Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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without metabolic activation (8%) (Table 30). The negative controls showed incidences of aberrant
cells of 3% and 2%, respectively. At later time-points, no dose-related increase in aberrant cells was
observed. Based on this inconclusive result, a second assay for chromosomal aberration in vitro
with V79 cells was performed (Heidemann & Miltenburger, 1987). Again, at 7 h an increase in the
percentage of aberrant cells was observed at the highest doses with (9.5%) and without metabolic
activation (6.25%). The negative controls showed incidences of aberrant cells of 3.75% and 4.25%,
respectively. For time-point at 18 h, only tests without metabolic activation were performed with 4%
aberrant cells at 12 μg/ml, 5% at 60 μg/ml and 7% at 160 μg/ml. In both studies, the mitotic indices
were greater than 70%. In a similar study with human peripheral lymphocytes, increases in aberrant
cells were observed only at 422 μg/ml without metabolic activation at 48 h and with metabolic
activation at 24 h (statistical significant), a concentration level inducing slight precipitations and
clearly reduced mitotic indices with metabolic activation at 24 h but not at 48 h and without metabolic
activation at 24 h and 48 h (van de Waart, 1991a).
In cytogenic assays in vitro (V79 Chinese hamster cells and human lymphocytes), an increase
in the frequency of chromosome aberrations was detected only at high concentrations, which were
strongly cytotoxic and partly caused precipitation. No clastogenicity was found in an assay for
Table 31. Results of studies of genotoxicity with dimethomorph
End-point Test object Concentration Purity (%) Result Reference
In vitro
Reverse mutation
Salmonella typhimurium
TA98,
TA100, TA1535,
TA1537,
TA1538 and E.
coli WP2uvrA
Forward mutation Hgprt locus in
V79 cells
Chromosomal
aberration
Chromosomal
aberration
Chromosomal
aberration
Cell transformation
Unscheduled
DNA synthesis
In vivo
Micronucleus
formation
31.25–5000 μg/plate in
DMSO ± S9
33–180 μg/ml –S9
133–333 μg/ml +S9
V79 cells 12–160 μg/ml –S9
13–170 μg/ml +S9
V79 cells
Peripheral human
lymphocytes
Syrian Hamster
cells
Male rat hepatocytes
Male and female
mice
160 μg/ml –S9 and
170 μg/ml +S9 for 7 h
and 12–160 μg/ml for
18 h –S9
10–333 μg/ml –S9 at
24 h and 333–422 μg/
ml –S9 at 48 h;
1–422 μg/ml +S9 for
24 h and 422 μg/ml for
48 h +S9
5–50 μg/ml –S9
25–265 μg/ml +S9
94 Negative Brooks & Wiggins
(1989)
98.6 Negative van de Waart (1991b)
NS Increase in aberrant
cells at 7 h
±S9, but not at
later time-points
NS Increase in aberrant
cells at 7 h
±S9 and at 18 h
–S9
98.6 Increase in
aberrant cells at
422 μg/ml ±S9
Heidemann &
Miltenburger (1986)
Heidemann &
Miltenburger (1987)
van de Waart (1991a)
98.7 Negative Poth & Miltenburger
(1986)
2.5–250 μg/ml NS Negative Timm & Miltenburger
(1986)
Single doses of 20,
100, 200 mg/kg bw,
sampling at 24 h, 48 h
and 72 h
NS, not stated; S9, 9000 × g supernatant from rat livers.
98.6 Negative van de Waart (1991c)
DIMETHOMORPH 273–315 JMPR 2007