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

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199<br />

and motor activity. In each study, five rats of each sex were killed on day 15 and bra<strong>in</strong>, eyes, muscle,<br />

nerves, sp<strong>in</strong>al cord and sp<strong>in</strong>al ganglia were analysed.<br />

One male rat <strong>in</strong> each of the groups at 20 and 40 mg/kg bw of the additional study was found<br />

dead on the day after dos<strong>in</strong>g. Cl<strong>in</strong>ical signs were seen <strong>in</strong> male rats dosed at 20 and 40 mg/kg bw. The<br />

signs (similar <strong>in</strong> both studies) developed between 3 to 8 h after dos<strong>in</strong>g and resolved by 3 days after<br />

dos<strong>in</strong>g. The signs <strong>in</strong>cluded abnormal/splayed gait, thrash<strong>in</strong>g, prostration, vocalization, piloerection,<br />

hunched posture, unkempt appearance, soiled/sta<strong>in</strong>ed body areas and diarrhoea. The signs <strong>in</strong> females<br />

were similar but lower <strong>in</strong> frequency. In addition to these signs there were also isolated cases of<br />

twitch<strong>in</strong>g, tremors, abasia, hypersensitivity, pale eyes, soft faeces and th<strong>in</strong>n<strong>in</strong>g of the fur. Dur<strong>in</strong>g the<br />

FOB conducted 5 h after dos<strong>in</strong>g, gait abnormalities and cl<strong>in</strong>ical signs of <strong>in</strong>creased reactivity were<br />

seen <strong>in</strong> most male rats at 20 and 40 mg/kg bw. In females the signs were less frequent. In the groups<br />

at 20 and 40 mg/kg bw there was an <strong>in</strong>crease <strong>in</strong> very slight to slight sporadic fibre degeneration<br />

<strong>in</strong> the sciatic nerve. The changes were more frequent <strong>in</strong> the proximal than <strong>in</strong> the distal part of the<br />

nerve.<br />

The NOAEL was 4 mg/kg bw on the basis of death, cl<strong>in</strong>ical signs, f<strong>in</strong>d<strong>in</strong>gs <strong>in</strong> the FOB and<br />

degenerative changes to the sciatic nerve at doses of 20 mg/kg bw and higher (JECFA, 1996; Fokkema,<br />

1994b).<br />

Zeta-cypermethr<strong>in</strong><br />

5. <strong>Toxicological</strong> studies<br />

5.1 Acute toxicity<br />

(a)<br />

Oral and dermal toxicity<br />

The acute toxicity of zeta-cypermethr<strong>in</strong> is summarized <strong>in</strong> Table 10.<br />

Cl<strong>in</strong>ical signs <strong>in</strong>duced by zeta-cypermethr<strong>in</strong> were similar to those <strong>in</strong>duced by cypermethr<strong>in</strong>,<br />

i nclud<strong>in</strong>g tremors, staggered gait, writh<strong>in</strong>g, abnormal posture, squ<strong>in</strong>t<strong>in</strong>g eyes, walk<strong>in</strong>g on toes,<br />

splayed h<strong>in</strong>dlimbs and clonic convulsions, ma<strong>in</strong>ly conf<strong>in</strong>ed to the first 24 h after dos<strong>in</strong>g (Freeman,<br />

1999a; Freeman, 1999b)<br />

Table 10. Studies of acute toxicity with zeta-cypermethr<strong>in</strong><br />

Species Sex Stra<strong>in</strong> Route Vehicle Purity (%) LD 50<br />

(mg/kg bw) Reference<br />

Rat M SD Oral 5% <strong>in</strong> corn oil 88.2 134 Freeman (1989)<br />

F<br />

86<br />

Rat M SD Oral 5% <strong>in</strong> corn oil 91.2 257 Freeman (1999a)<br />

F<br />

367<br />

Rat M SD Oral 5% <strong>in</strong> corn oil 86.0 269 Freeman (1999b)<br />

F<br />

285<br />

Rabbit M NZW Dermal Undiluted 88.2 > 2000 Freeman (1990b)<br />

F<br />

F, female; M, male; NZW, New Zealand White.<br />

(b)<br />

Dermal and ocular irritation<br />

After the application of zeta-cypermethr<strong>in</strong> technical (0.5 ml; purity, 88.2%) to the <strong>in</strong>tact sk<strong>in</strong><br />

of New Zealand White rabbits (three of each sex) for 4 h under semi-occlusive dress<strong>in</strong>gs, erythema<br />

CYPERMETHRINS X-X JMPR <strong>2006</strong>

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