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

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observed incidence probably related to variability in degree of change as a result of ageing and was
not treatment-related. Chronic respiratory disease, characterized by bronchiectasis, suppurative
bronchitis and cellular infiltrates or proliferations, was evident in the lung, with a slightly higher
incidence in males at 3000 ppm compared with controls. However, this finding is common and
the incidence was variable, therefore it may not have been a result of treatment with cyromazine.
Microscopic changes in the liver were of a type and incidence common in older rats of this strain.
All the neoplastic and non-neoplastic changes observed were considered to be spontaneous
lesions, with no direct evidence of a treatment-related incidence and within the normal range of
variations.
Table 27. Incidence of selected microscopic findings in rats fed diets containing cyromazine
for 2 years
Finding
Dietary concentration (ppm)
Males
Females
0 30 300 3000 0 30 300 3000
Kidney
Chronic nephropathy 41 43 40 22 14 14 11 2
Epithelial hyperplasia 1 3 0 2 1 9 6 15
Lung
Hyperplasia 21 13 18 19 11 8 9 11
Suppurative bronchitis 16 11 13 23 9 12 6 10
Bronchiectasis 7 4 6 18 2 5 4 10
Liver
Pericholangitis 8 11 3 6 7 12 9 3
Vacuolation 0 0 0 0 1 1 0 0
Focal vacuolation: 6 2 2 2 1 1 0 0
Hepatocytomegaly 0 0 0 0 2 5 5 3
Focal hepatocytomegaly 1 2 2 2 1 5 3 5
From Blair (1982b)
In conclusion, dietary administration of cyromazine for up to 2 years resulted in decreased
body-weight gain, lower mean body weight and food consumption in male and female rats at
3000 ppm. On the basis of these effects, the NOAEL was 300 ppm, equal to 15 mg/kg bw per
day in males and 19 mg/kg bw per day in females. In females, a higher incidence (but within
the range for historical controls) of mammary gland tumours was observed at 3000 ppm (Blair,
1982b).
2.4 Genotoxicity
The mutagenic/genotoxic potential of technical cyromazine was investigated in a battery of tests
in vitro and in vivo (Table 28). All the results were negative, with the exception of an inconclusive
spot test in mice. The Meeting considered that cyromazine is not genotoxic.
CYROMAZINE X-X JMPR 2006