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

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159<br />

reduced motor activity <strong>in</strong> males and females of the control group noted on day 0 was attributed to<br />

overnight fast<strong>in</strong>g. In males, the motor activity was depressed by about 14% at 12 mg/kg bw relative<br />

to that of the controls, with partial recovery on day 7, and complete recovery of activity was seen<br />

by day 14. In females, motor activity appeared to be slower to recover, show<strong>in</strong>g deficits of about<br />

20%, 10% and 8% at 1, 3 and 6 mg/kg bw, respectively, relative to values for the correspond<strong>in</strong>g<br />

controls on day 14.<br />

Dose-related changes <strong>in</strong> locomotor activity were also noted <strong>in</strong> males on day 0, with about<br />

47% and 77% depressions at 6 and 12 mg/kg bw respectively, relative to values for the correspond<strong>in</strong>g<br />

controls. In females, the reductions <strong>in</strong> locomotor activity were about 26%, 15% and 63% at 1, 3<br />

and 6 mg/kg bw respectively, <strong>in</strong> comparison to those for the parallel controls. Complete recovery of<br />

locomotor activity was seen <strong>in</strong> all males and females, except for males at 12 mg/kg bw that showed<br />

a deficit of 20% compared with the controls by day 7. Complete recovery was seen <strong>in</strong> all animals by<br />

day 14. Treatment-related reductions were also seen <strong>in</strong> <strong>in</strong>terval motor and locomotor activities on day<br />

0 after treatment, but recovery was complete by day 7. Habituation was not affected by treatment.<br />

Data on chol<strong>in</strong>esterase activities are shown <strong>in</strong> Table 15.<br />

No <strong>in</strong>tergroup differences were noted <strong>in</strong> term<strong>in</strong>al body weights, bra<strong>in</strong> weight, gross pathology<br />

and histopathology of treated rats of either sex. The NOAEL was 2 mg/kg bw per day on the<br />

basis of a significant reduction <strong>in</strong> bra<strong>in</strong> chol<strong>in</strong>esterase activity at higher doses (Sheets & Hamilton,<br />

1994).<br />

In a short-term study of neurotoxicity, groups of 18 male and 18 female Fischer 344 rats<br />

were given diets conta<strong>in</strong><strong>in</strong>g az<strong>in</strong>phos-methyl (purity, 92.2%) at a nom<strong>in</strong>al dose of 0, 15, 45, or<br />

120 ppm for males (mean <strong>in</strong>take, 0.91, 2.81, or 7.87 mg/kg bw per day) and 0, 15, 45, or 90 ppm<br />

for females (mean <strong>in</strong>take, 1.05, 3.23, or 6.99 mg/kg bw per day) for 13 weeks. Twelve of the rats<br />

<strong>in</strong> each group were used for behavioural test<strong>in</strong>g with half of these be<strong>in</strong>g used for neuropathology.<br />

The rema<strong>in</strong><strong>in</strong>g six males and six females per group were tested for chol<strong>in</strong>esterase activity. There<br />

were no deaths before term<strong>in</strong>al sacrifice. Treatment-related cl<strong>in</strong>ical signs (perianal sta<strong>in</strong>, red lacrimation,<br />

<strong>in</strong>creased reactivity, uncoord<strong>in</strong>ated gait, tremor) were evident by cage-side observations<br />

Table 15. Chol<strong>in</strong>esterase activity (relative to the correspond<strong>in</strong>g controls) <strong>in</strong> rats given<br />

az<strong>in</strong>phos-methyl by gavage<br />

Dose (mg/kg bw)<br />

Chol<strong>in</strong>esterase activity (% relative to correspond<strong>in</strong>g controls)<br />

Plasma a Erythrocytes a Bra<strong>in</strong> a<br />

Males<br />

2 32* 33* 15<br />

6 57* 67* 74*<br />

12 b 50* 63* 88*<br />

Females<br />

1 11 17 5<br />

3 36* 65* 51*<br />

6 c — — —<br />

From Sheets & Hamilton (1994)<br />

a<br />

Six males and six females.<br />

b<br />

Four animals died after treatment on day 0.<br />

c<br />

All six animals <strong>in</strong> the group died after treatment on day 0.<br />

*<br />

Significantly different from the correspond<strong>in</strong>g controls (p ≤ 0.05)<br />

AZINPHOS-METHYL 139–172 JMPR <strong>2007</strong>

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