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

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At the highest dose, clotting time (hepatoquick) was decreased, protein levels were
increased in males, and hepatic N-/O-demethylases, cytochrome P450, and liver triglycerides
were significantly increased on day 7. Bile-acid concentrations and to a minor extent glutamate
dehydrogenase activities were decreased, and hepatic N-/O-demethylases were statistically
significantly increased in females on day 7. No biochemical changes were evident at the terminal
sacrifice.
Gross necropsy revealed dark spleens at 19 mg/m³ (four females) and 205 mg/m³ (four females)
at the interim necropsy. Dark spleens were not observed in any animals at the terminal necropsy.
At 205 mg/m³, liver size and weight were increased, and thymus size and weight were reduced in
males at the interim sacrifice. There were no treatment-related macroscopic findings or organ weight
changes in any animals at the terminal sacrifice.
The no-observed-adverse-effect concentration (NOAEC) was 19 mg/m³ (0.019 mg/l air) for
both sexes on the basis of clinical signs, reduced body weight, liver effects (increased weight, enzyme
induction) and decreased thymus weights at 205 mg/m³. All effects had resolved by the end of the
recovery period (Pauluhn, 1995).
In a study on toxicity by inhalation, groups of 10 male and 10 female Wistar (Hsd Win:WU)
rats were exposed (nose only) to aerosolized thiacloprid (purity, 97.2%) at analytical concentrations
of 0, 2.0, 18.2 or 143.4 mg/m³ air under dynamic conditions for 6 h per day on 5 days per week for
4 weeks. The group at the highest dose was initially exposed to a target concentration of 200 mg/m³
which led to marked respiratory distress and reduced body-weight gain so that it was reduced
to 100 mg/m³ from the second week on. The study was performed in compliance with test
guideline OECD 412. For all treatment groups, the MMAD of the particles was approximately
2.9 μm with a GSD of 1.8. Between 51–55% of aerosol mass was less than 3 μm.
Clinical observations, body weight and feed intake were recorded at suitable time-points.
Reflexes and the rectal temperatures were evaluated during the course of the study. Ophthalmological
examinations were performed before the start of the study and towards the end. Urine analysis was
also performed near to the end of the study. All the animals were given a macroscopic examination
at necropsy. Selected organs were removed and weighed, and blood was sampled for haematological
and biochemical determinations. Histopathology of retained organs and tissues was performed in this
study.
No deaths occurred during the study. Clinical signs were observed at the highest dose and
included bradypnea, reduced motility, tremor, laboured breathing pattern, piloerection, ungroomed
hair-coat, atony, rales, salivation, mydriasis, miosis and vocalization. These signs were considered
to be a consequence of respiratory distress rather than as central nervous effects. Reduced body
weights (days 4–11) and hypothermia were evident in both sexes at the highest dose. No treatmentrelated
effects were revealed by the ophthalmological examinations.
Erythrocyte parameters were not affected by treatment. There were significant increases
in the concentrations of phosphate, glucose, cholesterol, bile acids and calcium and increased
alkaline phosphatase activity in females at the highest dose. Glucose and phosphate concentrations
were significantly increased in males at the highest dose. Liver enzyme induction was detected
at 143.4 mg/m³ air and was more pronounced in females than in males. A marginal effect in
some enzymes was also seen at 18.2 mg/m³ (Table 17). Changes indicative of an effect on the
thyroid were not seen during this study. Urine analysis did not reveal any treatment-related
effects.
THIACLOPRID X-X JMPR 2006