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

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4.2 Short-term studies of toxicity
Mice
Groups of eight male and eight female CD-1 mice received diets containing alpha-cypermethrin
(purity, 95.4%) at a concentration of 0, 200, 400, 800, 1200 or 1600 mg per kg feed for 29 days,
respectively equal to 0, 27, 56, 121, 166 and 241 mg/kg bw per day for males, and 0, 34, 73, 146,
212, and 294 mg/kg bw per day for females. One male at 1600 mg/kg and one female at 1200 mg/kg
were killed in a moribund condition. These animals showed neurological disturbances. Mice at 1200
and 1600 mg/kg developed ungroomed coats, ataxia/abnormal gait, over-activity or hunched posture.
At 800 mg/kg, some animals had ungroomed coats and abnormal gait. Body-weight gain was doserelatedly
decreased in mice at 1200 and 1600 mg/kg and in females at 800 mg/kg. A similar, but less
marked effect was apparent in males receiving 800 mg/kg and females receiving 400 mg/kg. Food
consumption was lowered in rats at 1200 and 1600 mg/kg during the first 2 weeks. A depression in
lymphocyte numbers was noted in males at 1600 mg/kg. ALT and aspartate aminotransferase (AST)
activities were increased in males at 1600 mg/kg. Urea concentrations were increased in all dosed
males and females, without a clear dose–response relationship. Plasma albumin and abumin/globulin
ratio were decreased in males at 1600 mg/kg. Relative kidney weight was increased in males at 800,
1200 and 1600 mg/kg. Relative lung weight was increased in males at 1600 mg/kg. No macroscopic
or microscopic effects were seen. No effects were seen at 400 mg/kg feed, equal to 56 mg/kg bw per
day (JECFA, 1996; Green, 1993).
Groups of 12 male and 12 female CD-1 mice received diets containing alpha-cypermethrin
(purity, 95.4%) at a concentration of 0, 50, 250 or 1000 mg per kg feed for 13 weeks, equal to 0, 6.3,
33 and 170 mg/kg bw per day for males, and 0, 7.4, 36 and 185 mg/kg bw per day for females. Four
males at 1000 mg/kg died during week 12, probably due to stress of treatment and refusal of food and
water. The relative kidney weights of these animals appeared to be slightly increased. One mouse at
250 mg/kg died. Clinical signs included thin build, ungroomed coat, hair loss and encrustations of
the dorsal body surface in animals receiving 1000 mg/kg, ungroomed haircoat in mice at 250 mg/kg,
hair loss and encrustations in males at 250 mg/kg and hair loss in two males at 50 mg/kg, and three
males in the control group. Body-weight gain was markedly lower in mice at 1000 mg/kg and lower
in mice at 250 mg/kg. Food consumption was slightly higher in mice at 1000 mg/kg. Overall food
conversion efficiency of animals at 1000 mg/kg (and to a lesser extent, at 250 mg/kg) was lower than
that of controls. In males at 1000 mg/kg, erythrocyte volume fraction, haemoglobin, erythrocyte, total
leukocyte and lymphocyte counts were decreased. AST activity was increased in a dose-dependent
manner in males at 250 and 1000 mg/kg, and glucose was decreased in males at 1000 mg/kg. Serum
alkaline phosphatase activity was increased in females at 1000 mg/kg. Urinary specific gravity was
increased in mice at the highest dose. In males at 1000 mg/kg, relative brain, adrenal, heart, kidney,
liver, spleen, lung and testes weights were increased. In females, relative liver weight was increased at
250 and 1000 mg/kg and relative brain and spleen weight at 1000 mg/kg. Two males and 11 females at
1000 mg/kg were considered to be emaciated at necropsy. No histological changes were observed.
The NOAEL was 50 mg/kg feed, equal to 6.3 mg/kg bw per day, on the basis of one death,
clinical signs, reduced body-weight gain and decreased food conversion efficiency, and increased
AST activity in males at 250 mg/kg feed, equal to 33 mg/kg bw per day (JECFA, 1996; modified with
reference to the original report of Amyes et al., 1994).
Rats
Groups of 10 male and 10 female Wistar were fed diets containing alpha-cypermethrin (purity,
96.5%) at a concentration of 0 (20 rats of each sex), 20, 100, 200, 400 or 800 mg per kg feed
CYPERMETHRINS X-X JMPR 2006