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

181
Alkaline Comet
assay
D. melanogaster
larvae (first instar); brain
ganglia and anterior
m id-gut
0.004–0.5 μg/ml; killed
after 96 ± 2 h exposure in
the food
NR, not reported; DMSO, dimethyl sulfoxide.
a
With and without metabolic activation (preparation from rats).
98.5 Positive e Mukhopadhyay
et al. (2004)
b
With and without mouse liver subcellular activation (preparation from six strains of PCB-treated mice)
c
Summarized from JMPR 1979 evaluation (Annex 1, reference 33); these details not provided therein.
d
Positive control, cyclophosphamide at 100 mg/kg bw; negative control, DMSO.
e
A dose-related increase relative to controls was seen in tail DNA, tail length and tail moment in the single-cell gel
e lectrophoresis (Comet) assay for both tissues examined.
f
Increased tail length (50 and 200 μg/ml), increased tail intensity (10 and 200 μg/ml) and increased tail moment
(200 μg/ ml) were observed, but as dose–response relationships were lacking, only the results at 200 μg/ml were
c onsidered to significantly increase DNA damage in human lymphocytes in this test.
2.5 Reproductive toxicity
(a)
Multigeneration studies
Rats
Groups of 30 male and 30 female Wistar rats received diets containing cypermethrin (purity,
98%) at a concentration of 0, 10, 100 or 500 ppm for 5 weeks before mating and then throughout
pregnancy and lactation for three successive generations. Two litters were bred per generation. The
first litters were discarded at weaning. Males and females from the second litter were randomly
selected to breed the next generation. A significant reduction in body-weight gain was seen in the
male and female parent rats receiving cypermethrin at 500 ppm in all three generations. This was
correlated with a reduction in food consumption. Litter size was reduced at 500 ppm in the F 1a
litter
at birth and after 7 and 21 days. Litter weights were reduced at 500 ppm in the F 1a
litters on days 7,
14 and 21 of lactation. No other effects on fertility or reproduction parameters were found and no
compound-related gross or microscopic pathological findings were noted in any rats.
The NOAEL for parental toxicity was 100 ppm, equivalent to 7.5 mg/kg bw per day, on the
basis of reduced body-weight gain and food consumption at 500 ppm, equivalent to 38 mg/kg bw per
day. The NOAEL for reproductive toxicity was 100 ppm, equivalent to 7.5 mg/kg bw per day, on the
basis of reduced litter size and litter weights at 500 ppm, equivalent to 38 mg/kg bw per day (JECFA,
1996; Hend et al., 1978; Fish, 1979; Thorpe, 1985).
Groups of 15 male and 30 female Wistar (Alderley Park) rats received diets containing cypermethrin
(purity, 91.5%, cis : trans 55 : 45) at a concentration of 0, 50, 150 or 750 ppm for 11–12
weeks before mating, then throughout pregnancy and lactation for three successive generations. Rats
in the F 0
group receiving the highest dose were initially treated at 1000 ppm, but due to clinical signs
of neurotoxicity in most animals in the first 3 weeks of the study, this was reduced to 750 ppm after
12 weeks. Clinical observations were performed at least daily, and food consumption was recorded
weekly. Body weights were recorded weekly in the period before mating and during pregnancy, then
every 4 weeks until termination (but weekly during pregnancy). Pup body weights were recorded on
postnatal days 0, 4, 10, 21 and 28. Two litters were bred per generation, with males and females from
the second litter randomly selected to breed the following generation. Parental males were sacrificed
after mating for the second litters of each generation, and parental females were killed after weaning
(21 days postpartum, except for the F 1a
litters that were separated from their mothers after 28 days).
Gross necropsies were performed on all parental animals and 50% of each generation of offspring,
the remainder being discarded. Selected organs were weighed and tissues taken for histopathology
CYPERMETHRINS X-X JMPR 2006