number of
pregnant dams was 5 out of 7, 4 out of 7 and 6 out of 7 at doses of 0 (control), 100 and 300 mg/kg
bw per day. At 300 mg/kg bw per day, one rabbit died and two were killed humanely. Signs of toxicity
in the two rabbits that were killed and in rabbits at the higher doses were body-weight loss, marked
inanition and reduced faecal output. The remaining rabbit at 300 mg/kg bw per day that died
spontaneously did not exhibit any prior signs of toxicity. Reduced feed consumption was observed
in animals at doses of ≥ 300 mg/kg bw per day compared with controls during the dosing period
resulting in reduced body-weight gains. There were no treatment related changes in pregnancy
rates, numbers of corpora lutea, implantations, resorptions or litter size in rabbits at 100 or 300 mg/kg
bw per day. There was a significant increase in the relative liver weight in rabbits at 300 mg/kg bw
per day.
The NOAEL for maternal toxicity was 100 mg/kg bw per day on the basis of evidence of
systemic toxicity at ≥ 300 mg/kg bw per day. There was no evidence of fetotoxicity or teratogenicity
at 300 mg/kg bw per day (Zablotny et al., 1993).
In the main, GLP-compliant study, groups of 18 mated New Zealand White rabbits were given
quinoxyfen (purity, 96.2%) at a dose of 0 (control), 20, 80 or 200 mg/kg bw per day suspended in
0.5% methyl cellulose by gavage from day 7 to day 19 of presumed gestation. Dams were killed on
day 28 and the pups were delivered by caesarean section. The liver, kidneys, gravid uterine weights,
and the number of corpora lutea, implantations, resorptions and dead and live fetuses were recorded.
Fetuses were weighed, sexed and examined for external, visceral and skeletal abnormalities. At the
start of the study, the body weights of the female rabbits ranged from 2.4 to 3.5 kg. The mean
concentration of quinoxyfen in the dosing suspensions ranged from 91% to 105% of the target
concentrations. The suspensions were homogenous.
There were no treatment-related mortalities during the study. One dam at the highest dose died
as a result of an error during gavage. Signs of toxicity observed in dams at 200 mg/kg bw per day
included decreased faecal output, soft faeces, perineal soiling, blood or urine containing blood in
cage pan and abortions. The number of pregnant dams was 15, 14, 15 and 14 at doses of 0 (control),
20, 80 and 200 mg/kg bw per day. Abortions were observed in two dams at 20 mg/kg bw per day and
in five dams at 200 mg/kg bw per day. The abortions at 20 mg/kg bw per day were considered to be
probably not treatment-related because there were no abortions at the higher dose of 80 mg/kg bw
per day and the incidence of abortion was noted to be close to the upper limit for historical controls.
Dams which aborted in the 200 mg/kg bw per day did so on days 20–27 of gestation, having shown
QUINOXYFEN X-X JMPR 2006