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

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for up to 70 days. Signs typical of pyrethroid toxicity were observed in rats dosed with 200 mg/kg bw,
comprising salivation, hunched back, splayed gait, ataxia, convulsions and hypersensitivity, with the
usual time of onset 1.5–2 h after dosing. At 200 mg/kg bw, minimal amounts of 14 CO 2
were detected in
the expired air. For males/females treated with 200 mg/kg bw cypermethrin, recovery of administered
radioactivity in the urine and faeces, respectively, was 29/33% and 55/59% for the 14 C-benzyl label,
and 41/56% and 46/34% for the 14 C-cyclopropyl label, suggesting that 29–56% of the dose was
absorbed in most instances, as most of the 14 C in the faeces was present as unchanged cypermethrin.
Less than 1% of the administered radioactivity remained in the animals 7 days after dosing. The
distribution of radioactivity in the tissues was similar at 7 days after a single dose of 200 mg/kg bw
cypermethrin labelled at either position, and 24 h after 28 daily doses of 2 mg/kg bw per day 14 C-
benzyl-labelled cypermethrin, and was also similar in males and females. The highest concentrations
of radioactivity occurred in fat, followed by skin, liver, and kidney, with the concentrations in
female gonads also relatively high after either treatment regime, and in the adrenals after repeated
dosing at 2 mg/kg bw per day. Seven days after the single dose of 14 C-cyclopropyl cypermethrin at
200 mg/kg bw, radioactivity in the liver and intestines of males was approximately three times that
of females, and an extremely high level in the spleens of males was not explained (not determined
in other groups). In a study of bioaccumulation and elimination in female rats dosed with 14 C-benzyl
cypermethrin at 2 mg/kg bw per day, radioactivity accumulated rapidly in the liver, kidney, fat, blood,
skin and ovaries in the first week of dosing, followed by a slow increase that continued throughout
the next 9 weeks of treatment. The concentrations of radioactivity in the plasma, liver and kidneys
approximately doubled between 4 and 10 weeks of treatment, but concentrations in fat and skin did
not change markedly in this interval (Rhodes et al., 1984).
The distribution, kinetics and excretion of 14 C-phenyl cypermethrin at a dose of 3.0 mg/kg
bw, diluted with unlabelled alpha-cypermethrin (purity, > 98%), were evaluated in female HAN-Ibm
Wistar rats after intravenous administration via the tail vein. Radioactivity excreted in the urine and
faeces within 120 h of treatment amounted to 89.7% of the administered dose, comprising 61.3%
in the urine and 28.4% biliary excretion into the faeces, with approximately 80% of administered
radioactivity excreted in the first 48 h. The half-life of radioactivity in the blood was 5.9 h, with similar
half-lives of 4.8–9.9 h in most organs and tissues, the exceptions being fat (half-life, > 24 h) and the
skin from the back region (half-life, 12.8 h). After 120 h, liver, ovaries, kidneys, sciatic nerve and skin
from the back region retained higher concentrations of radioactivity than blood, but concentrations
in these tissues (0.04–0.1 μg/g) were much less than the concentration in fat (1.45 μg/g) (Van Dijk
& Burri, 1993).
Groups of male beagle dogs were given 14 C-benzyl cypermethrin or the individual 14 C-benzyl
labelled cis- and trans-isomers of cypermethrin, orally, at a dose of 2 mg/kg bw. Elimination of
radioactivity from all animals was rapid, although differences in data from individual dogs precluded
a complete evaluation of the rate of elimination. Differences in the rates of elimination of the
individual dogs in the study may have been due to differences in absorption, as cypermethrin was
given orally in a capsule with no solvent. Tissue residues observed 4 days after oral administration of
cypermethrin were extremely low. Most of the excreted material was found in the faeces (80%) with
urine containing only 11% of the administered dose. As with other species, residues of cypermethrin
were observed in fat, approximating 2% of the administered dose (this residue was estimated to be
0.3 ppm based upon total adipose tissue of the dog) (Annex 1, reference 33; Crawford, 1979b).
In a study of excretion in humans, cypermethrin (purity, 98.1–98.5%; cis : trans 1 : 1) was
administered to four male subjects as a single oral dose at 0.25–1.5 mg in corn oil contained in
a capsule. The urinary excretion of 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid
CYPERMETHRINS X-X JMPR 2006