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263<br />

Table 28. Results of studies of genotoxicity with cyromaz<strong>in</strong>e<br />

End-po<strong>in</strong>t Test object Concentration o Purity (%) Results GLP or<br />

QA<br />

In vitro<br />

Reverse mutation S. typhimurium TA98, TA100, TA1535,<br />

TA1537<br />

Reverse mutation S. typhimurium TA1538 & E. coli<br />

WP2uvrA<br />

Gene mutation, mitotic<br />

gene conversion & mitotic<br />

recomb<strong>in</strong>ation<br />

20–5000 μg/plate, <strong>in</strong> DMSO 97.5 Negative a,b GLP &<br />

QA<br />

20–5000 μg/plate, <strong>in</strong> DMSO 97.5 Negative a,c GLP &<br />

QA<br />

Saccharomyces cerevisiae D7 375–3000 μg/ml, <strong>in</strong> DMSO 98.9 Negative a,d GLP &<br />

QA<br />

Gene mutation Mouse lymphoma cells, L5178Y, Tk +/- 50–500 μg/ml, <strong>in</strong> culture medium, 4-h exposure 96.2 Negative a,e GLP &<br />

QA<br />

Gene mutation Ch<strong>in</strong>ese hamster, V79 cells, Hprt locus 25–1000 μg/ml, −S9, <strong>in</strong> ethanol, 21-h exposure<br />

100–4000 μg/ml, +S9, <strong>in</strong> ethanol, 5-h exposure<br />

Chromosomal aberration Human peripheral blood lymphocytes 62.5, 125, 250, 500 and 1000 μg/ml <strong>in</strong> DMSO, ± S9,<br />

3-h treatment, harvest<strong>in</strong>g 46 h after the end of treatment<br />

98.9 Negative a,f GLP &<br />

QA<br />

96.2 Negative a,g GLP &<br />

QA<br />

Reference<br />

Deparade<br />

(1988)<br />

Deparade<br />

(1990)<br />

Hool (1984)<br />

Beilste<strong>in</strong><br />

(1985)<br />

Dollenmeier<br />

(1986)<br />

Unscheduled DNA synthesis Rat (F344) primary hepatocytes 1–10 -4 mg/ml <strong>in</strong> DMSO, 18-h exposure NR Negative h QA Tong (1982)<br />

Unscheduled DNA synthesis Mouse (male CD-1) primary<br />

1–10 -4 mg/ml <strong>in</strong> DMSO, 18-h exposure NR Negative i QA Tong (1983)<br />

hepatocytes<br />

In vivo<br />

98.9 Negative k — Hool (1980)<br />

Nucleus anomalies j (BM cells) Ch<strong>in</strong>ese hamster (three male + three<br />

female/group)<br />

Micronucleus test (BM cells) Mouse (Tif:MAGf SPF, NMRI derived)<br />

(five male + five female/group)<br />

Spot test Mouse (males: T-stock, females:<br />

C57Bl/6)<br />

Two oral doses at 2000, 4000 and 8000 mg/kg bw (24 h<br />

apart) <strong>in</strong> CMC<br />

S<strong>in</strong>gle oral doses of 360 and 1080 mg/kg bw <strong>in</strong> CMC-<br />

Sampl<strong>in</strong>g time: 24, 48 and 72 h after treatment<br />

S<strong>in</strong>gle <strong>in</strong>traperitoneal. doses at 150, 300 and 600 mg/kg<br />

bw <strong>in</strong> sesame oil<br />

96.3 Negative l GLP &<br />

QA<br />

96.2 Inconclusive m GLP &<br />

QA<br />

Dom<strong>in</strong>ant lethal Mouse (Tif:MAGf SPF, NMRI derived) S<strong>in</strong>gle oral doses at 226 or 678 mg/kg bw <strong>in</strong> PEG 400 98.9 Negative n — Hool (1981)<br />

CMC, carboxymethyl cellulose; DMSO, dimethyl sulfoxide; GLP, good laboratory practice; NR, not reported; QA, quality assurance; S9, S9, 9000 × g supernatant from livers of male rats.<br />

a<br />

With and without metabolic activation.<br />

b<br />

Cyromaz<strong>in</strong>e was 264assayed twice us<strong>in</strong>g the standard plate <strong>in</strong>corporation protocol over a dose range of 20-5000 μg/plate, ±S9 prepared from Aroclor-<strong>in</strong>duced male RAI rats. The<br />

experimental protocol essentially complied with OECD TG 471 (1997).<br />

Strasser<br />

(1985)<br />

Strasser<br />

(1987)<br />

Strasser<br />

(1986)<br />

CYROMAZINE X-X JMPR <strong>2006</strong>

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