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

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Dogs
Groups of four male and four female beagle dogs were given diets containing diazinon (purity,
87.7%) at a concentration of 0, 0.1, 0.5, 150 or 300 ppm (equal to 0.0034, 0.02, 5.9, or 10.9 mg/kg bw per
day) for 90 days. No treatment-related mortalities occurred. The treatment did not adversely affect food
consumption, ophthalmoscopy, haematology, urine analysis, organ weights or macroscopic findings.
Clinical signs such as emesis or bloody faeces were sporadically observed in males at 300 ppm
and in females at 150 ppm. Reduced body-weight gain was observed in females at 150 ppm and at
300 ppm in both sexes. In males, inhibition of serum cholinesterase activity was observed resulting in
activities of 70%, 20% and 15% of that measured in control rats at the end of the study at 0.5, 150 and
300 ppm, respectively. Erythrocytes activities corresponding to 75% and 69% of control activity were
measured at 150 ppm and 300 ppm, while in brain acetylcholinesterase activity was 69% and 58% of
control activity at 150 and 300 ppm, respectively. In females a reduction in acetylcholinesterase activity
was observed at 150 and 300 ppm. Serum and erythrocyte cholinesterase activities were about 18%
and 70% of control activity, respectively, at both doses, and brain cholinesterase activity was 70% and
55% that of control activity at 150 and 300 ppm, respectively. Other changes in biochemical parameters
consisted of a decrease in total protein at 300 ppm in males. The only microscopic alteration that might
have been compound-related was atrophy of the pancreatic acini in one male dog at the highest dose.
The NOAEL was 0.5 ppm (equal to 0.02 mg/kg bw per day) on the basis of inhibition of erythrocyte
and brain cholinesterase activity at dietary concentrations of 150 ppm and above (Barnes et al., 1988;
Annex 1, reference 70, modified with reference to the original data).
In a study of oral toxicity, Groups of four male and four female beagle dogs) were fed diets
containing diazinon (purity, 87.7%) at a concentration of 0, 0.1, 0.5, 150 or 300 ppm (equal to 0.0032,
0.015, 4.7, or 7.7 mg/kg bw per day for males and 0.0037, 0.02, 4.5, or 9.1 mg/kg bw per day for females)
for 52 weeks. Owing to lack of body-weight gain, the dietary concentration of 300 ppm was reduced
to 225 ppm after 14 weeks of treatment. Mortality was not increased by treatment and haematology,
urine analysis, gross pathology and histopathology revealed no changes attributable to treatment. Overt
clinical signs of dehydration and emaciation became evident in one male at 300/225 ppm. The symptoms
remained although the initial dose was reduced. Reductions in body-weight gain were observed at
150 ppm and higher in males and at 300/225 ppm in females. However, no clear-cut dose–response
relationship was evident and the differences attained statistical significance relative to the control group
only at certain observation times. Food consumption was reduced at dietary concentrations of
150 ppm and higher, again without a clear dose–response relationship, most probably owing to reduced
palatability of the feed admixtures. Treatment-related decreases in acetylcholinesterase activity at doses
of 0.5 ppm and higher were found: serum cholinesterase activity was reduced at 0.5 ppm and higher
in males and at 150 ppm and higher in females, resulting in activities that were about 20% of that in
the control group at 150 and 300/225 ppm in both sexes. Erythrocyte cholinesterase activity was also
reduced at 150 and 300/225 ppm, activities corresponding to about 70% of the control activity being
measured in both sexes. Brain cholinesterase activity was inhibited to 75% of that of controls in females
at 150 ppm, and at 300/225 ppm to 65% and 75% of that of controls in females and males, respectively.
The NOAEL was 0.5 ppm (equal to 0.02 mg/kg bw per day) on the basis of inhibition of erythrocyte
and brain cholinesterase activity at 150 ppm and above (Rudzki et al., 1991; Annex 1, reference 70,
modified with reference to the original data).
1.3 Long-term studies of toxicity
Rats
Groups of 30 male and 30 female Sprague-Dawley (Crl:VAF/Plus CD[SD]Br) rats (40 males
and 40 females in the control group and at 250 ppm) were fed diets containing diazinon (purity,
DIAZINON X-X JMPR 2006