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

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Groups of four male and four female beagle dogs received capsules containing procymidone
technical (purity, 98.5%) once daily at a dose of 0 (empty capsule), 20, 100 or 500 mg/kg bw per
day for 1 year. All dogs were observed twice per day for mortality, moribundity and clinical signs of
toxicity and were given a detailed physical examination weekly. Body weight and food consumption
were recorded weekly. Ophthalmoscopic assessments were made during weeks 26 and 52. Clinical
pathology and haematology parameters were measured in blood sampled before dosing began
and during weeks 13, 26, 39 and 52. All dogs were given a gross postmortem examination, selected
organs were weighed and tissues were examined microscopically.
One male in the group at 100 mg/kg bw per day was killed following an irreparable intussusception
of the large intestine in week 19. Emesis and soft faeces were observed in dogs in all groups,
including the controls, but appeared to be more prevalent at 500 mg/kg bw per day; the incidence
of diarrhoea/soft faeces in males at this, the highest dose, was statistically significantly increased
relative to values for the controls (p = 0.02, Mann-Whitney U test subsequent to a Kruskal-Wallis
ANOVA). Dogs in the groups receiving procymidone generally consumed more food and put on
more weight than did the controls. There was an increase in serum globulin concentration in weeks
39 and 52 amongst male dogs at 500 mg/kg bw per day, resulting in a reduced albumin : globulin
ratio; a less marked effect was present at 100 mg/kg bw per day. Serum ALP activity was increased in
males at the highest dose (Table 16). Serum concentrations of creatinine, glucose, BUN and calcium
were similar between groups. No treatment-related changes were detected on organ weights or by
gross or microscopic pathology examination.
Table 15. Findings in dogs (n = 6) fed capsules containing procymidone for 26 weeks
Finding
Dose (mg/kg bw per day)
0 20 100 500
M F M F M F M F
ALP activity (U/l) 149 143 164 133 160 142 196 242
BUN (mg/dl) 18 21 20* 21 20 20 21* 23
Glucose (mg/dl) 92 94 93 95 94 94 102* 89
Calcium (mg/dl)
(before dosing)
11.1
(11.1)
11.3
(11.2)
11.3
(11.0)
11.5
(11.2)
11.4*
(11.2)
11.4
(11.3)
11.5*
(11.2)
11.3
(11.4)
Heart weight (g) 103 93 99 83 100 97 102 85
Relative heart weight (%) 0.83 0.88 0.79 0.74* 0.78 0.86 0.83 0.76*
From Nakashima et al. (1984)
ALP, alkaline phosphatase; BUN, blood urea nitrogen; F, females; M, males.
* p < 0.05.
Table 16. Findings in dogs (n = 4) fed capsules containing procymidone for 52 weeks
Finding
Dose (mg/kg bw per day)
0 20 100 500
Males Females Males Females Males Females Males Females
Alkaline phosphastase activity (U/l) 27 40 31 46 29 34 53* 44
Total protein (g/dl) 5.8 5.8 5.8 5.6 6.6* 6.1 6.6* 6.1
Globulin (g/dl) 2.4 2.3 2.3 2.1 2.9 2.5 3.2* 2.3
Albumin : globulin ratio 1.5 1.6 1.5 1.6 1.3 1.5 1.1 1.6
From Dalgard & Machotka (1992)
* p < 0.05.
PROCYMIDONE 349–401 JMPR 2007