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

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weights of males were approximately 84% of the control value and of females were approximately<br />

86% of the control value. Dur<strong>in</strong>g the recovery period, the body weights of the rats at 1600 ppm were<br />

lower than control values, but the difference dim<strong>in</strong>ished with time. Feed <strong>in</strong>takes were not affected<br />

by treatment, but water <strong>in</strong>take was reduced <strong>in</strong> males at 1600 ppm. No treatment-related ophthalmic<br />

f<strong>in</strong>d<strong>in</strong>gs were seen dur<strong>in</strong>g this study.<br />

The haematological exam<strong>in</strong>ations did not give evidence of adverse effects on erythrocytes<br />

or leukocytes. In females only, the clott<strong>in</strong>g time was shortened after 1600 ppm. Cl<strong>in</strong>ical chemistry<br />

revealed a higher prote<strong>in</strong> and an <strong>in</strong>creased cholesterol concentration <strong>in</strong> males and females at ≥ 400 ppm.<br />

At 400 ppm, T3 concentrations were <strong>in</strong>creased <strong>in</strong> males at week 3, but not at the end of the study at<br />

100 and 400 ppm. At 1600 ppm, T3 concentrations and thyroid b<strong>in</strong>d<strong>in</strong>g <strong>in</strong>dex (TBI) were <strong>in</strong>creased <strong>in</strong><br />

week 3 and 12 of the study. Induction of liver enzymes was detected at 400 ppm (cytochrome P450,<br />

N-DEM, O-DEM) and was more pronounced at 1600 ppm <strong>in</strong> both sexes (cytochrome P450, N-DEM,<br />

O-DEM, ECOD, ALD, EROD) (Table 16).<br />

Thiacloprid had no effect on cell counts, or cell size distribution of spleen and lymph node cells.<br />

A slightly <strong>in</strong>creased macrophage activation and <strong>in</strong>crease of lipopolysaccharide (LPS) stimulated cells<br />

<strong>in</strong> the spleen was observed at 1600 ppm. No treatment-related changes of antibody titres for IgA,<br />

IgG and IgM were detected. Tests for a thiacloprid-mediated effect on cell proliferation <strong>in</strong> liver and<br />

kidney cells did not reveal evidence for a specific effect.<br />

Relative liver weights were <strong>in</strong>creased at 400 ppm <strong>in</strong> males and at 1600 ppm <strong>in</strong> both sexes. Thyroid<br />

weights were <strong>in</strong>creased <strong>in</strong> males at the highest dose. Histopathologically, moderate hepatocellular<br />

hypertrophy, associated with a change of per<strong>in</strong>uclear cytoplasm (the cytoplasm exhibited a f<strong>in</strong>e<br />

granular to vesicular structure), probably due to enzyme <strong>in</strong>duction, was seen at 400 ppm and greater.<br />

At the end of the recovery period, only 3 out of 10 males had m<strong>in</strong>imal hepatocellular hypertrophy, but<br />

cytoplasmic changes were no longer found (Table 16).<br />

Table 16. Ma<strong>in</strong> f<strong>in</strong>d<strong>in</strong>gs of the 13-week study <strong>in</strong> rats fed diets conta<strong>in</strong><strong>in</strong>g thiacloprid<br />

F<strong>in</strong>d<strong>in</strong>g<br />

Dietary concentration (ppm)<br />

Males<br />

Females<br />

0 25 100 400 1600 0 25 100 400 1600<br />

Body weight (g):<br />

Week 12 419 395 413 408 351** 220 228 236 209 190**<br />

Week 17r 445 — — — 433 265 — — — 221**<br />

Cholesterol (mmol/l):<br />

Week 3 2.47 2.48 2.49 2.77 3.37** 2.37 2.38 2.46 2.73** 3.71**<br />

Week 12 2.38 2.29 2.49 2.65 3.25** 1.88 1.95 1.92 2.17** 3.45**<br />

Week 17r 2.55 — — — 2.12** 2.50 — — — 2.18<br />

Prote<strong>in</strong> (g/l):<br />

Week 3 62.3 63.2 63.5 65.0* 65.5** 63.1 63.3 65.8* 66.1* 65.6*<br />

Week 12 68.7 70.5 71.0 72.5** 76.5** 66.4 67.4 67.0 69.2 71.3**<br />

Week 17r 72.4 — — — 72.5 71.0 — — — 68.9<br />

T3 (nmol/l):<br />

Week 3 1.59 1.81** 1.87** 1.94** 2.26** 1.70 1.78 1.87 1.86 1.90<br />

Week 12 1.62 1.61 1.58 1.71 2.11** 1.69 1.60 1.70 1.75 1.96<br />

Week 17r 1.58 — — — 1.57 1.60 — — — 1.63<br />

T4 (nmol/l), week 3<br />

Week 3 67 67 71 77** 75* 48 60 65* 57 48<br />

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

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