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

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45<br />

Table 1. Metabolism of atraz<strong>in</strong>e by hepatocytes from different species <strong>in</strong> vitro<br />

Species<br />

Metabolite<br />

Sprague-<br />

Rhesus<br />

F-344 rat Mouse<br />

Dawley rat<br />

monkey<br />

Goat Gu<strong>in</strong>ea-pig Human<br />

Atraz<strong>in</strong>e (%) ND ND ND 2 60 4 19<br />

DIA (%) 14 12 3 25 18 30 18<br />

DEA (%) 5 6 6 10 20 32 50<br />

DACT (%) 50 54 60 50 9% 10 < 5<br />

Ratio of DEA to DIA 1 : 3 1 : 2 2 : 1 1 : 2.5 1 : 1 1 : 1 3 : 1<br />

Conjugated metabolites<br />

(%)<br />

34 29 30 9 < 1 25 11<br />

From Thede (1988)<br />

DACT, diam<strong>in</strong>ochlorotriaz<strong>in</strong>e; DEA, deethyl-atraz<strong>in</strong>e; DIA, deisopropyl-atraz<strong>in</strong>e; ND, not detected.<br />

In a study of acute oral toxicity conducted <strong>in</strong> compliance with GLP and US EPA test guidel<strong>in</strong>es,<br />

groups of five male and five female HSD:(SD) rats received atraz<strong>in</strong>e as a s<strong>in</strong>gle dose at 4000–<br />

5500 (males) or 2000–5500 (females) mg/kg bw suspended <strong>in</strong> 2% carboxymethyl cellulose. Cl<strong>in</strong>ical<br />

symptoms <strong>in</strong>cluded hypoactivity, ataxia, emaciation, lacrimation, nasal discharge, piloerection,<br />

polyuria and salivation. The surviv<strong>in</strong>g rats recovered with<strong>in</strong> 3–6 days. No organ-specific lesions were<br />

discernible on macroscopic exam<strong>in</strong>ation of the animals. Discoloration of the gastro<strong>in</strong>test<strong>in</strong>al tract <strong>in</strong><br />

the rat may be related to local irritation. The male, female and comb<strong>in</strong>ed oral LD 50<br />

and the 95% confidence<br />

limits (CL) were 3520 mg/kg bw (2290–5400), 3000 mg/kg bw (2090–4300) and 3090 mg/<br />

kg bw (2170–4420), respectively (Kuhn, 1991a).<br />

In a study of acute dermal toxicity, groups of five male and five female Tif:RAIf rats received<br />

atraz<strong>in</strong>e as a s<strong>in</strong>gle application at a dose of 2150 or 3170 mg/kg bw suspended <strong>in</strong> 2% carboxymethyl cellulose<br />

on the shaved back sk<strong>in</strong>. No mortality occurred dur<strong>in</strong>g the 14-day observation period. There were<br />

no treatment-related cl<strong>in</strong>ical signs or gross changes <strong>in</strong> the organs. The dermal LD 50<br />

was > 3100 mg/kg<br />

bw <strong>in</strong> males and females (Sachsse & Bathe, 1976).<br />

In a study of acute dermal toxicity conducted <strong>in</strong> compliance with GLP and OECD test guidel<strong>in</strong>es,<br />

one group of five male and five female Tif:RAIf rats received atraz<strong>in</strong>e as a s<strong>in</strong>gle application at<br />

a dose of 2000 mg/kg bw moistened with 0.5% carboxymethyl cellulose on the shaved sk<strong>in</strong> for 24 h.<br />

No mortality occurred. Cl<strong>in</strong>ical symptoms <strong>in</strong>clud<strong>in</strong>g piloerection and hunched body position were<br />

seen on the first 5 days of application. No organ-specific lesions were discernible on macroscopic<br />

exam<strong>in</strong>ation of the animals. The dermal LD 50<br />

was > 2000 mg/kg bw <strong>in</strong> males and females (Hartmann,<br />

1993).<br />

In a study of acute toxicity after exposure by <strong>in</strong>halation that was conducted <strong>in</strong> compliance<br />

with GLP and OECD test guidel<strong>in</strong>es, one group of five male and five female Tif:RAIf rats was<br />

exposed to atraz<strong>in</strong>e at an average air concentration of 5148 mg/m 3 for 4 h. No mortality occurred.<br />

Rats showed piloerection, hunched posture, dyspnea, and reduced locomotor activity. All animals<br />

recovered with<strong>in</strong> 5 days. No organ abnormalities were recorded. The median lethal concentration<br />

(LC 50<br />

) was > 5148 mg/m³ (5.15 mg/l) (Hartmann, 1989).<br />

In a study of acute toxicity after exposure by <strong>in</strong>halation that was conducted <strong>in</strong> compliance with<br />

GLP and US EPA test guidel<strong>in</strong>es, one group of five male and five female Sprague-Dawley rats was<br />

ATRAZINE 37–138 JMPR <strong>2007</strong>

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