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

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of cypermethrin (purity, 97%; containing approximately equal proportions of cis- and trans-isomers),
were studied in male and female adult Long Evans rats, employing a functional observational battery
(FOB) and an automated measure of motor activity. Cypermethrin was administered as a single dose
at 0, 20, 60 or 120 mg/kg bw by gavage to groups of eight males and eight females for the FOB, and
groups of 12 males and 12 females for the tests for motor activity. For the tests for motor activity, the
highest dose was reduced to 100 mg/kg bw owing to lethality in the FOB study. As preliminary studies
indicated that different effects were evident at different times after dosing, FOB assessments were
made at 1.5 h and 3 h after dosing, as well as immediately before dosing, with motor activity testing
performed at 3, 24 and 48 h after treatment. One male and six female rats treated with cypermethrin
at 120 mg/kg bw died on the day of dosing, as did two males at 100 mg/kg bw. Treatment with
cypermethrin affected gait, muscle function, tone and equilibrium, and produced autonomic signs and
burrowing behaviours, with female rats generally being the more sensitive sex. Animals were often
observed lying flat in the home cage, with tremors; they displayed excessive lateral head movements
on the open field; and profuse salivation was observed. At ≥ 60 mg/kg bw, salivation, choreoathetosis,
altered righting reflex, splayed limbs and flattened posture were observed; urination, landing footsplay
and click response were increased; and arousal, grip strengths, touch response and tail-pinch
response were decreased. Resistance to removal from the home cage, and gait abnormalities were
increased, and total activity counts were decreased at 20 mg/kg bw and above. Effects were generally
present in both sexes, and peaked within a few hours of dosing. Notably, salivation and increased
removal reactivity (males) peaked at 1.5 h, subsiding by 3 h, at which point motor and sensory effects
were the most evident, with motor effects persisting for 1 to 2 days after dosing, particularly in
females. A NOEL could not be determined (McDaniel & Moser, 1993).
In a study on the effect of cypermethrin on spontaneous motor function, groups of 8–18
male Long Evans rats were given cypermethrin (49 : 51, cis : trans-isomer ratio) at a dose of 0.1 to
120 mg/ kg bw by gavage. A marked decrease in spontaneous motor function was seen at 40 mg/kg
bw. The dose producing the minimum reliably detectable (30%) decrease in activity was estimated
to be 10 ± 1.3 mg/kg bw, and the highest no-effect level was 4.3 mg/kg bw (95% confidence limits,
2.0–6.5 mg/kg bw) (Wolansky et al., 2006).
In a paired feeding study to examine the neurotoxicological effects of high dietary concentrations
of cypermethrin, groups of 10 male rats were fed diets containing cypermethrin (45 : 55, cis : transisomer
ratio) at a concentration of 0, 1250, 2500, or 5000 ppm for 14 days. Growth was monitored
and clinical evaluations for adverse behaviour were recorded during the course of the study. Gross
pathology on tissues and organs and microscopic examination of the sciatic nerve were performed
at the conclusion of the study. At 5000 ppm, mortality was observed with all rats either dying or
being sacrificed in a moribund condition within the first week. At 2500 ppm, six out of 10 rats died
before the conclusion of the study. There was no mortality in the group at the lowest dose. Clinical
signs of neurotoxicity were characterized by an impaired ability to walk and splayed hind limbs. In
extreme cases, clinical signs of ataxia and paralysis were reported. Other clinical signs included:
hypersensitivity to external stimuli, gross disorientation and convulsions, the latter generally seen at
high doses. The neurotoxic signs of poisoning observed in the group at 1250 ppm after day 3 were
spontaneously reversed by day 9 when all surviving animals that were initially affected appeared to
be normal. Remission of ataxia in the group at 2500 ppm was also noted within 11 days of treatment.
Growth reduction was observed in all animals in the study. At the lowest dose, the rate of growth was
delayed for the first few days after which time the rate was consistent with that of controls for the
remainder of the study. The absolute body weight of the treated animals, however, was significantly
lower than that of the controls at the conclusion of the 2-week study. Reduction in body weight was
consistent with reduction in food consumption. Ultrastructural changes in the sciatic nerve were
CYPERMETHRINS X-X JMPR 2006