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Dichlorvos (DDVP) Risk Characterization Document - California ...

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Dichloroethanol was detected in the urine of a volunteer after inhalation exposure of <strong>DDVP</strong> (purity not<br />

specified, a nominal concentration of 38 ug/L) for 105 minutes (Hutson and Hoadley, 1972).<br />

Other Studies<br />

Metabolism in other species (mice, hamsters, and pigs) proceeded at different rates compared to<br />

those for rats, but the metabolites were similar (Hutson and Hoadley, 1972; Page et al., 1971; Potter<br />

et al., 1973a; Potter et al., 1973b; Loeffler et al., 1976).<br />

In vitro studies using rat subcellular fractions showed that <strong>DDVP</strong> was metabolized by the liver<br />

enzymes in the soluble and mitochondrial fractions (Hodgson and Casida, 1962). Desmethyl <strong>DDVP</strong><br />

was found in both rat liver microsomal and cytosolic fractions indicated that demethylation occurred in<br />

both fractions (Hutson et al., 1971). Using rat liver supernatant fraction, Dicowsky and Morello (1971)<br />

showed that the metabolism of <strong>DDVP</strong> to desmethyl <strong>DDVP</strong> was glutathione dependent. The hydrolysis<br />

of <strong>DDVP</strong> to dimethyl phosphate and dichloroacetaldehyde, as well as the metabolism of desmethyl<br />

<strong>DDVP</strong> to dichloroacetaldehyde and monomethyl phosphate, were glutathione independent.<br />

In a recent study, Holstein cows (3/group) were given <strong>DDVP</strong> (0, 2, 6, or 20 ppm based on dry matter<br />

in the feed) in capsules by gavage twice daily for 28 days (March et al., 1993). The estimated dosage<br />

based on average amount of <strong>DDVP</strong> in the capsules for each group and a body weight of 650 kg were<br />

0.062, 0.17, and 0.63 mg/kg-day. Milk samples, as a composite of evening and morning samples<br />

when possible, were collected periodically from days 1 to 28 of the treatment period. Cows were<br />

sacrificed at the end of the experiment and tissues (muscles, fat, liver, and kidneys) were collected.<br />

All milk and tissue samples showed <strong>DDVP</strong> residue levels at below the limit of quantitation (0.01 ppm).<br />

Cows and goats were treated with <strong>DDVP</strong> ( 32 P, 67-78% purity) by three routes of exposure (Casida et<br />

al., 1962). Cows were exposed to <strong>DDVP</strong> by intravenous (1 mg/kg), subcutaneous (1 mg/kg), and oral<br />

(1 or 20 mg/kg) administrations. Goats were exposed to <strong>DDVP</strong> by subcutaneous (1.52 mg/kg)<br />

injections only. For both species and all routes of exposure, <strong>DDVP</strong> was hydrolyzed into mono- and<br />

dimethyl phosphates, and to a lesser extent desmethyl <strong>DDVP</strong> and inorganic phosphate.<br />

Unmetabolized <strong>DDVP</strong> (recovered in the organosoluble fraction) was found in the milk in the first 2<br />

hours after administration. After 8 hours, the amount of organosoluble products in the milk was below<br />

detection limit as the majority of the radioactivity was due to hydrolysis products. Over 80% of the<br />

dose was excreted in the urine and feces after 96 hours.<br />

Studies conducted on farm animals showed no detected residues in the milk, meat, or meat by<br />

products of cows, goats, and steers sacrificed 1 or more days after single or multiple dermal<br />

applications of <strong>DDVP</strong> (Shell Chemical Co., 1968). Cows were treated with <strong>DDVP</strong> after milking. When<br />

hogs were given <strong>DDVP</strong> (9495 ppm) daily in the diet for 90 days, no residues were found in the tissues<br />

except for the large intestines. Immediately after dosing, the mean residue level in the large intestines<br />

was 0.36 ppm. After 24 hours, the level declined to 0.16 ppm (MDL= 0.02 ppm).<br />

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