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

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The no-observed-adverse-effect level (NOAEL) was 100 ppm, equal to 30.1 and 63.9 mg/kg
bw in males and females, respectively, on the basis of reduced feed intake in females and increased
liver weight in both sexes at 1000 ppm (Wirnitzer, 1994).
Groups of five male and five female B6C3F 1
/Bom mice were fed diets containing thiacloprid
(purity, 98.6%) at a concentration of 0, 50, 200, 2000 or 10 000 ppm for 14 days. The objective of
this study was to investigate the effects of the test material on the liver. Clinical signs of toxicity,
body-weight changes, feed consumption and water intakes were recorded at suitable time-points.
Haematological and biochemical investigations were carried out at the end of the study. All animals
received a macroscopic examination at necropsy. The liver was removed, weighed and subjected to
microscopic examination. Liver samples were taken for enzyme determinations. The concentration,
stability and homogeneity of the test material in the diet were acceptable. The mean daily intakes
were equal to 0, 21.6, 84.3, 765.1 and 4143.2 mg/kg bw per day in males, and 0, 29.8, 113.2,
1201.2 and 5449.8 mg/kg bw per day in females at doses of 0, 50, 200, 2000 and 10 000 ppm,
respectively.
Table 12. Main findings of a 14-day study in mice fed diets containing thiacloprid
Finding
Dietary concentration (ppm)
Males
Females
0 50 200 2000 10 000 0 50 200 2000 10 000
Body weight (g) 24 23 23 23 22 20 20 19 19 19
Liver weight (g) 1.36 1.28 1.41 1.56* 1.58** 1.05 1.06 1.06 1.23** 1.39**
Liver weight, relative (%) 5.67 5.48 6.03 6.71 7.08** 5.34 5.44 5.56 6.50** 7.41**
Hepatocytes, hypertrophy 0 0 41.3 42.0 53.0 0 11.0 0 31.3 52.4
Average grade
Hepatocytes, fatty change 11.0 21.0 31.0 41.8 31.3 31.0 21.5 41.3 41.5 41.8
Average grade
ECOD (nmol/g per min) 11.0 10.8 12.8 30.4 124.1 15.2 15.8 26.6 84.7 208.4
EROD (nmol/g per min) 0.50 0.56 0.75 0.90 3.53 0.57 0.50 0.71 2.43 2.99
ALD (nmol/g per min) 21.9 15.1 34.8 42.9 109.2 18.0 29.2 48.0 197.6 273.1
EH (nmol/g per min) 650 570 558 461 736 358 239 277 385 550
GST (μmol/g per min) 299.9 354.4 367.8 555.6 1 672.2 140.0 144.5 180.0 641.3 1 500.0
UDP-GT (nmol/g per min) 280 275 270 354 679 242 226 270 370 509
From Kroetlinger (1997)
* p < 0.05; ** p < 0.01.
ALD, aldrin epoxidase; ECOD, 7-ethoxycoumarin deethylase; EH, epoxide hydrolase; EROD, 7-ethoxyresorufin
deethylase; GST, glutathione-S-transferase; UDP-GT, uridine diphosphate glucuronosyl transferase.
No animals died during the study or showed clinical signs of toxicity. Body weights and feed
intakes were not affected by treatment. Water intakes were reduced in males at 2000 ppm and greater.
In males at the highest dose, there was a significant reduction in the mean cholesterol value and a
significant increase in the mean protein value, whereas in females, there was a significant reduction
in mean albumin, cholesterol and bilirubin values at the highest dose. Dose-dependent enzyme
induction was evident in the liver of both sexes at dietary concentraztions of ≥ 2000 ppm with some
marginal effects at 200 ppm (Table 12). No gross findings were seen at necropsy. Mean liver weight
(absolute and relative) was increased in both sexes at ≥ 2000 ppm (Table 12). Microscopy revealed
hypertrophy of the centrilobular hepatocytes in males at ≥ 200 ppm and in females at ≥ 2000 ppm.
The lipid content in hepatocytes was increased in both sexes at ≥ 2000 ppm.
THIACLOPRID X-X JMPR 2006