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

soluble DDVP derivatives. Other metabolites included inorganic phosphate, two-carbon fragments
(glycine and serine), phosphate ions, and chloride ions.
Rats (strain not specified) were given DDVP ( 14 C and 36 Cl, purity not specified; 0.99 mg/male rat and
0.72 mg/female rat) by gavage (Hutson et al., 1971). Urine, feces, and exhaled air were collected
every day for 4 days. Radioactivity in tissues was also determined. Additional female rats were used
for the determination of metabolites in the urine and the liver. There was no difference in the
excretion patterns between sexes. After 4 days (daily result not given), the percentages of
administered doses in the urine, feces, and exhaled air were 12.8-18.2%, 3.4-4.8%, 36.8-38.8%,
respectively. The identified urinary metabolites included hippuric acid (8.3% of total urinary
radioactivity), desmethyl-DDVP (10.9%), and 2,2-dichloroethyl-B-d-glucopyranosiduronic acid (27%),
while no unmetabolized DDVP, dichloroacetaldehyde or dichloroacetic acid was found. Of the tissues
examined, the highest level of radioactivity (4.4-5.0% of dose) was in the liver. Analysis of the liver
tissue showed that 75% of the radioactivity was associated with glycine, serine, and cystine in the
protein hydrolysate fraction.
Rats (Crl:CD (SD) BR) were given DDVP ( 14 C, purity not specified) either as a single intravenous dose
(1 mg/kg), by gavage as a single dose (0.8 mg/kg or 21 mg/kg), or by gavage as multiple doses (0.8
mg/kg) for 16 days (Cheng, 1989 and 1991). Radioactivity in the tissues and carcasses was
determined 7 days after dosing. Urine, feces, and exhaled air as CO 2 were monitored for 7 days after
dosing. Clinical signs, such as tremors and salivation, were observed 2.5 hours after gavage dosing
in the 21 mg/kg group. There were no differences in the tissue distribution and excretion patterns
between the dosing regiment or sexes. Consistent with the earlier studies, the liver and kidneys
contained higher levels of radioactivity than other organs (lung, spleen, uterus, and bone). For both
routes of administration, the percent of total dose excreted ranged from 40 to 58% in the exhaled air,
10-17% in the urine, and 4-7% in the feces. The majority of the radioactivity in the exhaled air and
excreta was eliminated within 24 hours after dosing. The major metabolites in the urine and feces
were hippuric acid and urea. Glucuronide conjugates and other dehalogenated products were not
positively identified.
Intravenous - Rat
Rats (Carworth Farm strain E) were given DDVP (purity not specified, 0.83 mg/kg) by intravenous
injection (Blair et al., 1975). DDVP was distributed primarily in the kidneys. Levels in the other tissues
(blood, liver, fat, testes, and brain) were 0.01 to 0.1 ug/g, at the limits of detection for the analysis
method used. DDVP degradation in the kidneys was rapid as the levels decreased from 1.44-2.25
ug/g at 10 minutes to 0.15-0.80 ug/g at 30 minutes after dosing.
The kinetics after intravenous administration to rats (Crl:CD (SD) BR) was similar to those for gavage
dosing (Cheng, 1989 and 1991) (see discussion under Oral - Rat section).
Intraperitoneal - Rat
The kinetics of DDVP in the rat (strain not specified) after intraperitoneal administration followed
similar kinetics as those for the oral route (Casida et al., 1962). However in the study conducted by
Hutson et al. (1971), the amount of radioactivity in the urine (35.0% of dose) was higher than that for
exhaled air (18.6%). The major metabolite in the urine was dichloroethanol glucuronide, with hippuric
acid and desmethyl DDVP as minor metabolites.
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