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

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hepatic APDM activity in males and females at 1500 ppm and in males at 150 ppm. These adaptive
changes in the subcellular portions of the liver were substantially reversed within the 4-week recovery
period. Increased liver weight was not noted on gross examination at the conclusion of the study. A
slight reduction in pituitary weight of males, while statistically significant, was not dose-related. A
slight decrease in female kidney weight was dose-dependent and significantly different from control
values at the highest dose. The decrease in kidney weight in males was slight and not significantly
different from controls in any of the dietary concentrations. Gross and microscopic (including
electron microscopic) examinations of tissues and organs showed no significant differences from the
observations noted in controls. Examination of the sciatic nerve from animals in the control group
and in the group at 1500 ppm showed no changes that could be directly attributable to the presence
of cypermethrin in the diet. Seven of the 16 males at 1500 ppm and 2 of 12 male controls showed
slight changes in myelin that may or may not have been brought about by histological fixation of the
material before examination. The condition of the sciatic nerve of females was similar to that noted
in females in the control group. There were no effects noted in unmyelinated axons in males and
females. Interim histological examination at 30 days, during which time clinical signs of poisoning
were noted, was not performed in this study.
The NOAEL was 150 ppm, equivalent to 150 mg/kg bw per day, on the basis of clinical signs
and reduced body-weight gain and food consumption at 1500 ppm, equivalent to 150 mg/kg bw per
day (Annex 1, reference 33; NOAEL based on JMPR summary of Glaister et al., 1977b).
Hamsters
Groups of male and female Syrian hamsters were given cypermethrin at oral doses exceeding
the median lethal dose (LD 50
) in an attempt to define clinical signs of poisoning and to evaluate histological
damage to the sciatic nerve. At doses of 794 mg/kg bw and higher, all animals showed clinical
signs of poisoning including tremors, abnormal irregular movements, and an unusual gait. As noted
with rats, axon and myelin degeneration was noted in all groups treated. The lesions included swelling
and breaks in the axons and clumping of myelin (Annex 1, reference 33; Butterworth & Clark, 1977).
A series of experiments was performed to further evaluate the neurotoxic potential after shorrtterm,
oral administration of cypermethrin to Chinese hamsters. Clinical examination, functional
testing and enzyme determinations using β-galactosidase and β-glucuronidase were performed. The
functional test consists of measuring the mean slip angle where the animal is maintained on an
inclined plane that steadily increases its angle until the animal can no longer maintain a stationary
position. The average angle of five replicate trials constituted the mean slip angle test.
Groups of 20 male and 20 female Chinese hamsters were given cypermethrin at a oral dose of
40 mg/kg bw followed by a dose of 20 mg/kg bw per day for the following 4 days. Fifteen animals of
each sex served as controls. There was extensive weight loss in all dosed groups and some mortality
was observed, primarily as a result of the initial administration of 40 mg/kg bw. There was a loss of
fur and a dermal ulceration was observed in the early parts of the study. This dermal occurrence was
transient, disappearing rapidly after the treatments were concluded. There was significant weight loss
in the initial phase of the study. However, after the last dose, the surviving animals rapidly gained
weight at a rate consistent with the control animals. There were no effects noted on the mean slip angle
experiment and a marginal increase in β-galactosidase activity was observed in peripheral nerve.
A further experiment with five male and five female Chinese hamsters given cypermethrin at
a dose of 0, 5, 10 and 20 mg/kg bw per day for 5 days showed no mortality over the course of the
study. There was a slower growth of the animals treated at 20 mg/kg bw, which was reversed by the
conclusion of the treatment period. Hyperexcitability was noted in one female at the highest dose.
There were no notable differences in behaviour in any other animals. There was a significant deficit
in the mean slip angle test with females showing an earlier dose-related deficit than noted in males.
CYPERMETHRINS X-X JMPR 2006