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144<br />

Benzazimide<br />

(az<strong>in</strong>phos-methyl<br />

metabolite <strong>in</strong><br />

rats)<br />

Rat SD Males and<br />

females<br />

(4)<br />

DMSO 98.1 412 (fasted<br />

males)<br />

269 (fasted<br />

females)<br />

CMC NS 576 (fasted<br />

males)<br />

368 (fasted<br />

f emales) 576<br />

(non-fasted<br />

males)<br />

487 (nonfasted<br />

females)<br />

DMSO NS 330 (fasted<br />

males and<br />

females)<br />

Crawford &<br />

Anderson<br />

(1974); Annex 1,<br />

r eference 64 a<br />

Rat<br />

Males and<br />

females<br />

(NS)<br />

Lamb &<br />

A nderson,<br />

(1974); Annex 1,<br />

reference 64 b<br />

Methyl<br />

b enzazimide<br />

(az<strong>in</strong>phos-methyl<br />

metabolite <strong>in</strong><br />

rats)<br />

Rat SD Males and<br />

females<br />

(4)<br />

Crawford &<br />

Anderson<br />

(1974); Annex 1,<br />

r eference 64<br />

Rat<br />

Males and<br />

females<br />

(NS)<br />

CMC NS 412 (fasted<br />

males)<br />

390 (fasted<br />

f emales) 524<br />

(non-fasted<br />

males)<br />

460 (nonfasted<br />

females)<br />

Lamb &<br />

A nderson<br />

(1974); A nnex 1,<br />

r eference 64 b<br />

CMC, carboxymethyl cellulose; DMSO, dimethyl sulfoxide; NS, not stated; NZW, New Zealand White; SD, Sprague-<br />

Dawley.<br />

a<br />

Modified with reference to orig<strong>in</strong>al data.<br />

b<br />

Orig<strong>in</strong>al data not provided.<br />

Groups of 10 male and 10 female CD rats were given az<strong>in</strong>phos-methyl (purity, 93%; <strong>in</strong> corn<br />

oil) at a dose of 0, 0.22, 0.86, 3.44 mg/kg bw per day by gavage for 13 weeks. All rats were exam<strong>in</strong>ed<br />

at least three times per day for mortality and cl<strong>in</strong>ical signs. Food consumption and body weights were<br />

recorded weekly, and water consumption was recorded daily. Food conversion ratios were calculated<br />

as the amount of <strong>food</strong> consumed per unit body weight ga<strong>in</strong>ed. Ophthalmoscopic exam<strong>in</strong>ations were<br />

performed on all rats before the commencement of treatment and on rats <strong>in</strong> the control and the highest<br />

dose groups after 12 weeks of treatment. Haematology and cl<strong>in</strong>ical chemistry parameters (<strong>in</strong>clud<strong>in</strong>g<br />

chol<strong>in</strong>esterase activity) were determ<strong>in</strong>ed at term<strong>in</strong>ation, after which all animals were given a<br />

macroscopic exam<strong>in</strong>ation, and selected organs were removed and weighed. Histopathological exam<strong>in</strong>ation<br />

was performed on selected tissues harvested from rats <strong>in</strong> the control group and <strong>in</strong> the group at<br />

the highest dose, while kidneys, liver and lungs were exam<strong>in</strong>ed <strong>in</strong> all rats.<br />

There were no treatment-related deaths. Salivation was observed <strong>in</strong> males at and above<br />

0.86 mg/kg bw per day from approximately week 3, with the majority of rats be<strong>in</strong>g affected from<br />

week 8 at 0.86 (up to 8 out of 10) and 3.44 mg/kg bw per day (up to 10 out of 10). Salivation was<br />

observed shortly after dos<strong>in</strong>g <strong>in</strong> the majority of males, but occasionally it was seen before dos<strong>in</strong>g or<br />

up to an hour after dos<strong>in</strong>g <strong>in</strong> some animals. Salivation was observed <strong>in</strong>frequently <strong>in</strong> females with the<br />

exception of 2 out of 20 rats at the <strong>in</strong>termediate dose only dur<strong>in</strong>g week 7, and 4 out of 10 rats at the<br />

highest dose only dur<strong>in</strong>g week 9. There were no treatment-related effects on ophthalmoscopy, bodyweight<br />

ga<strong>in</strong>, or <strong>food</strong> and water consumption. However, there was a clear treatment-related effect on<br />

the <strong>in</strong>hibition of plasma butyryl, plasma acetyl, erythrocyte and bra<strong>in</strong> chol<strong>in</strong>esterase activities <strong>in</strong><br />

males and females (Table 3).<br />

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

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