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

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(iv)
Comparative study on liver effects in rats
In a short-term study on liver effects, groups of five female Wistar (HsdCpb:WU) rats
received diets containing thiacloprid or the metabolites thiacloprid-sulfonic acid amide and
thiacloprid-sulfonic acid Na-salt at a concentration of 1000 ppm for 7 days. As controls, five
female rats were fed the standard diet. The test compounds were homogeneously distributed and
chemically stable for at least 8 days in the diet, and their concentrations in the diet agreed with
the target values within defined limits. The daily intakes were 113.08, 125.27 and 115.67 mg/kg
bw per day for thiacloprid, thiacloprid-sulfonic acid amide and thiacloprid-sulfonic acid Na-salt,
respectively.
No clinical signs were observed, and mortality was not increased in any dose group. The
feed consumption per animal and per kg body weight was decreased at all doses. Body-weight
development was not influenced by the treatment with the metabolites thiacloprid-sulfonic acid
amide and thiacloprid-sulfonic acid Na-salt. Treatment with thiacloprid resulted in a decrease of
body-weight development. After 7 days of treatment in this group, the difference to the controls in
body-weight gain was –37%.
Table 41. Selected findings in a comparative study of liver effects in rats given diets containing
thiacloprid or its metabolites at a concentration of 1000 ppm for 7 days
Diet
Control Thiacloprid Thiacloprid-sulfonic
acid amide
Thiacloprid-sulfonic
acid Na-salt
Body weight (g), day 8 143 138 146 149
Body-weight gain (g) 22 14** 26 28
Liver weight (g) 6.809 8.478** 7.018 7.316
Relative liver weight (%) 4.772 6.145** 4.820 4.911
ECOD (nmol/g per min) 4.0 20.9** 4.2 3.7
EROD (nmol/g per min) 0.44 0.50 0.50 0.44
ALD (nmol/g per min) 31.0 92.7** 32.7 29.5
EH (nmol/g per min) 322 1478** 437 445
GST (μmol/g per min) 101 247** 109 101
UDP-GT (nmol/g per min) 892 2532** 970 924
Aromatase (pmol/g per min) 13.14 25.33** 14.21 11.53
From Kroetlinger et al., (2003)
** p < 0.01.
ALD, aldrin epoxidase; ECOD, 7-ethoxycoumarin deethylase; EH, epoxide hydrolase; EROD, 7-ethoxyresorufin
d eethylase; GST, glutathione-S-transferase; UDP-GT, uridine diphosphate glucuronosyl transferase.
A strong induction of most of the enzyme parameters (phase I and phase II) measured in the liver
tissue was detected after administration of thiacloprid at 1000 ppm (Table 41). 7-Ethoxycoumarin
deethylase was the most sensitive parameter. The metabolites thiacloprid-sulfonic acid amide and
thiacloprid-sulfonic acid Na-salt revealed no induction of the investigated liver enzymes.
Liver aromatase activity measured as the formation of tritiated water was readily detectable
in control rats. Treatment with thiacloprid at 1000 ppm approximately doubled aromatase activity in
female rat liver. This finding confirmed previous results showing strong induction of liver enzymes
including liver aromatase by thiacloprid. In contrast, metabolites of thiacloprid, thiacloprid-sulfonic
THIACLOPRID X-X JMPR 2006