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

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Table 9. Results of studies of genotoxicity with alpha-cypermethrin
End-point Test object Concentration Purity (%) Results Reference
In vitro
Forward and reverse
gene mutation b, g
S. cerevisiae
XV185-14C
31.25–4000 μg/ml in DMSO a 95.8 Negative Brooks (1984)
Reverse mutation
(Ames) f
Forward mutation f
Chromosomal
aberration f
In vivo
Chromosomal
aberration g
S. typhimurium TA98,
TA100, TA1535,
TA1537, TA1538;
E. coli WP2 uvrA
L5178Y mouse
lymphoma cells
Human peripheral
lymphocytes
Rat femoral bone
marrow
31.5–5000 μg/ml in acetone a 95.6 Negative c Brooks &
Wiggins
(1993a)
3.3–50 μg/ml in DMSO a 95.4 Negative Vanderwaart
(1994)
−S9: 93.75–1000 μg/ml;
+ S9: 125–1000 μg/ml in
acetone
Micronucleus
formation h Mouse 1–10 mg/kg bw single oral
dose in corn oil
Alkaline elution Rat liver 40 mg/kg single oral dose in
analysis g 20% DMSO, 6 h exposure
95.6 Negative d Brooks &
Wiggins
(1993b)
2–8 mg/kg bw, single oral 95.8 Negative Clare &
dose in corn oil e Wiggins (1984)
95.4 Negative Vanderwaart
(1995)
96.5 Negative Wooder (1981)
DMSO, dimethylsulfoxide; S9, 9000 × g supernatant from livers of male Sprague-Dawley rats.
a
With and without metabolic activation.
b
In log- and stationary-phase cultures; positive controls were cyclophosphamide (25 mg/ml in water) and
4-nitroquinoline-N-oxide (1 mg/ml in DMSO).
c
No cytotoxicity.
d
Precipitation was seen.
e
Initially doses of 10, 20 or 40 mg/kg were used, but the animals exhibited severe signs of toxicity and the experiment
was terminated at these doses. Surviving females were evaluated for chromosomal damage and none was observed.
f
Two independent experiments performed; positive controls included; GLP and QA statements included.
g
Positive controls included; QA but no GLP statements included.
h
Positive controls included; GLP and QA statements included.
4.5 Reproductive toxicity
(a)
Developmental toxicity
Rats
In a dose range-finding study, five pregnant female Sprague-Dawley rats received alphacypermethrin
(purity, 95.6%) at a daily dose of 0, 3, 9, 15 or 18 mg /kg bw in corn oil by gavage
during days 6–15 of gestation. Maternal body weights, food consumption and clinical observations
were recorded. On day 20 of gestation the females were killed and the fetuses were weighed, sexed
and externally examined. Four dams at 18 mg/kg bw per day and one dam at 15 mg/kg bw per day
showed hindlimb splay and unsteady gait during dosing. Mean body-weight gain was reduced in a
dose-related manner at 9, 15 and 18 mg/kg bw per day and food consumption was reduced in rats
at at 15 and 18 mg/kg bw per day. No other treatment-related abnormalities were observed (JECFA,
1996; Irvine & Twomey, 1994).
In the definitive study, groups of 24 pregnant female Sprague-Dawley rats received alphacypermethrin
(purity, 95.6%) at a dose of 0, 3, 9 or 18 mg/kg bw per day in corn oil by gavage during
CYPERMETHRINS X-X JMPR 2006