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

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No dogs died during the study. Slight tremors were observed in one male in each of the groups
at 800 and 1100 ppm on days 66/67 and 71/86 respectively. Tremors were observed in another male
at 1100 ppm on most days, commencing on day 60. These were described as slight, except for days
76/77 when they reached moderate intensity. Starting on day 49, slight tremors were reported in one
female at 1100 ppm on most days for the remainder of the study. Moderate tremors were reported in
this female during the detailed physical examinations at weeks 7, 9 and 12. There were no ophthalmic
lesions indicative of toxicity attributable to cypermethrin. At 1100 ppm, overall body-weight gain
was reduced in males (24% of control values) and females lost weight (−0.2 kg vs 1.3 kg overall
weight gain in controls). Females at 800 ppm also showed a net body-weight loss in the first 5 weeks
of the study (−0.4 kg vs 0.7 kg weight gain in controls). For the first 3–5 weeks of the study, food
consumption was reduced in both sexes at 800 and 1100 ppm. From week 5, diets were supplemented
with an additional 400 g of food for one female at 800 ppm and one male at 1100 ppm that had been
losing weight. Thereafter, food consumption remained below control levels in males at 800 ppm only.
At 1.5 months, erythrocyte volume fraction was decreased, and mean cell haemoglobin concentration
(MCHC) increased to a statistically significant extent in 1100 ppm males, along with decreases in
erythrocyte numbers and haemoglobin that did not attain statistical significance. Findings were similar
at 3 months, but given that comparable differences existed before testing, they were not attributed to
treatment. Slightly increased chloride concentrations were reported in females at 800 and 1100 ppm
at 1.5 months (110, 111, 112, 113*, 112* mEq/l; *p < 0.05, parametric ANOVA) and in females at
1100 ppm at 3 months (115, 115, 117, 118, 119*;*p < 0.05). The lack of a dose–response relationship
suggests that the findings at 1.5 months were not related to treatment and, given the lack of related
findings, the increase at 3 months is unlikely to have biological significance. There was no treatmentrelated
effect on organ weights, and no macroscopic or microscopic lesions were detected.
The NOAEL was 600 ppm, equal to 20.7 mg/kg bw per day in males and 25.4 mg/kg bw per
day in females, on the basis of tremors in one male at 24.6 mg/kg bw per day and body-weight loss
in females at 34.3 mg/kg bw per day (Daly, 1994).
Groups of four male and four female beagle dogs were fed diets containing cypermethrin (FMC
30980; purity, 95.7%) at a concentration of 0, 100, 200, 600 or 1100 ppm for 12 months. Cypermethrin
was incorporated into the diet as a solution in corn oil. Animals were observed twice daily for clinical
signs, and detailed physical examinations and measurement of body weight and food consumption
were performed before testing and weekly thereafter. Ophthalmoscopic examinations took place at
the beginning and end of the study. Haematology and urine analysis testing were performed before
treatment and at 3, 6 and 12 months, and evaluation of clinical chemistry parameters before testing
and at 6 and 12 months. All animals found dead or killed at the end of the study were subjected
to macroscopic examination, and brain, kidneys, liver, testes/epididymides and thyroid/parathyroid
were weighed and tissues taken for histopathology. The mean daily intake of cypermethrin in the
groups at 100, 200, 600 and 1100 ppm was 2.9, 6.0, 20.4 and 33.9 mg/kg bw per day for males
and 3.3, 5.7, 18.1 and 38.1 mg/kg bw per day for females. Two males at 1100 ppm were killed
after being found in a moribund condition (days 276 and 324) and one male at 600 ppm was found
dead (day 133). Clinical signs in these animals, along with the remaining males and two females
at 1100 ppm, and another male at 600 ppm, included irregular gait and whole-body tremors, and/
or excessive salivation, prostration, incoordination, decreased activity, clonic convulsions, unthrifty
coat and moderate alopecia. There were no treatment-related ophthalmoscopic findings. At 600 ppm,
body weights in males were 7–12% less than those of controls from week 19, and approximately 10%
less than controls in the second half of the study in females. At 1100 ppm, body weights in males
were 4–11% below control values for most of the study, and females weighed 11–24% less than did
the controls from week 16. Only body-weight change in females at 1100 ppm reached statistical
significance with respect to the controls, mainly in the latter half of the study. Food consumption
was decreased by up to 20% in males at 1100 ppm in weeks 1 and 2, and in females at 800 ppm and
CYPERMETHRINS X-X JMPR 2006