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

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148<br />

Table 5. Chol<strong>in</strong>esterase activity <strong>in</strong> mice fed diets conta<strong>in</strong><strong>in</strong>g az<strong>in</strong>phos-methyl for 104 weeks<br />

Time-po<strong>in</strong>t<br />

Chol<strong>in</strong>esterase activity a<br />

Dietary concentration (ppm)<br />

0 5 20 40<br />

Males Females Males Females Males Females Males Females<br />

Plasma<br />

(μmol/ml per m<strong>in</strong>):<br />

6 months 3.11 5.76 3.33 5.45 2.57 3.08 1.62 1.48<br />

1 year 3.88 6.51 4.81 5.44 2.63 3.27 1.32 1.50<br />

2 years 4.33 4.98 3.95 4.93 2.97 3.86 1.89 1.65<br />

Erythrocytes<br />

(μmol/ml per m<strong>in</strong>):<br />

6 months 1.33 1.16 1.11 1.03 0.88 0.67 0.67 0.63<br />

1 year 1.04 0.87 0.99 0.81 0.45 0.39 0.20 0.20<br />

2 year 0.95 0.79 0.80 0.62 0.54 0.40 0.35 0.32<br />

Bra<strong>in</strong><br />

(μmol/g per m<strong>in</strong>):<br />

2 years 14.7/ 14.4 12.9/ 13.6 12.3 10.6 5.4 4.7<br />

From Hayes (1985); Annex 1, reference 64, amended with reference to orig<strong>in</strong>al data.<br />

a<br />

Results of statistical analysis not specified <strong>in</strong> the report.<br />

2.4 Genotoxicity<br />

The results of studies of genotoxicity with az<strong>in</strong>phos-methyl are summarized <strong>in</strong> Table 7.<br />

An effort was made to evaluate the genotoxicity of a variety of pesticides, with the specific objectives<br />

of compar<strong>in</strong>g different assays <strong>in</strong> vivo and <strong>in</strong> vitro, exam<strong>in</strong><strong>in</strong>g the spectrum of genetic activity<br />

displayed by the selected pesticides and exam<strong>in</strong><strong>in</strong>g the test results <strong>in</strong> relation to other biological and<br />

chemical features of the pesticides. In this research programme, az<strong>in</strong>phos-methyl was used <strong>in</strong> 14 teats<br />

for mutagenicity, exam<strong>in</strong><strong>in</strong>g po<strong>in</strong>t or gene mutations, DNA damage and chromosomal effects. Positive<br />

results for az<strong>in</strong>phos-methyl were seen <strong>in</strong> only two tests: an assay for forward mutation <strong>in</strong> mouse<br />

lymphoma L5178Y cells (only <strong>in</strong> the presence of metabolic activation) and an assay for mitotic recomb<strong>in</strong>ation<br />

<strong>in</strong> Saccharomyces cerevisiae stra<strong>in</strong> D3. Az<strong>in</strong>phos-methyl gave negative results <strong>in</strong> tests<br />

for po<strong>in</strong>t/gene mutation and DNA damage <strong>in</strong> prokaryotes and showed no positive results <strong>in</strong> tests for<br />

chromosomal effects (Waters et al., 1982; Annex 1, reference 64).<br />

2.4 Reproductive toxicity<br />

(a)<br />

Multigeneration studies<br />

Rats<br />

In a two-generation (two litters per generation) study of reproduction, groups of 12 male and<br />

24 female Wistar rats were given diets conta<strong>in</strong><strong>in</strong>g az<strong>in</strong>phos-methyl (purity, 87.2%) at a concentration<br />

of 0 (control), 5, 15 or 45 ppm (equal to 0, 0.33–0.42, 1.02–1.22 and 3.46–7.37 mg/kg bw per<br />

day <strong>in</strong> males and 0, 0.48–0.67, 1.48–2.02 and 4.84–10.27 mg/kg bw per day <strong>in</strong> females). At 45 ppm,<br />

AZINPHOS-METHYL 139–172 JMPR <strong>2007</strong>

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