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

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Hepatocytes,
hypertrophy
0 2 6 9 10 0 0 1 10 10
Average grade — 1.0 1.2 2.1 4.0 — — 1.0 1.2 2.6
Adrenals, X zone,
increased vacuolation
— — — — — 9 10 10 10 10
Grade 1 (minimal) — — — — — 3 1 — — —
Grade 2 (slight) — — — — — 6 3 — — —
Grade 3 (moderate) — — — — — — 6 6 — —
Grade 4 (marked) — — — — — — — 4 5 2
Grade 5 (massive) — — — — — — — — 5 8
Average grade — — — — — 1.7 2.5 3.4 4.5 4.8
From Wirnitzer & Rühl-Fehlert (1995)
* p < 0.05; ** p < 0.01.
Liver weights were increased in both sexes at 1250 and 6250 ppm. Histopathologically,
hypertrophy of hepatocytes was seen at doses of 250 ppm and greater in males, and of 1250 ppm and
greater in females. The adrenal weights of females were slightly (but statistically not significantly)
increased at ≥ 1250 ppm. This correlated with a dose-related increase in the severity of (fatty)
vacuolation of the female adrenal X-zone at 50 ppm and greater leading to hypertrophy of this zone
(Table 13). The X-zone is located between the zona reticularis and the adrenal medulla (function
unclear). In mice, the X-zone involutes in males at puberty and persists in females until the first
pregnancy. In non-pregnant females, it degenerates during adulthood depending on the genetic
background of the animal (Shire & Beamer, 1983). In Swiss mice, it has been shown that the
formation and degradation of this zone are influenced by pituitary and gonadal function (Deacon
et al., 1986). The ovaries appeared to have lower numbers of old corpora lutea at 1250 and 6250 ppm.
The interstitial glands of the ovaries appeared to be activated at 1250 ppm and greater. These glands
are derived mostly from atretic follicles and respond to gonadotrophin stimulation but their function
is unknown (Yuan & Foley, 2002). Kidney morphology and function were not affected in females and
at doses of up to and including 250 ppm also not in males. At 1250 and 6250 ppm a reduction or loss
of sex-specific vacuolation in the proximal tubules of kidneys was recorded in males.
The NOAEL was 50 ppm (equal to 19.9 and 27.2 mg/kg bw in males and females, respectively)
on the basis of marked vacuolation of the adrenal X zone in females at 250 ppm and greater (Wirnitzer
& Rühl-Fehlert, 1995).
Rats
In a pilot study, groups of three male and three female Wistar (Hsd/Win:WU) rats were given
thiacloprid (purity, 98.3%) at a dose of 0, 5, 10, 20, 60 or 120 mg/kg bw per day in demineralized
water with 2% v/v Cremophor EL by gavage for 14 days. The animals were regularly inspected
and weighed; the feed and water intakes were determined by groups. Medical laboratory tests were
carried out on blood and organ samples. Organs were weighed and subjected to gross pathological
and histopathological examination. In addition to normal parameters, immunotoxicity investigations
and determination of cell proliferation were also performed.
No animals died during the study. Clinical observations included reduced reactivity in males
at 120 mg/kg bw per day, and reduced production of faeces in females at 60 mg/kg bw per day and
greater. Mean body-weight gains and feed intakes were reduced in both sexes at 60 mg/kg bw per day
and greater. There were no treatment-related effects on erythrocyte parameters but the mean leukocyte
count was reduced in both sexes at 120 mg/kg bw per day. There were no treatment-related effects on
thyroid hormone levels (thyroid-stimulating hormone [TSH], triiodothyronine [T3] and thyroxin [T4]).
THIACLOPRID X-X JMPR 2006