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

161
depleted over the test interval, concentrations of cypermethrin in adipose tissue were relatively stable
over the 8 days (Annex 1, reference 33; Crawford, 1976a).
Groups of three male and three female Wistar rats were given cypermethrin ( 14 C-benzyl, transisomer)
as a single oral dose at 2.4 mg/kg bw for males and 3.0 mg/kg bw for females in corn oil.
Again, excretion was rapid in both sexes, with approximately 95% of the administered dose excreted
within 48 h. In contrast to the cis-isomer, there appeared to be no sex differences in the routes of
elimination of the trans-isomer. Residues in adipose tissue of females were two to three times higher
than in the adipose tissue of males. However, residues in the tissues were lower than after dosing
with the cis-isomer (Annex 1, reference 33; Crawford, 1976a). Concentrations in adipose tissue were
approximately half those achieved after similar treatment with the cis-isomer, suggesting that the
trans-isomer is metabolized faster than the cis-isomer. A low level of administered radioactivity
(0.04%) was detected in expired air (Annex 1, reference 33; Crawford, 1976b).
Groups of three male and three female Wistar rats were given cypermethrin (1 : 1 cis : transisomer
ratio, 14 C-cyclopropyl, in corn oil) as a single oral dose at a dose of 1 mg/kg bw for males
and 2 mg/kg bw for females. The rats were killed after 3 days, and concentrations of radioactivity
determined in selected tissues. Rapid elimination of cypermethrin was observed, with a substantial
difference noted in 24-h urinary excretion in males and females. Females excreted considerably
more radioactivity in the urine (55% of administered radioactivity) over the first 24 h relative to
males (32%). After 72 h, total urinary and faecal excretion in both sexes was approximately the
same. Small quantities of radioactivity were expired as 14 CO 2
(approximately 0.1% of administered
radioactivity), which suggested some metabolic breakdown of the cyclopropyl ring. After 3 days,
tissue concentrations in liver, kidney, muscle, brain, blood, skin and remaining carcass were low, but
concentrations of radioactivity in the livers of males was approximately threefold that in females, and
radioactivity in adipose tissue of females was approximately twice that found in males. Radioactivity
in the intestines was approximately three times higher in males than in females, averaging 9% of the
administered dose. Otherwise, the highest residual radioactivity was in fat, but this was less than 1%
of the administered radioactivity (Annex 1, reference 33; Crawford, 1977).
Administration of [ 14 C-benzyl]cypermethrin (cis-isomer) as a single oral dose at approximately
2.5 mg/kg bw to eight female Wistar rats resulted in a residue of approximately 0.3 ppm in the fat
after 8 days. Further studies to 42 days after dosing were performed to evaluate the half-life of the
cis-isomer in fat and the total elimination pattern. At the end of 42 days, residues were observed in
fat which were approximately 10% of the concentrations noted at 8 days. There was a 90% loss of the
material from fat over the 8–42 day interval during which timed samples were taken. From these data
with rats, a half-life of approximately 20–25 days was estimated with respect to removal of residues
from fat after a single oral dose. These half-life values were somewhat longer than those noted with
mice (Annex 1, reference 33; Crawford & Hutson, 1978b).
The fate of orally administered cis- and trans-isomers of cypermethrin was studied in rats g iven
radiolabelled cypermethrin as one of three forms, i.e. 14 C-benzyl; 14 C-cyclopropyl and 14 C-cyano at
doses of 1 to 5 mg/kg bw. Radioactivity derived from the 14 C-benzyl and 14 C-cyclopropyl labelling
was rapidly eliminated, mostly in the urine. Tissue residues were generally very low, e.g. 0.01 μg/g
in brain, with the exception of fat (about 1 μg/g). Residues derived from the cis-isomer tended to be
higher than those derived from the trans-isomer. The rate of depletion of the residues derived from
[ 14 C-benzyl]cis-cypermethrin was rapid (t½ , less than about 1 day) from all tissues except fat (t½,
11–12 days). This residue consisted largely of unchanged cis-cypermethrin. The rapid elimination
of cypermethrin from rats is due primarily to the efficient cleavage of the ester bond giving rise to
CYPERMETHRINS X-X JMPR 2006