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

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At 1500 ppm, liver APDM activity was increased and hepatic SER was increased in both
sexes at 12 and 24 months, and in females at 150 ppm at 24 months (Table 6). These changes were
considered to be adaptations, and not of toxicological significance.
Table 6. Liver aminopyrine N-demethylase activity and smooth endoplasmic reticulum
p roliferation a in rats fed diets containing cypermethrin for 2 years
Finding Sex Dietary concentration (ppm)
0 0 20 150 1500
Aminopyrine N-demethylase activity M 15.3 17.1 17.6 (8) 17.1 (4) 20.9 (7)
(μmol formaldehyde/h per g liver) F 9.8 11.0 (5) 11.4 10.9 16.1**
Smooth endoplasmic reticulum proliferation§ M 141 (7) 127 (7) 138 (7) 132 156*
F 104 (7) 119 (5) 113 (5) 135** 137**
From Milburn et al. (1982a)
F, female; M, male.
a
Means based on six observations per group unless otherwise indicated by the number in parentheses.
b
Figures represent the number of analysis points in a 320-point analysis grid coinciding with smooth endoplasmic
r eticulum.
Benign neurinomas of the heart were identified in one, one, and two male rats at 20, 150 and
1500 ppm, respectively. This type of tumour is not normally reported for Wistar rats, but given the
flat dose–response relationship over a wide range, it is unlikely that these tumours arose as a result of
treatment. Overall, there were no treatment-related neoplastic changes.
The NOAEL was 150 ppm, equivalent to 7.5 mg/kg bw per day, on the basis of clinical signs and
decreased body-weight gain at 1500 ppm, equivalent to 75 mg/kg bw per day (Milburn et al., 1982a).
2.4 Genotoxicity
A battery of tests was conducted to determine the genotoxic potential of cypermethrin in v itro and
in vivo (Table 7). The weight of evidence of the results indicated that cypermethrin is not g enotoxic.
Table 7. Results of studies of genotoxicity with cypermethrin
End-point Test object Concentration Purity (%) Results Reference
In vitro
Reverse mutation
(Ames)
S. typhimurium
TA1538; E. coli WP2 uvrA
0–500 μg/plate a NR c Negative Brooks (1976)
Reverse mutation
(Ames)
Mitotic gene
conversion
Comet assay
In vivo
Chromosomal
aberration
Host-mediated
assay
S. typhimurium
TA98, TA100, TA1535,
TA1537, TA1538
0–1000 μg/plate b NR c Negative Suzuki (1977)
S. cerevesiae NR ac NR c Negative Brooks (1976)
Human peripheral
lymphocytes
Chinese hamster
Mouse/S. cerevesiae
10, 50, 100, 200 μg/ml in
DMSO
97.1 Positive f Undeger &
Basaran (2005)
0, 20, 40 mg/kg bw per
day for 2 days orally in
DMSO d NR c Negative Dean (1977)
0, 25, 50 mg/kg bw single NR c Negative Brooks (1976)
oral dose; killed 5 h after
intraperitoneal injection of
suspension of S. cerevesiae
CYPERMETHRINS X-X JMPR 2006