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

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181<br />

(iv) Dermal sensitization<br />

In a study of dermal sensitization us<strong>in</strong>g the Magnusson & Kligman maximization test, lambda-cyhalothr<strong>in</strong><br />

(purity, 96.5%) was tested on 20 Dunk<strong>in</strong> Hartley gu<strong>in</strong>ea-pigs. The control group<br />

consisted of 10 gu<strong>in</strong>ea-pigs. In the <strong>in</strong>duction phase, gu<strong>in</strong>ea-pigs received three <strong>in</strong>tracutaneous <strong>in</strong>jections:<br />

lambda-cyhalothr<strong>in</strong> (5% w/v <strong>in</strong> corn oil), Freund complete adjuvant and corn oil (1 : 1), and<br />

lambda cyhalothr<strong>in</strong> (5% w/v <strong>in</strong> Freund complete adjuvant and corn oil (1 : 1). One week later, this<br />

was followed by a topical application (48 h) of lambda-cyhalothr<strong>in</strong> (1% w/v) <strong>in</strong> corn oil. Two weeks<br />

after the topical application the gu<strong>in</strong>ea-pigs received the challenge dose of lambda-cyhalothr<strong>in</strong> (1%<br />

w/v <strong>in</strong> corn oil, 0.05 ml) for 24 h under occlusion. Sk<strong>in</strong> reactions were exam<strong>in</strong>ed immediately and<br />

1 and 2 days after removal of the occlusive dress<strong>in</strong>g. Statements of adherence to QA and GLP were<br />

<strong>in</strong>cluded.<br />

No response to the challenge dose was observed (Pritchard, 1984).<br />

In deviation from what is required <strong>in</strong> the OECD 406 test<strong>in</strong>g guidel<strong>in</strong>e, no sk<strong>in</strong> irritation was<br />

observed <strong>in</strong> the <strong>in</strong>duction phase. The sk<strong>in</strong> was not treated with sodium lauryl sulfate before the topical<br />

application <strong>in</strong> the <strong>in</strong>duction phase. Therefore the test was not been properly performed and no<br />

conclusion can be drawn as to the sk<strong>in</strong> sensitiz<strong>in</strong>g properties of lambda-cyhalothr<strong>in</strong>.<br />

In the IPCS Environmental Health Criteria 99 (IPCS, 1990) document on cyhalothr<strong>in</strong> it is<br />

reported that cyhalothr<strong>in</strong> <strong>in</strong>duced sk<strong>in</strong> sensitization <strong>in</strong> a Buehler test <strong>in</strong> gu<strong>in</strong>ea-pigs. In gu<strong>in</strong>ea-pigs<br />

previously <strong>in</strong>duced with undiluted technical cyhalothr<strong>in</strong>, a moderate sensitization response was<br />

elicited <strong>in</strong> a Magnusson & Kligman maximization test.<br />

2.2 Short-term studies of toxicity<br />

Rats<br />

In a limited 28-day study <strong>in</strong> Wistar rats, which <strong>in</strong>cluded a recovery period, the toxicity of cyhalothr<strong>in</strong><br />

for the liver was <strong>in</strong>vestigated. Groups of 32 male rats received diets conta<strong>in</strong><strong>in</strong>g cyhalothr<strong>in</strong><br />

(purity, 89.2%) at a concentration of 0 or 250 ppm (equivalent to 12.5 mg/kg bw per day). Rats were<br />

checked daily for cl<strong>in</strong>ical signs. Body weights were measured at the start of treatment and weekly<br />

thereafter. After 28 days, eight rats from each group were killed. The rema<strong>in</strong><strong>in</strong>g rats were ma<strong>in</strong>ta<strong>in</strong>ed<br />

on a control diet and eight rats per group were killed after 7, 14 or 28 days. Livers from all rats were<br />

weighed and exam<strong>in</strong>ed histologically and byelectron microscopy and hepatic am<strong>in</strong>opyr<strong>in</strong>e-N-demethylase<br />

activity was measured. A statement of adherence to quality assurance (QA) was <strong>in</strong>cluded.<br />

The body-weight ga<strong>in</strong> of the rats fed cyhalothr<strong>in</strong> decreased dur<strong>in</strong>g treatment and rema<strong>in</strong>ed<br />

decreased until the day of sacrifice. Although there was a tendency for a slight reduction of the<br />

absolute liver weights of the treated rats, relative liver weights were not affected. At the end of the<br />

28-day treatment period, electron microscopy showed significant proliferation of smooth endoplasmic<br />

reticulum <strong>in</strong> only five rats of the group exposed to cyhalothr<strong>in</strong>. Such proliferation was no longer<br />

apparent <strong>in</strong> rats allowed a 7-day recovery. Hepatic am<strong>in</strong>opyr<strong>in</strong>e-N-demethylase activity was elevated<br />

by 66% after 28 days feed<strong>in</strong>g at 250 ppm, but had reverted to control levels 7 days after cessation of<br />

exposure (L<strong>in</strong>dsay et al., 1982).<br />

In a 90-day study, groups of 20 male and 20 female Wistar derived Alderley Park rats were<br />

fed diets conta<strong>in</strong><strong>in</strong>g technical-grade cyhalothr<strong>in</strong> (purity, 89.2%; total pyrethroid content, 92.2%, of<br />

which 96.8% was cyhalothr<strong>in</strong>) at a concentration of 0, 10, 50, or 250 ppm (equal to 0, 0.56, 2.6, and<br />

14 mg/kg bw per day for males and 0, 0.57, 3.2, and 15 mg/kg bw per day for females). Rats were<br />

checked daily for cl<strong>in</strong>ical signs. Detailed cl<strong>in</strong>ical exam<strong>in</strong>ations and body weights were assessed at<br />

the start of treatment and weekly thereafter. Food consumption was measured weekly. Haematology<br />

was performed on 10 males and 10 females per group at the start of the study and after 1 and 3<br />

LAMBDA-CYHALOTHRIN 173–200 JMPR <strong>2007</strong>

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