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

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Table 2. Histopathological findings in dogs fed capsules containing profenofos for 1 year
Finding Severity No. of dogs affected (n = 4) a
Kidney
Deposition of bile
pigment
Liver
Increase in
binucleated
h epatocytes
Hyperplasia of
bile duct
Dose (mg/kg bw per day)
Males
Females
0 0.015 0.05 1.0 12.5 0 0.015 0.05 1.0 12.5
Grade 1 1 3 1 1 1 2 0 2 2 2
Grade 2 1 0 1 1 1 0 2 0 0 1
Grade 3 0 0 0 0 3 0 0 0 0 0
Total b 2 3 2 2 4 2 2 2 2 3
Average c — 1.5 1.0 1.5 2.0 1.0 2.0 1.0 1.0 1.3
Grade 1 0 0 0 3 0 0 0 0 4 0
Grade 2 0 0 0 0 1 0 0 0 0 2
Grade 3 0 0 0 0 3 0 0 0 0 2
Total b 0 0 0 3 4 0 0 0 4 4
Average c — — — 1.0 2.8 — — — 1.0 2.5
Grade 1 0 0 0 1 1 0 0 0 0 0
Grade2 0 0 0 0 1 0 0 0 0 0
Total b 0 0 0 1 2 0 0 0 0 0
Average c — — — 1.0 1.5 — — — — —
From Altmann (1999)
a
Average values for four dogs.
b
Total number of dogs with tissues affected
c
Average grade.
The NOAEL was 12.5 mg/kg bw per day (Altmann, 1999). The study was conducted in accordance
with GLP regulations and followed the US EPA FIFRA pesticide assessment guidelines,
subdivision F (1982), section 83-1 and OECD guideline No. 452 (1981).
The results of three studies of toxicity in dogs indicated that brain acetylcholinesterase activity
was significantly inhibited in males at 5 mg/kg bw per day in the 90-day study, but not in males or
females at 2.9 or 14.4 mg/kg bw per day in the 6-month study, or at 1 or 12.5 mg/kg bw per day (the
highest dose tested) in the 1-year study. Hence, the overall NOAEL for inhibition of brain acetylcholinesterase
activity, in these three studies in dogs was 2.9 mg/kg bw per day.
2.3 Long-term studies of toxicity and carcinogenicity
Mice
In a 2-year study of carcinogenicity, groups of 65 male and 65 female HaM/ICR Swiss, CR
CD-1 albino mice were given diets containing profenofos (purity, 90.6%) at a concentration of 0, 1,
30 or 100 ppm (equal to ingested doses of 0, 0.14, 4.5 and 14.2 mg/kg bw per day in males and 0,
0.19, 5.77 and 19.18 mg/kg bw per day in females, respectively) for 85 weeks (males) or 96 weeks
(females). The test diets were prepared weekly and shipped to the sponsor for analysis. However,
the results of analyses were not provided by the sponsor. Mortality was checked daily, while clinical
signs, individual body weights and food consumption were measured once every 4 weeks. The
PROFENOFOS 403–443 JMPR 2007