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

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reduced triglyceride concentrations, increased liver weight, lower thymus weights and dark-red
spleens.
Clinical observations, body weight and feed intake were recorded at suitable time-points.
The treated skin sites were examined daily and any reactions were scored on the Draize scale. All
the animals were given a macroscopic examination at necropsy. Blood samples were taken for
haematological and biochemical determinations. The following organs were removed and weighed:
brain, heart, lungs, liver, spleen, kidneys, adrenals, thymus and testes. Histopathology of retained
organs and tissues was carried out.
No animals died during the study or showed clinical signs of toxicity. There were no
treatment-related effects on body weight. No local skin reactions were observed at the treatment
sites. In females, there was a transient decrease in feed intake at 1000 mg/kg bw per day. The
haematological and clinical chemistry examinations did not reveal any treatment-related changes.
There were no treatment-related macroscopic findings at necropsy. The mean liver weights (absolute
and relative) were increased in both sexes at 1000 mg/kg bw per day (Table 18). At the end of the
recovery period, the liver weights of the group at 1000 mg/kg bw per day were comparable to control
values. Microscopy revealed centrilobular hypertrophy in combination with a more homogeneously
structured cytoplasm in male livers at doses of ≥ 300 mg/kg bw per day and in females at 1000 mg/kg
bw per day. These findings were considered to be a consequence of liver enzyme induction. At the end
of the recovery period, these changes were still evident in two out of five males but not in females.
The thyroids of males and females displayed follicular cell hypertrophy at 1000 mg/kg bw. This effect
was reversible in females, but not completely reversible in males within the 2-week recovery period
(one out of five males still exhibited the effect). There were no treatment-related microscopic skin
findings at the treatment sites.
Table 18. Relevant findings in a 4-week study of dermal toxicity in rats given thiacloprid by
d ermal application
Finding
Dose (mg/kg bw per day)
Males
Females
0 100 300 1000 0 100 300 1000
Body weight (g) 306 299 286 296 218 221 217 221
Liver weight (g) 12.65 12.7 12.23 14.26 8.70 8.87 9.12 9.88**
Liver weight, relative (g/100g) 4.10 4.25 4.26 4.81** 3.99 4.01 4.21 4.47*
Liver, hepatocyte hypertrophy 0 1 3 5 0 0 0 3
Thyroid, follicular. epithelium hypertrophy. 0 0 0 3 0 0 0 2
Recovery groups
Body weight (g) 336 — — 321 231 — — 230
Liver weight (g) 13.45 — — 12.84 8.97 — — 9.14
Relative weight (g/100g) 4.01 — — 4.00 3.89 — — 3.97
Liver, hepatocyte hypertrophy 0 — — 2 0 — — 0
Thyroid, follicular. epithelium hypertrophy 0 — — 1 0 — — 0
From Kroetlinger & Sander (1997)
* p < 0.05; ** p < 0.01
The NOAEL for systemic toxicity was 300 mg/kg bw per day in males and females on the
basis of thyroid follicular cell hypertrophy at 1000 mg/kg bw per day. Hypertrophy of hepatocytes
and thyroid follicular cells in males at 1000 mg/kg bw per day was partially reversible after a 2-week
recovery period. The NOAEL for skin reactions was 1000 mg/kg bw per day, the highest dose tested
(Kroetlinger, 1997b).
THIACLOPRID X-X JMPR 2006