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

B. ACUTE TOXICITY
Summary: The acute toxicities of technical grade DDVP, selected formulations, and metabolites are
presented in Tables 1 and 2. The LD 50 of DDVP was at least 9 times more toxic than its metabolites
(LD 50 of 250 mg/kg for dichloracetic acid) as determined by the magnitude of the 72 hour lethal dose
after intraperitoneal administration. Human exposure of DDVP by ingestion and from the use of nopest
strips resulted in the inhibition of plasma ChE activity, but not erythrocyte ChE activity. Acute
effects observed in laboratory animals from oral or inhalation exposures included diarrhea, irritability,
salivation, lethargy, pupillary constriction, tremors, decreased neuromuscular functions, and death.
TECHNICAL
Gavage - Rat
In a range finding study, rats (Sprague-Dawley Crl:CD.BR, 1/sex/group) were exposed to a single
dose of DDVP (97.87% purity; 0, 0.1, 0.5, 1, 10, 20, 30, 40, 60, 70, or 80 mg/kg) in water by gavage
and observed for 24 hours (Lamb, 1992). No clinical effects were observed at 0.1 and 0.5 mg/kg.
There was a dose-related increase in the number and severity of the cholinergic effects at 1 mg/kg
and higher concentrations. Gait alterations (rocking, lurching, swaying, and prostration) and pupil
constriction were observed in the 1, 10, and 20 mg/kg groups. Tremors and reduced
forelimb/hindlimb grasp were additional effects found in the 30 mg/kg group. At 40 mg/kg and higher
concentrations, rats were also severely affected with labored respiration and salivation. One male rat
of the 80 mg/kg group died.
Based on the results of the range finding study, the full study on neurotoxicity was conducted in rats
(Sprague-Dawley Crl:CD.BR, 12/sex/group) with DDVP (97.87% purity) at 0.5, 35, and 70 mg/kg
given by a single gavage dose (Lamb, 1993a). At 35 and 70 mg/kg, the effects observed in both
groups (except when noted) included altered posture, clonic convulsions, whole body tremors,
constricted pupils (males only), salivation, increased eye prominence, decreased muscle tone, altered
respiration, pale skin, poor grooming, increased mean time to first step, impaired mobility and gait,
decreased arousal, decreased rearing, absence of approach response (except for 35 mg/kg females),
absence of touch response, absence of tail pinch response, lack of response to olfactory stimuli (70
mg/kg only), absence of pupil response, impaired air righting reflex, reduced hindlimb resistance,
reduced grip strength (70 mg/kg), impaired rotarod performance, increased hindlimb foot splay (70
mg/kg only), increased duration of catalepsy, decrease in body temperature, and reduced motor
activity. Recovery of functional observational battery parameters and locomotor activity was evident
by day 7 for all animals. Six rats of the 70 mg/kg group died. Consistent with the observations in the
range finding study, the NOEL was 0.5 mg/kg based on treatment-related cholinergic signs at 35 and
70 mg/kg.
Intraperitoneal - Rat
Adult male Long Evans rats (12-28/group) were exposed to a single dose of DDVP (96% purity) at 0,
5, 10, or 30 mg/kg by intraperitoneal injection for the determination of delayed neuropathy using a
functional observational battery (Ehrich et al., 1993). Atropine was given before treatment, 1 hour
after treatment to those with cholinergic signs, and 2-3 hours after treatment to all animals. At 4 hours
after treatment, four rats from each group were sacrificed in order to determine brain and spinal cord
acetylcholinesterase and neurotoxic esterase activities. Spinal cord ChE as well as brain and spinal
cord neurotoxic esterase activities were significantly (p @ 0.05) reduced by A 30% in a dose-related
manner for all doses. Brain ChE activity was significantly (p @ 0.05) depressed by A 20% only in the
10 and 30 mg/kg groups. There was no treatment-related effect on the body weights. Functional
observational battery showed alterations in the response to approach and activity after 7 to 21 days of
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