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

393
Lumbar root ganglion slight degeneration, M/F (%) 0 / 0 NA NA 20 / 0
Sciatic nerve slight degeneration, M/F (%) 20 / 0 NA NA 0 / 0
Lumbar spinal cord, cyst, M/F (%) 20 / 0 NA NA 0 / 0
From Shankar & Stebbins (1999)
F, female; M, male; NA, not analysed.
* p < 0.05
Chronic neurotoxicity was assessed as part of the GLP-compliant, long-term study of toxicity/
oncogenicity with quinoxyfen (Redmond et al., 1995). Groups of 15 male and 15 female rats were
randomly designated at the beginning of the study as a satellite group for assessment of toxicity and
neurotoxicity at approximately 1 year after exposure to diets providing quinoxyfen at nominal doses
of 0, 5, 20 or 80 mg/kg bw per day. Groups of 10 males and 10 females were included in the FOB and
motor activity assays of the study of neurotoxicity. Groups of five males and five females rats were
assigned to the neuropathology portion. FOB and motor activity assessments were performed before
dosing and at 3, 6, 9 and 12 months. Neuropathology examinations were performed on perfusionfixed
tissue of the brain (nine sections) and peripheral nerves from rats in the control group and at
the highest dose.
Quinoxyfen had no effect at any time on hand-held or open-field observations, grip
performance or landing foot splay, either in males or in females. Neither did quinoxyfen affect
any aspect of motor activity, either in males or in females. Occasional variations between test and
control groups were not considered to be treatment-related as they were not consistent over time
and/or were also evident in the pre-dosing phase. The main effect in this study was on body-weight
gains. Although body weights revealed no treatment-related effect when statistically analysed,
body-weight gains were affected in females at the highest dose (80 mg/kg per day). At 3 months,
this group of rats had gained 10% less body weight than the females in the control group compared
with their respective pre-exposure body weights. Also, at 12 months, the females at the highest
dose had gained 11% less body weight than the females in the control group. The results of the
neuropathological evaluation did not indicate that quinoxyfen had any effect on the central and
peripheral nervous system.
The NOAEL for neurotoxicity was 80 mg/kg bw per day, the highest dose tested. The NOAEL
for systemic toxicity was 20 mg/kg bw per day on the basis of reduced body-weight gain, which is
consistent with the main segment of the long-term study in rats (Shankar et al., 1995).
3. Studies on metabolites
The acute oral toxicity of a compound initially identified as 3-hydroxy-quinoxfen (purity
not stated) but subsequently considered to be 2-oxo-quinoxyfen (Pearson & Reeves, 2005) was
investigated in a GLP-compliant study in female Fischer F344 rats. There were no deaths at the only
dose tested, 5000 mg/kg bw (Merkel, 2004).
4. Observations in humans
A review of clinical and health surveillance data for the campaign periods of quinoxyfen
reported no significant health effects related to potential exposure at the workplace.
One of the formulation chemists at the DowElanco research site at Letcombe Regis, was shown to
be sensitized to aqueous solutions containing 10% or more quinoxyfen. No other cases had been found
after checking all employees who have worked with the material. In addition, 20 control individuals
QUINOXYFEN X-X JMPR 2006