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

I. SUMMARY
A risk assessment has been conducted on dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP)
because of possible adverse effects identified in rat and mouse oncogenicity, neurotoxicity, and
genotoxicity studies. DDVP is listed under Proposition 65 as a chemical known to the State of
California to cause cancer.
INTRODUCTION
Chemical Identification- DDVP is an organophosphate insecticide used for the control of pests in
enclosed spaces such as buildings and residents, on pets, on vegetables in greenhouses, on
commodities during post-harvest storage, and on livestock. From 1991 to 1993, approximately 4000-
5000 pounds/year of DDVP were used primarily for structural and livestock pest control.
DDVP exerts its toxicological activity primarily through the inhibition of acetylcholinesterase activity.
Signs and symptoms associated with its toxicity included salivation, diarrhea, tremors, and death.
Regulatory History- DDVP is currently under Special Review by the U.S. Environmental Protection
Agency (USEPA). In 1989, the Scientific Advisory Panel of the USEPA recommended that DDVP
oncogenicity classification be changed from a B2 carcinogen to a C carcinogen. Because of
oncogenic risks, most of the food tolerances have been revoked. A revocation of tolerances for
bagged or packaged nonperishable commodities has been proposed. In 1993, the registrations of
DDVP in California for the use on fresh vegetables were voluntarily cancelled by the registrants.
Environmental Fate- DDVP is not likely to persist in the environment since it is volatile, does not bind
to soil, and is hydrolyzed. The half-life of DDVP was 5.2 days in aqueous buffered solution at pH 7.
The half-lives ranged from 9 to 20 days for DDVP in tap water with pH 7.5 to 8.1. DDVP was also
degraded by soil microorganisms with a half-life of 10.2 hours. After foliar application, DDVP residues
on the leaves may be volatilized, hydrolyzed, and absorbed into the plants.
TOXICOLOGY PROFILE
Pharmacokinetics- DDVP was rapidly absorbed by the oral, intravenous, intraperitoneal, and
inhalation routes and slowly absorbed by the dermal route. After absorption, the radioactivity
distributed to major organs including the liver and kidneys. DDVP was metabolized completely by
ester hydrolysis and demethylation. Initial metabolites were mono- and dimethyl phosphates, and
desmethyl DDVP. Once formed, they may be further metabolized. Final metabolites were either
incorporated in tissues or excreted. Major routes of excretion were in the urine and in the exhaled air,
while to a lesser extent in the feces and in the milk. Excretion routes, tissue distribution, and urinary
metabolites in rats were similar following inhalation or oral exposures.
Acute Toxicity- DDVP was more toxic than its metabolites 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 no-pest strips resulted in the inhibition of plasma cholinesterase (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.
Subchronic Toxicity- Subchronic exposures to DDVP resulted in the inhibition of brain, erythrocyte,
or/and plasma ChE activities in humans, rats, mice, dogs, and cows. Clinical signs observed in
laboratory animals were tremors, diarrhea, decreased body weight gain, increased frequency of
salivation and urine staining in rats, and increased activity and urination in dogs. Other effects
included statistically significant decreases in red blood cell parameters (cell counts, hemoglobin, and
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