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

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Dogs
In a dose range-finding study, groups of two male and two female beagle dogs were given diets
containing thiacloprid (purity, 98.6%) at a concentration of 0, 100, 300, or 1000 ppm for up to
10 weeks. Since no clinical signs and no other effects were seen, the highest dose was increased from
1000 to 1250 ppm from day 19 of treatment onwards, and, as no effects occurred, to 1600 ppm from
day 26 of treatment onwards. This dose was further increased to 2500 ppm on day 38. This dose was
administered until the end of the study. A satellite group of two male and two females was given a
dietary concentration of 2500 ppm from the beginning of the study for 4 weeks. The doses in study
week 9 were equal to average doses of 0, 3.3, 9.6, 80.0 and 65.7 mg/kg bw per day (satellite group)
for both sexes.
In the group at 1000 ppm, a slight reduction in feed intake and body-weight gain was observed,
starting after the dose increase with week 4, while after a 4-week administration of 2500 ppm to a
separate group of dogs, reduced feed intakes and reduced body-weight gains were detected. Other
symptoms were not observed. In the groups at 1000 and 2500 ppm, slightly increased urea and
creatinine concentrations were detected. In males treated with thiacloprid at 2500 ppm from the
beginning of the study, slightly increased alanine transferase activity was seen which was partly
reversible during the study period. Slight changes in the thyroid hormones were observed: T4 was
slightly reduced and T3 and thyroxin-binding capacity were slightly increased in females at 2500 ppm
at study initiation. Marginally increased activities of liver enzymes, ECOD and EH and, in females
only, of GST were seen in the animals treated at 2500 ppm at study initiation. Urine analysis did not
reveal any changes. No gross findings were detected. Increased prostate weights were found in males
at 1000 and 2500 ppm. Histopathologically, slight cytoplasmic changes in the liver were detected in
one male and one female treated at 2500 ppm for 4 weeks from study initiation, and in one female
treated initially with a dose of 1000 ppm which was gradually increased to 2500 ppm.
The NOAEL was 300 ppm, equal to 9.6 mg/kg bw, on the basis of reduced feed intake, increased
urea and creatinine concentrations and increased prostate weights at 1000 ppm and greater (Wetzig & Geiss,
1998a).
Groups of four male and four female beagle dogs were given diets containing thiacloprid,
(purity, 96.8–97.2 %) at a concentration of 0, 250, 1000 or 2000 ppm for 15 weeks. The animals at
the highest dose were treated initially with a dose of 4000 ppm from day 1 to day 4, which caused
severe clinical signs, like vomitus and body-weight reduction. Therefore, after a period without
treatment from day 5 to day 14, this group was treated at 2000 ppm from day 15 onwards. This
period was compensated for by a 2-week extension of the study period. The study was performed
in compliance with test guideline OECD 409. The concentration, stability and homogeneity of the
test material in the diet were acceptable. Daily intakes were equal to 0, 8.5, 34.9 and 68.0 mg/kg
bw per day in males and 0, 8.9, 34.7 and 65.3 mg/kg bw per day in females, at 0, 250, 1000 and
2000 ppm, respectively.
Within the first days of treatment, animals at the highest dose (4000 ppm) displayed clinical signs,
including vomitus, slight tremor, reduced or no feed intake, and body-weight decrease. Therefore,
the treatment with the highest dose was stopped on day 4, and the dose was reduced to 2000 ppm.
During the further course of the study, no clinical signs or effects on feed intake and body-weight
development were observed. The lack of clinical signs at the chosen doses was not the consequence
of poor absorption as was demonstrated by plasma concentrations determinations in study week 14.
Blood samples were taken 0, 2, 4, 6 and 24 h after feeding. The peak values as measured 4–6 h after
administration were approximately 2, 6, and 14 μg/ml for dogs at 250 ppm, 1000 ppm and 2000 ppm,
respectively. Compared with the administered doses the blood concentrations are regarded as very
high, thus, indicating a high absorption rate.
THIACLOPRID X-X JMPR 2006