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

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appearance, behaviour, signs of toxicity, morbidity and mortality. Each week, all rats were examined
in detail, including palpation for tissue masses. Body weights were estimated before dosing and
weekly thereafter, and food consumption was estimated weekly. A functional observational battery
(FOB) test was performed 1 week before administration of the test materials, at the time of peak
effect after administration of the test materials (9–11 h for diazinon, 1 h for triadimefon) and 7 and
14 days after administration (of diazinon) on the 10 rats intended for neurological testing. Blood
samples were obtained at the estimated time of peak effects and at 14 days for the five rats designated
for cholinesterase testing in each group, and plasma and erythrocyte cholinesterase activity was
determined (by colorimetric assay), while brain cholinesterase activity was estimated in whole brain
samples at termination 14 days after administration. The rats used for neurological examination
(survivors to termination and decedents) were subjected to necropsy. Sections were made at 10 levels
of the brain, cervical, thoracic, lumbar and sacral spinal cord with ganglia and right and left sciatic
nerves, right and left fibular nerves, right and left tibial nerves and right and left lateral cutaneous
sural nerves, and the Gasserian ganglion. Sections were also taken of skeletal muscle from the right
thigh, eyes with the optic nerve and any gross lesions identified. Only five rats per group in the
groups receiving diazinon at 600 mg/kg bw, the control group and those treated with triadimefon
were processed for histopathological examination.
Two males and one female died during the study. These deaths were attributed to treatment with
diazinon, and all occurred at the highest dose. There was a single accidental death in the group of
five rats at 300 mg/kg bw and intended for cholinesterase measurement during blood sampling. One
control animal was removed from the study as it was thought to have been wrongly dosed, since it
had signs of cholinergic poisoning and low cholinesterase activity. The clinical observations included
chromodacryorrhoea, reduced activity and tremors at a dose of 300 mg/kg bw, while the group
at 600 mg/kg bw also had chromorhinorrhoea, diarrhoea and pallor. Significant decreases in bodyweight
gain were observed in males at doses equal to or greater than 300 mg/kg bw, while no effects
were observed on body weight or weight gain in the females. Food consumption was decreased in
males at doses equal to or greater than 300 mg/kg bw and in females at doses equal to or greater than
150 mg/kg bw. In both males and females, effects on parameters of the FOB test were seen only at
the estimated time of peak effect after administration of the test materials (9–11 h for diazinon, 1 h
for triadimefon) and not on day 7 or 14 after exposure.
The autonomic parameters affected by diazinon at the time of peak effects in males were faecal
consistency and soiled fur at doses equal to or greater than 150 mg/kg bw, and these effects were
dose-related. Increased salivation, staining of the nose and repeated opening and closing of the mouth
were observed at doses equal to or greater than 300 mg/kg bw. Additionally, impaired respiration,
lachrymation and staining of the mouth were seen at 600 mg/kg bw. In females, repeated opening
and closure of the mouth were observed at doses equal to or greater than 150 mg/kg bw and altered
faecal consistency, soiled fur and staining of the nose were observed at doses equal to or greater
than 300 mg/kg bw. At the highest dose, impaired respiration and lachrymation were observed. The
neuromuscular parameters that were affected in males were: abnormal gait at equal to or greater than
150 mg/kg bw; ataxic gait, impaired righting reflex, impaired hindlimb extensor reflex and decreased
hindlimb footsplay at doses equal to or greater than 300 mg/kg bw and reduced forelimb grip strength
at 600 mg/kg bw. In the females, ataxic and abnormal gait was observed at equal to or greater than
150 mg/kg bw and impaired righting reflex at equal to or greater than 300 mg/kg bw. Impaired hindlimb
extensor reflex, abnormal hindlimb positioning when held by the tail and reduced forelimb and hindlimb
grip strength were observed at 600 mg/kg bw. Central nervous system excitability parameters were
also affected. In males, tremors were observed in the home cage and open field at equal to or greater
than 300 mg/kg bw, as was twitching or muscle fasciculation. At 600 mg/kg bw, the arousal level was
decreased. Females had tremors in the home cage at the highest dose only and in the open field at doses
equal to or greater than 300 mg/kg bw. Twitching in the open field was seen at the highest dose and a
DIAZINON X-X JMPR 2006