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

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In a GLP-compliant study to determine palatability and potential toxicity, one male and one
female beagle dog were given diets containing quinoxyfen (purity, 98.8%) at nominal doses of 0
(control), 100, 500 or 1000 mg/kg bw per day for 30 days. The parameters assessed were in-life
observations, body weight and body-weight gain, feed consumption, haematology, clinical chemistry,
urine analysis, organ weights, gross examination of organs and tissues and histopathological
evaluations of the kidney, liver, testes and gross lesions. Body weights and feed consumption were
determined weekly. At the start of treatment, the bodyweights ranged from 8.20–8.93 kg in males and
7.54–8.81 kg in females. The study was performed in accordance with OECD guideline No. 407.
The study design was based on a previous oral study (via capsules) in dogs (one male and
one female per dose) with doses of 0–1000 mg/kg bw per day for 2 weeks (Weaver, 1988). In that
study, body weight, feed consumption, electrocardiograms, enzyme induction, clinical chemistry,
haematology and pathology of organs and tissues did not show any treatment-related changes.
In the present study, the achieved daily intakes of quinoxyfen were 86, 340 and 445 mg/kg bw
per day in males and 130, 305 and 481 mg/kg bw per day in females at nominal doses of 100, 500
and 1000 mg/kg bw per day.
There were no mortalities or signs of toxicity during the study period. Feed consumption was
reduced in all treated males and at doses of ≥ 500 mg/kg bw per day in females. The pattern of feed
consumption was considered by the reporting laboratory to indicate a high degree of unpalatability.
Body-weight loss was observed in males at doses of 500 (11%) and 1000 (35%) mg/kg bw per day and
in females at doses of 500 (20%) and 1000 (30%) mg/kg bw per day compared with values for
controls. Body-weight gain in males at 100 mg/kg bw per day was reduced (30%) compared with
values for controls. There was a very slight statistically non-significant reduction in erythrocyte
count, erythrocyte volume fraction and haemoglobin content in females at the highest dose compared
with pre-test and control values. Clinical chemistry and urine analysis did not show any significant
treatment-related changes. Organ weights were not reported. The testes in the male at the highest
dose and the thymus in the male and female at the highest dose appeared to be small/atrophic on
gross examination. However, microscopic examination of the testes did not reveal any abnormality.
The main histopathological findings were slight multifocal hepatocellular necrosis in females at
≥ 500 mg/kg bw per day and slight (500 mg/kg bw per day) or moderate (1000 mg/kg bw per day)
centrilobular and midzonal hepatocellular vacuolation in both sexes. Moderate multifocal vacuolation
of the proximal convoluted tubule epithelium was observed in both sexes at 1000 mg/kg bw per day.
Severe diffuse lymphoid depletion of the thymus was observed in both sexes at 1000 mg/kg bw per day.
The NOAEL was 86–130 mg/kg bw per day (100 mg/kg bw per day nominal dose) on the
basis of body-weight loss and histopathological changes in the liver [including slight multifocal
hepatocellular necrosis] at 305–340 mg/kg bw per day (nominal dose, 500 mg/kg bw per day).
Impaired body-weight gain and food consumption in the male dog at 100 mg/kg bw per day was
considered to result from unpalatability and was therefore of limited toxicological relevance in setting
the NOAEL (Szabo & Rachunek, 1992).
Groups of four male and four female beagle dogs were fed diets containing quinoxyfen (purity,
98.7%) at nominal doses of 0 (control) 10, 50 or 100 mg/kg bw per day for 90 days. The parameters
assessed were in-life observations, body weight and body-weight gain, feed consumption, haematology,
clinical chemistry, urine analysis, organ weights, gross and histopathological evaluations. The achieved
mean daily compound intakes were 10, 50 and 100 mg/kg bw per day in males and 10, 50 and
101 mg/kg bw per day in females at nominal doses of 10, 50 and 100 mg/kg bw per day. At the start of
treatment, body weights ranged from 8.19 to 10.82 kg in male dogs and 7.48–9.30 kg in female dogs.
No mortalities occurred during the study period. There were no adverse effects on animal
behaviour. Ophthalmological examinations at the beginning and on day 87 of the study did not reveal
any treatment-related ocular defects. A slight transient reduction in food consumption was observed
QUINOXYFEN X-X JMPR 2006