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

163
in the heart (67.6 and 88.7 ng equivalents/g tissue in males and females respectively), spleen (64.2
and 63.6 ng equivalents/g tissue), muscle (35.2 and 51.7 ng equivalents/g tissue) and bone (72.8 and
44.4 ng equivalents/g tissue). There was no detectable radioactivity in the brain of female rats and only
a very low concentration was detected in brains in males (mean, 13.4 ng equivalents/g tissue). Of the
individual organs examined, the highest residual radioactivity was found in the gastrointestinal tract
(mean, 6405 ng equivalents), liver (mean, 5820 ng equivalents) and kidney (mean, 795 ng equivalents).
The high concentration of radioactivity found in fat, skin, ovaries and adrenal glands is consistent with
the lipophilic nature of cypermethrin. The pyrethroid group of insecticides is known to undergo extensive
metabolism in mammals (Casida & Ruzo, 1980), resulting in metabolites of a less lipophilic nature that
will therefore be more rapidly excreted than the parent compound. The accumulation of radioactivity
in the liver and kidney found in this study was consistent with these processes of metabolism and
excretion. High concentrations of radioactivity were also found in the gastrointestinal tract, reflecting
its role in absorption. Less radioactivity was accumulated in the remaining tissues studied, the lowest
concentrations being located in the brain (Annex 1, reference 37; Hall et al., 1980).
A study of bioaccumulation was undertaken to establish the rate and extent of accumulation of
cypermethrin-derived 14 C label in a selected range of tissues during a daily oral dosing regime and
also the rate of elimination of 14 C residues after the attainment of steady-state tissue concentrations.
Sixty female rats were dosed orally with 14 C-benzyl-labelled cypermethrin (50 : 50 of cis : trans),
at a dose of 2 mg/kg (2 μCi/kg) bw in maize oil (2 ml/kg bw) for up to 70 consecutive days. A
group of treated (three) and untreated (one) animals was sacrificed at prescribed intervals during
the dosing regime in order to monitor the rate and extent of bioaccumulation of 14 C in liver, kidney,
adipose tissue, blood (whole blood and plasma), skin and ovaries. The elimination of radioactivity
from fat demonstrated biphasic characteristics. This was associated with a rapid elimination of
residues of trans-cypermethrin coupled with a slower elimination of the cis-isomer. These elimination
characteristics did not allow a simple half-life value to be calculated for elimination of radioactivity
from fat. However, as the relative proportions of cis- and trans-isomers in fat were monitored from
day 70 of the study, it was possible to determine the independent half-lives for both isomers. At
the termination of dosing, the relative proportions of cis- and trans-isomers in fat were 88.25% to
11.75%. The half-lives of elimination of cis- and trans-cypermethrin from fat were calculated by
linear regression analysis to be 18.24 and 3.43 days respectively.
After daily dosing for 70 consecutive days, the extent of bioaccumulation of radioactivity in each
tissue analysed was shown to reach a plateau. The extent of accumulation, expressed as μg equivalents
of cypermethrin per gram of tissue (as mean ± standard deviation [SD] values from a group of three
rats), was: liver, 0.97 ± 0.31; kidneys, 0.65 ± 0.24; fat, 3.91 ± 0 25; blood, 0.35 ± 0.13; plasma, 0.64
± 0.28; skin, 1.86 ± 0.14; and for each ovary, 0.03 ± 0.01 μg equivalents. Such concentrations of
radioactivity in ovaries were similar to background values. In addition, the degree of accumulation of
14
C-label in the sciatic nerve was determined by analysing nerves isolated from treated animals given
cypermethrin as 56 to 70 daily doses. The extent of accumulation of radioactivity did not exceed
0.05 μg equivalents of cypermethrin per nerve, representing a level of radioactivity similar to the
background value. After the termination of dosing, the remaining groups of treated and untreated
rats were sacrificed at prescribed intervals for 50 days. Tissue residue concentrations of radioactivity
were monitored and the rate of elimination of 14 C-label from each tissue was determined. After the
cessation of dosing, the liver, kidney and blood 14 C-residue concentrations fell rapidly and reached
control background levels within 29, 8 and 15 days respectively. With regard to skin, a much slower
elimination of radioactivity was observed, with half of the radioactivity being eliminated by 18.7 days
after dosing (Annex 1, reference 37; Jones, 1981).
Male and female Wistar rats were given oral doses of 14 C-benzyl cypermethrin or 14 C-cyclopropyl
cypermethrin in corn oil as a single dose of 200 mg/kg bw or repeated doses of 2 mg/kg bw per day
CYPERMETHRINS X-X JMPR 2006