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

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The NOAEL was 400 ppm, equivalent to 60 mg/kg bw per day, on the basis of reduced
body-weight gain at 1600 ppm, equivalent to 240 mg/kg bw per day. The NOAEL for carcinogenicity
was 1600 ppm, equivalent to 240 mg/kg bw per day, the highest dose tested (JECFA, 1996; Lindsay
et al., 1982).
Rats
Groups of 48 male and 48 female rats rats (96 males and 96 females were used as controls) were
maintained under specific pathogen-free (SPF) conditions and fed diets containing 1 : 1 cis : trans
cypermethrin at a concentration of 0, 1, 10, 100 and 1000 ppm for 2 years. Chemical analyses were
made confirming stability of cypermethrin in the diet over the test interval.
There was no mortality over the course of the study attributable to cypermethrin in the diet.
General health and behaviour of the cypermethrin-fed animals was not different from that of the
control animals. Body weight and food consumption data showed a reduction in dietary intake
and growth in males and females in groups fed at a dietary concentration of 1000 ppm. Gross
morphological changes were noted periodically over the course of the study. At 6 months, males
at 1000 ppm had a slightly reduced testes weight, which was not seen thereafter. Slight changes in
the gross kidney weight at periodic intervals in the study were not accompanied by notable changes
in clinical measurements or microscopic findings. The changes in kidney weight were believed
to be unrelated to the presence of cypermethrin in the diet. Liver weight increases were noted at
18 months, again in those animals maintained at the highest dose. The only clinical chemistry
change noted over the course of the study was a slight decrease in alkaline phosphatase activity in
males at 2 years. The decrease in alkaline phosphatase activity was not dose-related and was not
noted in females. Minor fluctuations were seen in various haematological parameters over the course
of the study but these, too, were not compound-related or statistically significant. These changes
are not believed to be related to the presence of cypermethrin in the diet. Gross and microscopic
examination of tissues and organs periodically over the course of the study did not suggest adverse
somatic effects.
The kidneys of most animals after 12 months showed chronic nephrosis, histologically
characterized as tubular dilatations, interstitial chronic inflammatory infiltration and glomerular
scarring. In the liver, varying degrees of chronic inflammatory infiltration, hepatocyte vacuolation
and bile-duct proliferation were observed. These changes were characteristic of ageing processes
and were not attributable to cypermethrin. Dermal ulceration was present in a number of animals
over the course of the study. A portion of the sciatic nerve from 12 animals fed cypermethrin at
1000 ppm for 1 year and 12 animals in the control group was histologically examined for signs
of neurotoxicity. There were no differences in the incidence of abnormal fibres in the controls and
animals fed cypermethrin for 12 months (Trigg et al., 1977). Microscopic examination of the sciatic
nerve from animals sacrificed at the conclusion of the study showed a small number of nerve fibres
exhibiting slight Wallerian degeneration changes. These degenerative changes increased with age,
but did not appear to be dose-related with respect to severity. Thus, cypermethrin did not induce
neuropathy clinically nor did it induce histological evidence of nerve degeneration. There did not
appear to be a significant increase in the incidence of tumour formation in either males or females
over the course of the study. A large number of pituitary adenomas were reported predominantly in
females at all doses including controls. This occurrence did not appear to be dose-related as similar
events were recorded at all doses.
The NOAEL for toxicity was 100 ppm, equivalent to 5 mg/kg bw per day, on the basis of
reduced body weights in both sexes at 1000 ppm, equivalent to 50 mg/kg bw per day. The NOAEL for
carcinogenicity was 1000 ppm, equivalent to 50 mg/kg bw per day, the highest concentration tested
(Annex 1, reference 33; McAusland et al., 1978).
CYPERMETHRINS X-X JMPR 2006