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

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Rats
In a GLP-compliant study, groups of five male and five female Fischer 344 rats were given
diets containing quinoxyfen (purity, 97.6%) at variable concentrations, to give target doses of
0 (controls), 250, 500 or 1000 mg/kg bw per day for 4 weeks. The rats were observed for in-life
effects and parameters including haematology, clinical chemistry, urine analysis, organ weights,
gross and microscopic examinations of organs and tissues. The histopathological examinations
were limited to the liver, kidneys and testes. At the start of treatment, the body weight of male rats
was 113.2–129.5 g and that of female rats was 105.7–121.4 g. The achieved compound intakes
were 272, 549 and 1061 mg/kg bw per day in males and 267, 531 and 977 mg/kg bw per day in
females.
No mortalities occurred during the study period. There were no overt signs of toxicity.
A dose-related reduction in food consumption was observed at all doses when compared with
controls. Although the lower feed consumption in rats treated with quinoxyfen was reported by
the investigating laboratory to be indicative of the unpalatability of the diet, it is noted that
the target doses were achieved. Body-weight gains were statistically significantly reduced at all
doses. The terminal body weights were 89%, 83% and 67% of the control values in males and
93%, 89% and 84% of the control values in females at doses of 250, 500 and 1000 mg/kg bw per
day, respectively. Clinical chemistry, urine analysis and haematology investigations did not reveal
any significant treatment-related changes; only a reduction in plasma concentrations of glucose
occurred. Statistically significant changes in organ weights were considered to be probably related
to the differences in body weight and, in the absence of any histopathological changes, of limited
toxicological significance. Gross examination at necropsy revealed small bilaterally atrophic
testes in rats in the group at 1000 mg/kg bw per day (three out of five male rats). Histopathology
revealed a moderate to severe decrease in spermatogenesis of the seminiferous epithelium in the
testes of four out of five rats. The changes in the morphology of the testes that was associated with
reduced testicular weight were noted by the study investigator to be probably related to the body
weight changes. These findings in the testes were notably not observed in subsequent studies in
rats given lower doses.
A NOAEL could not be determined due to reductions in food consumption and body-weight
gain (7–11%) at the lowest dose tested, 250 mg/kg bw per day (Szabo & Davis, 1992).
In a GLP compliant study, groups of 10 male and 10 female Fischer 344 rats were given diets
containing quinoxyfen (purity, 98.7%) at a dose of 0 (control), 10, 100 or 250 mg/kg bw per day
for 13 weeks. All animals were killed at the end of the treatment period and underwent necropsy.
Additional satellite groups of 10 male and 10 female rats were fed doses of 0 or 250 mg/kg bw
per day for 13 weeks and then kept on a quinoxyfen-free diet for an additional 4 weeks in order
to investigate recovery from any effects. The achieved daily intakes of quinoxyfen were 10, 102
and 253 mg/kg bw per day) in males and 10, 100 and 249 mg/kg bw per day in females at nominal
doses of 10, 100 and 250 mg/kg bw per day, respectively. The parameters investigated included
in-life observations, a battery of functional tests, haematology, clinical chemistry, urine analysis,
organ weights, gross and histopathological examinations of organs and tissues. Histopathology
was limited to the adrenal glands, kidneys, liver, lungs, testes and gross lesions for the groups
at 10 and 100 mg/kg bw per day. At the start of the study, the body weights of male rats ranged
from 150.1 to 185.8 g (group means, 170.6–171.4 g) and that of female rats 120.5–141.4 g (group
means, 131.8–134.3 g).
No mortalities occurred during the study period. There were no signs of treatment-related
effects during regular observations and during the battery of functional tests on day 83. The changes
in body-weight gain in males (overall body-weight gain was only 3–6% lower than that of controls
QUINOXYFEN X-X JMPR 2006