Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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daily for signs of toxicity; body weight was measured two or three times during the first 2 weeks
of treatment and then weekly; food consumption was also measured weekly. Urine analysis was
conducted after 3, 6 and 9 months of treatment; haematological and blood chemistry examinations
were made at 6 and 9 months. A complete necropsy was conducted on each rat at termination, organ
weights were recorded and tissues were examined by histopathology.
Achieved intakes of procymidone were not calculated. No compound-related effects were
observed on mortality, clinical signs, food and water consumption, urine analysis and clinical chemistry.
Depression of body-weight gain was observed in males and females at 1500 ppm. There were
slight decreases (< 10%) in packed cell volume (PCV; haematocrit) and haemoglobin values in males
and females at 1500 ppm for 6 months, but not in those fed the same dose for 9 months. Serum ALT
activity was increased at ≥ 500 ppm after 6 months but not after 9 months. Liver-weight to bodyweight
ratio was increased after 6 months at 1500 ppm in males and at 500 (< 10%) and 1500 ppm
in females (Table 14), but this was reversible and had returned to normal in males after the 3-month
recovery period. The spleen to body-weight ratio was also increased in male rats at 500 and 1500 ppm
at 6 months; however, this increase was not apparent after treatment for 9 months and was therefore
considered not related to treatment (Table 14). Relative adrenal weight was significantly increased
at 1500 ppm in males and 500 and 1500 ppm in females, and relative pituitary weight at all doses
in females after 6 months, but with no dose–response relationship; there were no histopathological
changes in these organs and therefore alterations in weight were considered to be of no toxicological
significance. After 9 months, absolute and relative testes weights were increased. The only histopathological
lesion that could be attributed to treatment with procymidone was swelling and vacuolar
degeneration of the liver cells in males fed 1500 ppm for 6 and 9 months. All the findings showed
clear evidence of returning to normal after the recovery period.
Table 14. Findings in rats fed diets containing procymidone for 13 weeks
Finding
Dietary concentration (ppm)
0 150 500 1500
M F M F M F M F
Body weight (g) at 6 months) 669 349 687 337 672 327 632 306*
ALT activity (U/l):
6 months 15 18 17 19 21* 23 21 23
9 months 33 42 — — — — 26 23
Relative liver weight (%):
6 months 2.8 3.0 2.9 2.8 2.9 3.2* 3.2* 3.3*
9 months 2.9 2.8 — — — — 3.3* 3.4*
Recovery 2.9 2.8 — — — — 2.8 3.0*
Relative testes weight (%):
6 months 0.55 — 0.56 — 0.54 — 0.59 —
9 months 0.42 — — — — — 0.58* —
Recovery 0.42 — — — — — 0.49 —
Relative spleen weight (%)
6 months 0.12 0.14 0.13 0.14 0.13 0.16* 0.13 0.18*
9 months 0.12 0.16 — — — — 0.13 0.16
From Fujita et al. (1976) and Hosokawa (1984)
ALT, alanine aminotransferase; F, females; M, males.
* p < 0.05.
PROCYMIDONE 349–401 JMPR 2007