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

II. INTRODUCTION
The human health risk assessment has been conducted for the active ingredient dichlorvos (DDVP)
because of adverse effects in oncogenicity, genotoxicity, and neurological studies. DDVP is listed
under California Proposition 65, the Safe Drinking Water and Toxic Enforcement Act of 1986, as a
chemical known to the State of California to cause cancer.
A. CHEMICAL IDENTIFICATION
Dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP) is an organophosphate pesticide. It is
effective against aphids, spider mites, caterpillars, thrips, and white flies. The major use is for space
treatment of food processing, handling, and storage plants; feedlots; stockyards; corrals; holding
pens; animal buildings; poultry houses; as well as commercial and institutional buildings. The only
"direct" food uses are on beef and dairy cattle skin to control insects, as post-harvest treatment of
processed commodities, and in the greenhouses for tomatoes, radishes, lettuce, and cucumbers.
DDVP is also used in homes for insect control. Tolerances are established for the use of DDVP in raw
agricultural and processed commodities (Appendix A).
The primary biological activity for DDVP is through its inhibition of cholinesterase (ChE) enzymes.
ChEs are a family of enzymes found throughout the body that hydrolyze choline esters. In the
nervous system, acetylcholinesterase (AChE) is involved in the termination of impulses across nerve
synapses including neuromuscular junctions by rapidly hydrolyzing the neural transmitter,
acetylcholine. Inhibition of AChE leads to accumulation of acetylcholine in the synaptic cleft which
results in over-stimulation of the nerves followed by depression or paralysis of the cholinergic nerves
throughout the central and peripheral nervous systems. AChE is highly selective, although not
exclusively, for acetyl esters as substrates (Brimijoin, 1992). Another form of cholinesterase,
butyrylcholinesterase (BuChE), preferentially hydrolyses butyryl and proprionyl esters, depending on
the species; however, it will hydrolyze a wider range of esters, including acetylcholine (Brimijoin,
1992). Unlike AChE, the physiological function of BuChE is not known. Although AChE and BuChE
are found in most tissues, their ratio varies from one tissue to another and from one species to
another. In rats, AChE is the predominant form of ChE in the central nervous system and in the
neuromuscular junctions of peripheral tissues such as the diaphragm, skeletal muscle, heart, and
spleen (Gupta et al., 1991; Mendoza, 1976). AChE and BuChE are present in roughly equal
proportions in the liver and kidneys of rats. Non-synaptic AChE is also present to a lesser extent in
peripheral tissues; however, its function is not known (Brimijoin, 1992). Non-synaptic AChE is
essentially the only ChE present in erythrocytes of higher animals. BuChE is the predominant form of
ChE in the plasma of humans; however, the ratio of AChE to BuChE varies greatly from species to
species and between sexes. For example, the AChE:BuChE ratio in human plasma is approximately
1:1000, but closer to 1:2 in female rats and 3:1 in male rats.
In acutely toxic episodes, muscarinic, and nicotinic receptors are stimulated by acetylcholine with
characteristic signs and symptoms occurring throughout the peripheral and central nervous systems
(Murphy, 1986). Peripheral muscarinic effects can include increased intestinal motility, bronchial
constriction and increased bronchial secretions, bladder contraction, miosis, secretory gland
stimulation and bradycardia. Peripheral nicotinic effects include muscle weakness, twitching, cramps
and general fasciculation. Stimulation of muscarinic and nicotinic receptors in the central nervous
system can cause headache, restlessness, insomnia, anxiety, slurred speech, tremors, ataxia,
convulsions, depression of respiratory and circulatory centers, and coma. Death is usually due to
respiratory failure from a combination of peripheral and central effects.
DDVP appears to be more selective for insects than for mammals (van Asperen an Dekhuijzen,
1958). The inhibition by DDVP of mouse brain ChE was reversible while the inhibition of fly head ChE
was irreversible. DDVP also had higher affinity for fly head ChE than for mouse brain ChE. Sustained
atmospheric DDVP concentration as low as 0.015 ug/liter (L) is effective for fly and mosquito control,
but 0.15 ug/L is required for 100% kill in 30 minutes (WHO, 1967).
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