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

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received a macroscopic examination at necropsy. The following organs were removed and weighed:
brain, heart, liver, spleen, kidneys, adrenal glands, ovaries and testes. An extensive list of organs
and tissue were subjected to microscopic examination. Liver samples were taken from the interim
animals for enzyme determinations (10 rats of each sex at 0 and 25 ppm and five rats of each sex at
50, 500 and 1000 ppm). The concentration, stability and homogeneity of the test material in the diet
were acceptable. Mean daily intakes at 0, 25, 50, 500 and 1000 ppm were equal to 0, 1.2, 2.5, 25.2
and 51.7 mg/kg bw per day in males and 0, 1.6, 3.3, 33.5 and 69.1 mg/kg bw per day in females,
respectively.
No treatment-related clinical signs were detected by daily observation of the animals, and
mortality was not increased (Table 24). The rather low survival rate of females in the control
group compared with all treated groups was considered to be incidental but could possibly have
had an influence on certain age-related lesions. In males, the most frequent cause of death of
animals that died or were killed before the scheduled necropsy was degenerative changes in the
kidneys or heart. In females, the main causes of death were tumours in the pituitary and uterus
and to a lesser extent in the mammary gland. The increased incidence of uterine tumours at
500 ppm and greater was the main cause of death in these groups, but did not cause an overall
increase in mortality. Pituitary adenomas as death cause were markedly reduced after 500 ppm
and greater.
Thiacloprid had no effect on feed consumption at concentrations up to and including 50 ppm,
while at the highest concentration the feed consumption was slightly lower than in the controls. There
was no relevant effect on water intake. The body weights and the weight gains were not affected
at doses of up to and including 50 ppm. At 500 ppm a slight and transient growth retardation was
observed in males, while in females there was a pronounced growth retardation starting with
week 8 and reaching body-weight differences from controls of up to −15% between weeks 57 and 77.
Body-weight differences from controls at 1000 ppm were up to −12% in males and −21% in females
(Table 24).
Ophthalmological investigations gave no indication of an oculotoxic effect of the test compound
in any of the groups of males, while in females some ophthalmological findings were more frequent
in all treated groups compared with controls, e.g. lenticular alterations in the cortex/nucleus and
opacities in the retrolenticular area. Since the incidences in controls were rather low (probably as a
result of the low survival), a dose–response relationship was partly lacking and there was no increase
in the severity of changes, a treatment-related effect was not considered to be likely at doses of
up to 500 ppm. Thus, only the increased incidence of lens alterations in females at 1000 ppm was
considered to be a treatment-related effect.
Haematological investigations provided no evidence of damage to the blood, coagulation
or the blood-forming tissues. Also, urine analysis did not reveal any compound-related
effects.
The determination of plasma enzymes revealed a tendency to lower activities, especially of
aspartate aminotransferase (males and females) and alkaline phosphatase (males), essentially at the
highest dose, which was regarded as a possible secondary consequence of the liver enzyme induction.
This conclusion was corroborated by some slight changes in other parameters of liver function,
such as slightly increased cholesterol values in males and females at 1000 ppm at week 26, slightly
decreased triglyceride concentrations essentially in females at 500 and 1000 ppm (all time-points),
slightly decreased total bilirubin concentrations, essentially in males at 500 and 1000 ppm (all timepoints)
and increased total protein concentrations, essentially in males and females at 1000 ppm
(all time-points).
THIACLOPRID X-X JMPR 2006