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

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were not seen in rats in the control group, a treatment-related effect could not be ruled out (Heimann
& Kaliner, 1983).
Groups of 15 male and 15 female Wistar TNO/W74 rats received cyfluthrin (purity, 83.3%)
emulsified in PEG 400 by gavage daily for 35 weeks. The doses administered ranged from 30 to
80 mg/kg bw per day. The dose was varied intermittently with the purpose of inducing symptoms
of acute toxicity after each dose. For the most part, doses of 60 or 80 mg/kg were given. The rats
were observed daily for clinical signs. Body weights were recorded weekly. At termination clinical
chemistry was performed and mixed function oxidase (MFO) activity of the liver was determined.
Animals were examined macrosopically, organ weights were recorded and liver, kidney, adrenal
gland, brain, spinal cord, and sciatic nerve tissues from five treated and five control rats of each sex
were examined microscopically.
In the treatment group, eight males and two females died, while in the control group two
males and two females died. Throughout the study treated animals displayed signs of acute toxicity
(apathy, ruffled coat, and respiratory disturbances, and in some rats, increased salivation, tremor, and
uncoordinated gait). No paralysis of the extremities was observed. Body-weight gain was reduced
by 20–25% in males, but not in females. Clinical chemistry parameters or MFO activity were
not affected by treatment. Reductions in liver and kidney weight in treated males are considered
secondary to the decreased body weight. Macroscopic and histological examination revealed no
treatment-related changes. However, rats that died during the treatment period were not examined
(Thyssen & Vogel, 1982).
In a concisely reported study to assess the effect of treatment on neuromuscular function,
groups of 10 male Wistar rats received cyfluthrin (purity, 94.5%) as a single oral dose (method of
administration not specified) at 0, 0.1, 0.3 or 1.0 mg/kg bw in the first experiment and 0, 0.01, 0.03
or 0.1 mg/kg bw in the second experiment. Diazepam (5 mg/kg bw) was administered as a positive
control. Cypermethrin (0.1–1.0 mg/kg bw) was used as a reference compound. The ability of the rats
to retain their grip on a tilted plane was assessed at 30 min and at 2, 5 and 7 h after treatment. The
experimental variable was the angle of the plane at which rats lost their grip.
Statistically significant decreases in the angle at which rats lost their grip were noted after
treatment with cyfluthrin. This effect was maximal after 5 h. The effect was observed at doses of
0.03 mg/kg bw and higher. The positive control diazepam and reference chemical cypermethrin
produced similar results (Polacek, 1984).
The present Meeting noted that the effects, although statistically significant (by Student t-test),
were small and not strictly time- or dose-dependent. Furthermore, individual data were not presented
and appropriate statistical analysis was not performed. Therefore the Meeting considered this study
to be inappropriate for assessing neurotoxicity.
In a concisely reported study, the neurotoxic effects (i.e. analgesia, catalepsy, traction,
orientation motility, spontaneous activity, lingomandibular reflex and neuromuscular transmission,
effects on hexobarbital-induced sleep and, pentylenetetrazole-induced convulsions) of single oral
doses of cyfluthrin (purity unknown) at 3, 10 and 30 mg/kg bw were assessed in groups of 5–10 male
CF1 mice and male Wistar rats. The vehicle was PEG 400.
Cyfluthrin at a dose of 30 mg/kg bw followed by hexobarbital at a dose of 100 mg/kg bw
(subcutaneous), induced 60% mortality in mice. No potentiation of hexobarbital-induced sleep was
observed with cyfluthrin at doses of 3 and 10 mg/kg bw. Cyfluthrin at doses of 3 and 10 mg/kg bw had
no muscle-relaxant, analgesic or anticonvulsive properties, and did not affect central coordination or
spontaneous and orientation motility in male CF1 mice. Also in mice, a dose of 30 mg/kg bw lead to
the disappearance of the righting reflex, the inability to grip the support, and prostration, but caused
CYFLUTHRIN AND BETA-CYFLUTHRIN X-X JMPR 2006