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

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tibial nerve (SPTN), trigeminal nerve and trigeminal ganglion after treatment with cypermethrin
for 5 days per week for 4 weeks. Cypermethrin (purity, 98.2%) was given at a dose of 150 mg/kg
bw per day in DMSO (reduced to 100 mg/kg bw per day in arachis oil, after 10 doses, because of
mortality). Alpha-cypermethrin (purity, 96.6%) was given at a dose of 37.5 mg/kg bw per day in
DMSO (also reduced after 10 days to 25 mg/kg bw per day in arachis oil). Five animals of each sex,
treated with either cypermethrin or alpha-cypermethrin, were killed at 2, 3, 4, 5, 6, 8, 10 or 12 weeks
and examined.
Dosing resulted in the death of 56% of the cypermethrin-treated animals and 21% of the alphacypermethrin-treated
animals. The most frequent signs of intoxication included abnormal gait, ataxia,
lethargy, chromodacryorrhoea, salivation and hypersensitivity to sensory stimuli. The β-glucuronidase
and β-galactosidase activities in the SPTN were increased at 5, 6 and 8 weeks, when compared with
controls. The increase was maximal after 5 weeks, and after 12 weeks was comparable to that in the
controls. No significant enzyme changes were found in the trigeminal ganglia and trigeminal nerve
of treated animals.
The second phase was conducted to establish a dose that did not cause peripheral nerve
degeneration in the SPTN, trigeminal nerve and ganglia. Groups of 10 malea nd 10 female rats were
given cypermethrin at a dose of 37.5, 75 or 150 mg/kg bw per day in DMSO or alpha-cypermethrin at
a dose of 10, 20 or 40 mg/kg bw per day in DMSO, on 5 days per week for 4 weeks. A control group
of 10 animals was used. Signs of intoxication similar to those reported in the first phase were seen at
the highest dose. A large increase in β-glucuronidase and β-galactosidase activities in the SPTN was
seen with cypermethrin at 150 mg/kg bw per day and with alpha-cypermethrin at 40 mg/kg bw per
day. In the groups given cypermethrin at 75 mg/kg bw per day or alpha-cypermethrin at 20 mg/kg bw
per day, a small increase in β-galactosidase activity was found in the distal and proximal sections of
the SPTN. The magnitude of the enzyme changes was similar to those in the first phase. Significant
enzyme changes were also found in the trigeminal ganglia and to a lesser extent in the trigeminal
nerve of the groups given cypermethrin at 75 or 150 mg/kg bw per day and alpha-cypermethrin at
20 or 40 mg/kg bw per day. No peripheral nerve degeneration was observed with cypermethrin at
37.5 mg/kg bw or with alpha-cypermethrin at 10 mg/kg bw (JECFA, 1996; Rose, 1983).
Alpha-cypermethrin
3. Biochemical aspects: absorption, distribution, metabolism and excretion
The elimination and retention of alpha-cypermethrin was investigated in male and female
Wistar rats. Groups of five male and five female rats received [ 14 C-benzyl]alpha-cypermethrin
(radiochemical purity, 99.6%) at a dose of 1.9 mg/kg bw in corn oil by gavage, and were sacrificed
96 h later. The distribution of radioactivity in the excreta was 51–54% in the urine and 38–43% in
the faeces. Approximately 75% of the radioactivity in the faeces was unchanged alpha-cypermethrin,
with no evidence of conversion from the cis-isomer to the trans-isomer. Other metabolites identified
in faeces were WL 48801 (a dihydroxy metabolite, 4%), 3-(4-hydroxyphenoxy) benzoic acid (6%)
and 3-phenoxybenzoic acid (less than 1%). The proposed metabolic pathway for alpha-cypermethrin
is provided in Figure 2. More than 75% of the administered radioactivity was excreted within 24 h of
treatment. Low concentrations of radioactivity were found in the tissues (total, 1.5% of administered
radioactivity). The highest concentration was in fat (0.42 and 0.22 μg/g tissue for males and females,
respectively), with the concentration of radioactivity in other tissues at least an order of magnitude
less. There were no sex differences (Hutson, 1982).
The depletion of radiolabel from liver, kidney, skin and fat (parovarian, peri-renal and
subcutaneous) was studied in 24 female Wistar rats given [ 14 C-benzyl]alpha-cypermethrin
CYPERMETHRINS X-X JMPR 2006