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

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they may also be related to variation and small sample size. The cell proliferation assays revealed
increased cell proliferation in the perivenular region of the liver in females at 120 mg/kg bw per day.
A reduction in cell proliferation, particularly in the renal medulla, and to a lesser extent in the renal
cortex, was reported in females at 120 mg/kg bw per day.
Mean thymus weights (absolute) were reduced at ≥ 60 mg/kg bw per day. The mean relative
liver weights of males and females were increased at ≥ 60 mg/kg bw per day, while mean absolute
liver weight were increased in both sexes at 120 mg/kg bw per day. These liver weight changes
correlated histopathologically with a slightly atypical structure of the hepatocellular cytoplasm
(≥ 60 mg/kg bw per day in females, 120 mg/kg bw per day in males) and slight hepatocytic
hypertrophy at 120 mg/kg bw per day in both sexes. Microscopy also revealed an increased mitotic
rate in the thyroids of male rats at 120 mg/kg bw per day.
The NOAEL was 20 mg/kg bw per day on the basis of reduced body-weight gain and reduced
feed intake at 60 mg/kg bw per day and greater (Kroetlinger, 1995a).
Groups of five male and five female Wistar (Hsd/Win:WU) rats were fed diets containing
thiacloprid (purity, 98.6%) at a concentration of 0, 25, 100, 500 or 2000 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. Clinical chemistry tests were carried out after 7 days and at the end of treatment. All
the animals were examined macroscopically at termination. The liver and thyroid were removed
and weighed, and subjected to gross and histopathological examinations. 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, 2.5, 11.2, 49.2 and 187.6 mg/kg
bw per day in males, and 0, 2.3, 9.6, 49.5 and 187.2 mg/kg bw per day in females, at of 0, 25, 100,
500 and 2000 ppm, respectively.
No deaths occurred during the study. Constipation was evident on day 1 in one out of five females
at 500 ppm and three out of five males and four out of five females at 2000 ppm. Significant reductions
in mean body weight were seen in both sexes at 2000 ppm and small reductions were seen in females
at 500 ppm. Feed consumption was significantly reduced during week 1 at 2000 ppm. Water intake was
increased in females at 2000 ppm during week 2. Cholesterol levels were significantly increased in
males at 100 ppm and greater and in females at 2000 ppm on day 7, while after 14 days of treatment,
cholesterol levels were increased in both sexes at the highest dose only. There was a significant increase
in TSH in females on day 14 at 2000 ppm. No treatment-related effects were seen on the levels of T3
and T4 or thyroxin-binding capacity. Liver enzymes (7-ethoxycoumarin deethylase [ECOD], aldrin
epoxidase [ALD], epoxide hydrolase [EH], glutathione-S-transferase [GST], uridine diphosphate
glucuronosyl transferase [UDP-GT]) were induced in both sexes at 500 ppm and greater (Table 15).
Table 15. Main findings of a 14-day study in rats fed diets containing thiacloprid
Finding
Dietary concentration (ppm)
Males
Females
0 25 100 500 2000 0 25 100 500 2000
Body weight (g):
Day 0 101 103 105 104 103 98 105 101 95 105
Day 7 148 148 151 139 115** 133 134 128 118* 111**
Day 14 196 196 194 184 147** 155 154 151 138 132**
GGT (U/l) 0 0 0 0 2* 0 0 0 0 2*
Cholesterol (mmol/l) 2.23 2.46 2.60 2.63 3.22** 2.17 2.28 2.39 2.43 3.37**
THIACLOPRID X-X JMPR 2006