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

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Table 27. Dosing schedule and termination times in a study of serum hormone concentrations in
rats given diets containing procymidone
Parameter Experiment 1 Experiment 2 Experiment 3
Dietary concentrations
(ppm)
700, 2000, 6000 100, 300, 700 and 2000 6000
Duration Up to 3 months Up to 6 months One month
Termination times
Fourteen days, 1 month and
3 months after the start of
treatment
One, 3 and 6 months after
the start of treatment
One month after the start of
treatment, then 2 weeks, 1, 3 and
6 months after treatment
From Murakami et al (1986)
and significant manner at 700 ppm and greater; LH concentrations were significantly increased at
6000 ppm. In the second experiment, serum testosterone concentrations were increased at 700, and
2000 ppm. Serum concentrations of testosterone and LH returned to normal after 1 month of the
recovery period. Serum estradiol concentrations were close to the limit of detection in all groups.
In the positive-control group, administration of cadmium chloride produced a reduction in testes,
seminal vesicle, epididymes and prostate weights, an increase in LH concentration and a decrease
in testosterone indicating a different mechanism of action from procymidone. The NOAEL for hormonal
effects was 300 ppm, equivalent to 30 mg/kg bw per day. The report was checked by a quality
assurance unit (Murakami et al, 1986).
Tests for testicular function
Rodents
Groups of 30 male ICR mice received diets containing procymidone (purity, > 99.3%) at a
concentration of 0, 1000, 5000 or 10 000 ppm for up to 13 weeks. Groups of 12 male Sprague-
Dawley rats received diets containing procymidone at a concentration of 0, 700, 2000 or 6000 ppm
for 13 weeks. Routine examinations were performed during the study. Rodents were terminated after
2, 4 and 13 weeks of treatment. Body weights and food consumption were recorded weekly. At termination,
reproductive organs were removed and weighed. Concentrations of testosterone were determined
in serum and testes and LH was determined in serum and pituitary. The testicular response
to stimulation by human chorionic gonadotrophin (hCG) and the binding of hCG to the LH/hCG
receptor in testes were determined in vitro.
In mice, mean achieved intakes over 13 weeks were 133, 638 and 1338 mg/kg bw per day. There
was no consistent effect on body weight, food consumption or organ weights. Testosterone concentrations
were elevated in serum (165%) and testes (248%) after 2 weeks of treatment at 10 000 ppm
and levels returned to normal at 4 and 13 weeks. LH concentrations in serum and pituitary were
elevated for the first 4 weeks at 1000 ppm and greater; returning to normal thereafter. There was
a slight increase in hCG-stimulated testosterone production at 10 000 ppm after 2 weeks but this
returned to control levels after 3 months. The binding affinity of hCG decreased in mice at 5000 and/
or 10 000 ppm during the 3-month treatment period.
In rats, mean achieved intakes over 13 weeks were 47, 132 and 388 mg/kg bw per day. There
was no consistent effect on body weight or food consumption. Seminal vesicle weight was decreased
and testis weight increased at 6000 ppm after 2 weeks. An increase in testis weight was also apparent
at all doses (approximately 10%, but no dose–response relationship) after 4 weeks and at 6000 ppm
after 13 weeks (10%). In rats at 6000 ppm, testosterone concentrations in serum were increased
(155%) throughout the experimental period and increases were noted in testes after 4 weeks (220%)
and 13 weeks (160%). LH concentrations were only elevated in serum for the first 4 weeks at 6000 ppm
(300%). In the pituitary, LH concentrations were elevated at all doses after 4 weeks (138–180%)
PROCYMIDONE 349–401 JMPR 2007