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

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Table 17. Relevant findings in a 4-week study in rats exposed to thiacloprid by inhalation
Finding Dose (mg/m 3 )
Males
Females
0 2 18.2 143.4 0 2 18.2 143.4
Body weight (g):
Day 4 242 240 237 217** 166 166 167 151**
Day 28 295 287 292 290 187 186 189 192
Cholesterol (mmol/l) 1.70 1.68 1.64 1.86 1.62 1.65 1.74 2.12**
AP (U/l) 295 292 310 339 189 206 198 226*
Bile acids (μmol/l) 23.0 25.3 27.4 25.2 29.8 21.4 20.1 42.6*
N-DEM (mU/g) 122 135 149* 176** 67 52* 65 144**
O-DEM (mU/g) 9.8 11.1 11.4 18.5** 8.8 8.3 8.5 18.0**
P 450 (nmol/g) 41.8 41.6 44.6 57.4** 34.3 33.5 36.6 53.6**
Liver weight (g) 11.06 10.87 11.01 12.21 7.19 7.10 7.22 8.40**
Relative liver weight (g/100g) 3.75 3.79 3.78 4.21** 3.90 3.86 3.86 4.44**
Thyroid weight (mg) 6.2 7.1 9.6 8.5 5.8 4.9 5.9 7.7
Relative thyroid weight (mg/100g) 2.1 2.5 3.3 2.9 3.1 2.7 3.1 4.0
Liver, hepatocyte hypertrophy 0 0 5 7 0 0 0 4
Thyroid, follicular epithelium hypertrophy. 0 0 0 2 0 0 0 0
From Pauluhn (1998)
* p < 0.05; ** p < 0.01
AP, alkaline phosphatase; O-DEM, O-demethylase; N-DEM, N-demethylase.
There were no treatment-related macroscopic findings at necropsy. The main organ weight
changes are presented in Table 17. The increased lung weights in males lacked a dose–response
relationship and there was no compound-induced effect on female lung weight. Therefore, the
lung-weight changes in males were considered to be incidental. The thyroid weights of males were
slightly increased at 18.2 mg/m³ and 143.4 mg/m³ (not in a dose-dependent amnner).
The microscopic examination revealed minimal to slight hypertrophy of hepatocytes at
≥ 18.2 mg/m³ air in males and at 143.4 mg/m³ in females. Slight hypertrophy was observed in
the thyroidal follicular epithelium of two males at 143.4 mg/m³. Microscopy did not detect any
treatment-related findings in the respiratory tract.
The NOAEC was 18.2 mg/m³ (0.018 mg/l air) on the basis of clinical signs, reduced body
weights, liver toxicity in females (increased plasma concentrations of cholesterol, alkaline phosphatase
and bile acids) and thyroid effects in males (increased weight, hypertrophy of follicular epithelium)
at 143.4 mg/m³ (Pauluhn, 1998).
In a short-term study of dermal toxicity, groups of five male and five female Wistar (Hsd
Cpb:WU) rats were given thiacloprid (purity, 97.2 %) at a dose of 0, 100, 300 or 1000 mg/kg
bw per day by dermal application. The animals were exposed for 6 h per day and received 22
applications for 28 days. Additionally, satellite groups of five males and five females were given a
dose at 0 or 1000 mg/kg bw per day followed by a 2 week recovery period. The test substance
was applied undiluted and moistened with water immediately before application. After exposure,
the dressings were removed and the application sites were cleaned with soap and water. The
study was performed in compliance with test guideline OECD 410. Dose selection was based
on a 3-week dose range-finding study using doses of 0 and 1000 mg/kg bw per day. The effects
reported in this study included lower feed intake, leukocyte changes, increased cholesterol levels,
THIACLOPRID X-X JMPR 2006