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

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2. Toxicological studies
2.1 Acute toxicity
(a)
General toxicity
In a series of GLP-compliant studies, quinoxyfen was shown to be of low acute toxicity in
rats and rabbits exposed orally, dermally or by inhalation (Table 4). The only signs of toxicity at the
limit test doses in the studies of exposure orally or by inhalation were urinary and/or faecal staining
in the perineal area, transient reductions in body weight or decreased activity. No clinical signs were
reported in the study of dermal toxicity.
Table 4. Results of studies of acute toxicity with quinoxyfen
Species Strain Sex Route LD 50
(mg/kg bw)
LC 50
(mg/l air)
Purity
(%)
Vehicle
Reference
Rat F344 M & F Oral > 5000 — 97.4 Corn oil Gilbert (1994a)
Rabbit NZW M & F Dermal (4-h) > 2000 — 97.4 None Gilbert (1994b)
Rat Wistar M & F Inhalation (4-h,
nose-only)
— > 3.38(MMAD,
3.6 μm)
F, female; M, male; MMAD, mass median aerodynamic diameter; NZW; New Zealand White.
97.4 None Beekman
(1994)
(b)
Ocular irritation, dermal irritation and dermal sensitization
Quinoxyfen was not irritating to skin (Gilbert, 1994c), but was slightly irritating to rabbits’ eyes
(Gilbert, 1994d). A study of skin sensitization by the Buehler method gave negative results (Gilbert,
1994e), but a second study using the Magnusson & Kligman maximization method produced clear
evidence of skin sensitization (Johnson, 1995).
2.2 Short-term studies of toxicity
Oral toxicity with quinoxyfen was investigated in 28-day dietary studies in rats and dogs, 90-day
dietary studies in mice, rats and dogs; and in a 52-week dietary study in dogs. Dermal toxicity after
repeat doses was investigated in a 28-day study in rats. No studies with repeated doses administered
by inhalation had been performed.
(a)
Oral administration
Mice
In a GLP-compliant study, groups of 10 male and 10 female CD-1 mice were given diets
containing quinoxyfen (purity, 98.7%) at variable concentrations to give nominal doses of 0 (control),
10, 50, 100 or 500 mg/kg bw per day for 13 weeks. The mice were observed for in-life effects
and parameters including haematology, clinical chemistry, organ weights, gross and microscopic
examination of organs and tissues. Histopathology of all organs and tissues was performed for the
control group and for the group at 500 mg/kg bw per day, but the liver with gall bladder, kidneys,
lungs and gross lesions only were examined for the groups at lower doses. At the start of treatment,
the body weights were 17.3–30.4 g in male mice and 19.5–24.3 g in female mice. The daily intake of
quinoxyfen was calculated from weekly assessments of feed consumption. The achieved mean daily
intakes were 10, 50, 101 and 507 mg/kg bw per day in males and 10, 52, 105 and 523 mg/kg bw per
day in females.
QUINOXYFEN X-X JMPR 2006