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

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283<br />

(e)<br />

Dermal sensitization<br />

The dermal sensitization potential of dimethomorph (purity, 98.0%) was <strong>in</strong>vestigated <strong>in</strong> male<br />

Crl (HA)BR gu<strong>in</strong>ea-pigs via the maximization test of Magnusson & Kligman. In two pre-test studies,<br />

four males received 0.1 ml of dimethomorph <strong>in</strong>tradermally at a concentration of 1%, 5%, 10%,<br />

15%, and 25% <strong>in</strong> m<strong>in</strong>eral oil and another four males received dimethomorph topically at a concentration<br />

of 1%, 5%, 10%, and 25% <strong>in</strong> petrolatum occluded for 24 h by patches. All gu<strong>in</strong>ea-pigs <strong>in</strong> both<br />

groups received all doses and were evaluated for sk<strong>in</strong> irritation 24 h and 48 h after application. In the<br />

group treated by <strong>in</strong>tradermal <strong>in</strong>jection, all doses <strong>in</strong>duced dose-dependent sk<strong>in</strong> irritations that were<br />

moderate-<strong>in</strong>tense at 5%. In the group treated by topical application, no irritation was observed at<br />

any dose. For the ma<strong>in</strong> study, the concentrations of 5% for <strong>in</strong>tradermal <strong>in</strong>jection and 25% for topical<br />

application were selected.<br />

Twenty males were <strong>in</strong>duced <strong>in</strong>tradermally with 5% dimethomorph <strong>in</strong> m<strong>in</strong>eral oil and Freund<br />

complete adjuvant and then on day 9 topically with 25% dimethomorph <strong>in</strong> petrolatum. On day 23,<br />

the gu<strong>in</strong>ea-pigs were challenged by topical application of 25% dimethomorph <strong>in</strong> petrolatum. The<br />

negative-control group consisted of 20 males. The study complied with GLP.<br />

No sk<strong>in</strong> irritation was recorded <strong>in</strong> any of the challenged or control gu<strong>in</strong>ea-pigs and the Meet<strong>in</strong>g<br />

concluded that dimethomorph has no sk<strong>in</strong> sensitization potential (Glaza, 1997)<br />

Table 11. Results of studies of acute toxicity with dimethomorph<br />

Isomer Species Stra<strong>in</strong> Sex Route LD 50<br />

(mg/kg bw) LC 50<br />

(mg/l)<br />

Purity (%)<br />

Reference<br />

E : Z Rat CD Male Oral 4300 — NS Kynoch (1985)<br />

E : Z CD Female Oral 3500 — NS Kynoch (1985)<br />

Z Wistar Males<br />

and<br />

females<br />

Oral > 5000 — NS Heusener &<br />

Jacobs (1987a)<br />

E Wistar Male Oral 4715 — NS Heusener &<br />

Jacobs (1987b)<br />

E Wistar Female Oral 4754 — NS Heusener &<br />

Jacobs (1987b)<br />

E : Z Wistar Males<br />

and<br />

females<br />

E : Z Fischer Males<br />

and<br />

females<br />

E : Z Wistar Males<br />

and<br />

females<br />

E : Z Rabbit NZW Males<br />

and<br />

females<br />

E : Z Rabbit NZW Males<br />

and<br />

females<br />

Dermal > 5000 — 98.7 Heusener &<br />

Eberste<strong>in</strong> (1985)<br />

Dermal > 2000 — 98.5 Gardner (1989)<br />

Inhalation — > 4.24 98.7 Jackson & Hardy<br />

(1986)<br />

Dermal Not irritat<strong>in</strong>g — 98.5 Gardner (1989)<br />

Ocular Not irritat<strong>in</strong>g — 98.5 Gardner (1989)<br />

E : Z Gu<strong>in</strong>ea-pig Crl (HA)BR Male Dermal No sensitization — 98.0 Glaza (1997)<br />

NS, not stated; NZW, New Zealand White.<br />

DIMETHOMORPH 273–315 JMPR <strong>2007</strong>

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