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

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at 2000 ppm. Histopathology revealed an increased incidence of hepatic centrilobular cytomegaly
in males and females at 1000 and 2000 ppm and a statistically significant increased incidence of
ovarian stromal hyperplasia in females at 2000 ppm. There was no increase in the total number of rats
with benign or malignant tumours. An increased incidence of testicular interstitial-cell tumours and
interstitial-cell hyperplasia was seen in males at 1000 and 2000 ppm (Table 18). Testosterone concentrations
were increased in males at 2000 ppm (the only dose sampled) at 18 and 24 months.
The NOAEL for toxicity was 300 ppm, equal to 14.0 mg/kg bw per day, on the basis of reduced
body weight and liver pathology at 1000 ppm and greater. The NOAEL for tumour incidence was
300 ppm, equal to 14 mg/kg bw per day, on the basis of the increase in interstitial-cell tumours of
the testes at 1000 ppm and greater. The study claimed GLP compliance and met the requirements of
OECD test guideline 453 (Keller & Cardy, 1986).
2.4 Genotoxicity
Procymidone was not genotoxic in a range of studies in vitro and in vivo (Table 19). Many
of the studies were relatively old and contained moderate levels of detail, but the information they
contained did not indicate that procymidone has any genotoxic potential. Three more modern studies
in vitro, which complied with GLP and with the essential elements of contemporary test guidelines,
and provided negative results.
2.5 Reproductive toxicity
(a)
Multigeneration studies
Rats
Groups of 30 male and 30 female Alpk:APfSD (Wistar-derived) rats (F 0
generation) were given
diets containing procymidone (purity, > 99%) at a concentration of 0, 50, 250 and 750 ppm. The doses
Table 18. Findings in a long-term study of carcinogenicity in rats fed diets containing
procymidone
Finding
Dietary concentration (ppm)
Males
Females
0 100 300 1000 2000 0 100 300 1000 2000
Mean intake (mg/kg bw per day) 0 4.6 14 48 97 0 6 18 60 125
Body weight (g), week 81 582 572 563 535* 513* 313 297 289 278* 278*
Relative testes/ovary weight (%):
12 months 0.84 0.86 0.84 0.87 0.92 0.046 0.048 0.050 0.053 0.058
18 months 0.78 0.81 0.85 0.90 0.90 0.041 0.056 0.054 0.046 0.049
24 months 0.71 0.80 0.84 1.06* 1.04* 0.042 0.043 0.042 0.048* 0.055*
Relative liver weight (%) at
24 months
4.1 3.7 4.4 4.6 4.9* 3.2 3.4 3.6 4.1* 4.4*
Liver centrilobular cytomegaly 0 0 0 11* 17* 0 0 2 25* 36*
Testes, interstitial-cell tumour 1 1 0 10* 20* — — — — —
Interstitial-cell hyperplasia 2 0 1 7 12* — — — — —
Ovaries, stromal hyperplasia — — — — — 0 0 0 2 8*
From Keller & Cardy (1986)
* p < 0.05.
PROCYMIDONE 349–401 JMPR 2007