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

Oral - Human
One hundred and eight patients with infections were treated with DDVP in a granular-resin formulation
as a broad-spectrum anthelmintic agent (Pena Chavarria et al., 1969). The patients were divided into
2 groups: 24 subjects (14 males and 10 females) at the low dose of 6 mg/kg-day and 84 subjects (37
males and 47 females) at the high dose of 12 mg/kg-day. The only clinical sign reported was brief
mild headaches in a few subjects; no details were provided. Both plasma and erythrocyte ChE
activities were inhibited to varying extent according to the data (presented in graphs). The
significance of the data was difficult to determine as no raw data were presented, and the extent of the
inhibition was presented in 25% intervals.
Human subjects (6/group, average body weight of 81 kg) were fed DDVP (0.9 mg) in either gelatin
salad or a premeal capsule containing cottonseed oil three times a day for 21 days (Boyer et al.,
1977). No clinical signs or erythrocyte ChE inhibition were reported. Plasma ChE activity decreased
continuously with dosing. After 21 days, the plasma ChE activities were about (estimated from graph)
40% and 28% of pre-treatment activities for cottonseed and gelatin formulations, respectively. After
termination of exposure, the plasma ChE activity returned to pre-treatment level and the half-life for
the regeneration was calculated to be 13.7 days. The no-observed-adverse effect level (NOAEL) was
reportedly 0.04 mg/kg-day for the calculation of Acceptable Daily Intake by WHO (1993).
Special studies
Additional studies for the consideration of acute toxicity are described in the III.C. SUBCHRONIC
TOXICITY, III.G. DEVELOPMENTAL TOXICITY, and III.H. NEUROTOXICITY sections. The following
are brief descriptions of the studies.
DDVP (100% purity; 0 to 40 mg/kg) was administered to lactating rats by gavage every 2-4 days for 3
weeks (Tracy et al., 1960). The adjusted dosages based on 3 days per week were 4.5, 9, 13, and 17
mg/kg-day. Cholinergic signs of varying severity were observed 10 to 20 minutes after ingestion and
included irritability, salivation, nasal twitching or scratching, sialorrhea, pronounced exophthalmus
with excessive lacrimation, diarrhea, muscle fasciculation, violent tremors, convulsions, and death.
The NOEL was 9 mg/kg-day.
DDVP (0 to 21.0 mg/kg-day) was given to pregnant Sprague-Dawley rats by gavage once daily from
gestational days 6 to 15 (Tyl et al., 1991a). Tremors were observed in the dams of the 21.0 mg/kgday
group with onset within 10-60 minutes after each daily dosing. Other signs of toxicity included
prone positioning, hindlimb splay, circling, vocalization, hypoactivity, labored respiration, ear shaking,
and coprophagia. The NOEL was 3.0 mg/kg-day for cholinergic signs in the dams.
Acute delayed neurotoxicity of DDVP was studied in atropinized chickens after oral administration of
16.5 mg/kg DDVP on day 1 and again on day 22 (Beavers et al., 1988). At sacrifice on day 43, nerve
fiber degeneration and axonal swelling were noted in one of 10 treated chickens.
Two experiments were conducted in the Tunstall Laboratory with rabbits exposed to DDVP by
inhalation. In the first experiment, female Dutch rabbits were exposed to DDVP by inhalation from day
1 of mating
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