TOXICOLOGICAL PROFILE FOR
 

DICHLORVOS
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 1997 
DICHLORVOS ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by 

the Agency for Toxic Substances and Disease Registry. 
DICHLORVOS iii 

UPDATE STATEMENT 

Toxicological profiles are revised and republished as necessary, but no less than once every three 

years. For information regarding the update status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology/Toxicology Information Branch
 

1600 Clifton Road NE, E-29
 

Atlanta, Georgia 30333
 















DICHLORVOS 1 

1. PUBLIC HEALTH STATEMENT
 

This public health statement tells you about dichlorvos and the effects of exposure.
 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites
 

in the nation. These sites make up the National Priorities List (NPL) and are the sites
 

targeted for long-term federal cleanup. Dichlorvos has been found in at least 3 of the
 

1,430 current or former NPL sites. However, it’s unknown how many NPL sites have been
 

evaluated for this substance. As more sites are evaluated, the sites with dichlorvos may
 

increase. This is important because exposure to this substance may harm you and because
 

these sites may be sources of exposure.
 

When a substance is released from a large area, such as an industrial plant, or from a
 

container, such as a drum or bottle, it enters the environment. This release does not always
 

lead to exposure. You are exposed to a substance only when you come in contact with it.
 

You may be exposed by breathing, eating, or drinking the substance or by skin contact.
 

If you are exposed to dichlorvos, many factors determine whether you’ll be harmed. These
 

factors include the dose (how much), the duration (how long), and how you come in contact
 

with it. You must also consider the other chemicals you’re exposed to and your age, sex,
 

diet, family traits, lifestyle, and state of health.
 

1.1 WHAT IS DICHLORVOS? 

Dichlorvos is a synthetic organic chemical used as an insecticide. Dichlorvos does not occur 

naturally in the environment, but is manufactured by industry. Dichlorvos is sold under many 

trade names including Vapona®, Atgard®, Nuvan®, and Task®. Dichlorvos may also be 

called DDVP, which is an abbreviation for its full chemical name. Pure dichlorvos is a dense 

colorless liquid that evaporates easily into the air and dissolves slightly in water. Dichlorvos 

has a sweetish smell and readily reacts with water. The dichlorvos used in pest control is 
DICHLORVOS 2 

1. PUBLIC HEALTH STATEMENT 

diluted with other liquids and used as a spray. It can also be incorporated into plastic that 

slowly releases the chemical. The dichlorvos present at hazardous waste sites will most likely 

be in a liquid solution or as solid plastic pellets or strips. 

Dichlorvos is manufactured by a reaction between two other chemicals called chloral and 

trimethyl phosphite. It is also manufactured by heating a chemical called trichlorfon. In 

1984, about 1 million pounds of dichlorvos was manufactured in the United States. The main 

uses of dichlorvos are for insect control in food storage areas, greenhouses, and barns, and for 

parasite control in livestock. Dichlorvos is generally not used on outdoor crops. It is 

sometimes used for insect control in workplaces and the home. Veterinarians also use it to 

control parasites in pets. Dichlorvos was the active ingredient in “No-Pest Strips,” but is no 

longer used for this purpose. You will find further information on the physical properties and 

uses of dichlorvos in Chapters 3 and 4 of this profile. 

1.2 WHAT HAPPENS TO DICHLORVOS WHEN IT ENTERS THE ENVIRONMENT? 

Dichlorvos enters the air, water, and soil during its manufacture and use. Wastes containing 

dichlorvos that are generated during its manufacture and use are sometimes disposed of in 

landfills. It can enter the environment from these landfills. Dichlorvos also enters the 

environment from accidental spills during transport and leaks from storage containers. 

Dichlorvos evaporates easily into the air, which is why it is usually used in enclosed areas. 

Once in the air, it can react with water vapor and be broken down. The higher the 

temperature and the humidity, the more rapidly dichlorvos is broken down. Experiments in 

greenhouses and food storage areas show that 90% of the applied dichlorvos disappeared in 

3-6 hours. The products of this breakdown are two chemicals called dimethyl phosphate and 

dichloroacetaldehyde. These chemicals are less harmful than dichlorvos and are not believed 

to cause health effects in people. 

If dichlorvos is spilled into a lake or river, it will dissolve in the water. Some dichlorvos will 

then evaporate into the air, but most of it will be broken down when it reacts with the water. 
DICHLORVOS 3 

1. PUBLIC HEALTH STATEMENT 

The less acid the water is, the more rapidly dichlorvos is broken down. Bacteria and other 

microorganisms (microscopic plants and animals) in lakes and rivers can also break down 

dichlorvos. In an experiment where dichlorvos was applied to a pond, 50% of the chemical 

was broken down in 24-36 hours. 

Dichlorvos does not seem to bind to soil. This means it can move through soil fairly rapidly. 

The breakdown in soil is less rapid than in air or water. Dichlorvos breakdown is most rapid 

in moist soils with low acidity. In a laboratory experiment with soil that contained 200 parts 

of dichlorvos per million parts of soil (200 ppm), 37% of the dichlorvos remained in the soil 

after 3 days. Dichlorvos remains for longer periods in dry, acidic soil. Certain bacteria and 

other microorganisms in the soil can also break down dichlorvos. 

Dichlorvos is not stored, accumulated, or concentrated by plants, fish, animals, or people. 

You will find further information about what happens to dichlorvos in the environment in 

Chapter 5 of this profile. 

1.3 HOW MIGHT I BE EXPOSED TO DICHLORVOS? 

The general population is not likely to be exposed to dichlorvos. It has not been found in 

drinking water in the United States and only very rarely in outdoor air. Dichlorvos has 

occasionally been found on raw foods (fruits, vegetables, grains), but washing and processing 

destroys the residue. Maximum limits (ranging from 0.02 to 2 ppm) have been established by 

the U.S. EPA. Dichlorvos has not been found in prepared foods. 

People living near hazardous waste sites containing dichlorvos or near its manufacturing, 

processing, or storage facilities, could potentially be exposed. Because of the chemical 

properties, the most likely way a person would be exposed is by breathing in air contaminated 

with dichlorvos. Another possible route of exposure is skin contact with soil contaminated 

with dichlorvos. 
DICHLORVOS 4 

1. PUBLIC HEALTH STATEMENT 

You are most likely to be exposed to dichlorvos if you are involved in manufacturing or 

using it. Chemical plant workers, transport workers, and pesticide applicators are the major 

occupational groups that might be exposed. People in these groups are mainly exposed by 

breathing air containing dichlorvos, but significant exposure through the skin can occur as 

well. An estimated 24,000 workers in the United States are exposed to dichlorvos because of 

their occupations. Measured air levels in factories and workplaces have ranged from 0.005 to 

0.08 ppm dichlorvos. 

You might also be exposed to dichlorvos in the home after pesticide application. You are 

most likely to be exposed by breathing air containing dichlorvos, but skin contact with 

contaminated surfaces, or eating food that has been left out during dichlorvos application can 

also result in exposure. Measured levels of dichlorvos in room air immediately after pesticide 

applications have ranged from 0.08 to 2.7 ppm. It has been recommended that people should 

not reenter a room or house treated with dichlorvos until after a lo-hour ventilation period. 

You will find further information on the potential for exposure to dichlorvos in Chapter 5. 

1.4 HOW CAN DICHLORVOS ENTER AND LEAVE MY BODY? 

Dichlorvos can enter your body through your lungs if it is in the air you breathe. It can also 

enter your body through your stomach if it is in your drinking water or food. It can also 

enter through your skin. Dichlorvos is taken into your body very rapidly by any of these 

routes (lungs, stomach, or skin). How much dichlorvos enters your body depends on how 

long you are exposed and the amount to which you are exposed. 

Once dichlorvos enters your body, it goes into your bloodstream and is carried to all the 

organs in your body. There are enzymes in your liver and blood that rapidly break it down. 

These breakdown products are less harmful than dichlorvos. Most of these breakdown 

products quickly leave the body in the urine. Some of these products are broken down 

further and leave your body in your breath. Dichlorvos and its breakdown products are not 

stored in your body. 
DICHLORVOS 5 

1. PUBLIC HEALTH STATEMENT 

You will find further information on how dichlorvos enters and leaves your body in 

Chapter 2. 

1.5 HOW CAN DICHLORVOS AFFECT MY HEALTH? 

Dichlorvos is a member of a group of chemicals called organophosphorus compounds. Some 

of these chemicals are extremely harmful to insects and are widely used as insecticides. At 

higher doses than those used to kill insects, these chemicals can also be harmful to people. 

Dichlorvos can chemically react with an important enzyme in your brain and nerves called 

acetylcholinesterase and stop them from working properly. When this happens, signals sent 

between your nerve cells and to your muscles are disrupted. To understand the harmful 

effects of dichlorvos that might occur at levels of exposure that people are likely to 

experience, scientific studies have been done with people and laboratory animals. To protect 

the public from the harmful effects of toxic chemicals and to find ways to treat people who 

have been harmed, scientists use many tests. 

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, 

and released by the body; for some chemicals, animal testing may be necessary. Animal 

testing may also be used to identify health effects such as cancer or birth defects. Without 

laboratory animals, scientists would lose a basic method to get information needed to make 

wise decisions to protect public health. Scientists have the responsibility to treat research 

animals with care and compassion. Laws today protect the welfare of research animals, and 

scientists must comply with strict animal care guidelines. 

We do not know how much dichlorvos is necessary to cause harmful effects in people. This 

is because few people have been exposed to enough dichlorvos to cause symptoms of 

poisoning. From the results of animal testing, we can estimate that if a person breathed in air 

containing more than 1 ppm dichlorvos for more than one hour, harmful effects might result. 

Accidentally drinking as little as 1 ounce or 30 milliliters (mL) of a pesticide containing 5% 

dichlorvos could also cause harmful effects. Spilling an ounce of the same strength 

dichlorvos solution on your skin and failing to wash it off promptly could also be harmful. 
DICHLORVOS 6 

1. PUBLIC HEALTH STATEMENT 

If you have been poisoned by dichlorvos, you will suddenly feel nauseated, anxious, and 

restless. You may also have teary eyes and heavy sweating. If this happens, you should seek 

medical attention immediately. Emergency rooms have drugs that stop the harmful effects of 

dichlorvos. Further symptoms can include loss of bladder control, muscle tremors, and 

labored breathing. Severe poisoning (5 ounces or more of a 5% dichlorvos solution) can 

result in coma, inability to breathe, and death. 

Most people who have survived poisoning by dichlorvos make a complete recovery, although 

this can sometimes take several months. Dichlorvos poisoning does not appear to cause 

permanent damage to the nerves (a condition called “delayed neuropathy”). 

A few studies have been done on people who have been exposed to dichlorvos in the air in 

their workplaces. When dichlorvos is used properly, air levels of 0.01-0.03 ppm are 

achieved. This level kills most insects within one hour. In tests done with volunteers, 

exposure at about 20 times this level (0.23 ppm) for 2 hours a day for 4 days had no harmful 

effects. In a study in rats exposed to air with very high levels of dichlorvos (up to 34 ppm), 

all the animals died within 3 days. The rats showed similar signs of effects on the nervous 

system as in people that have been poisoned with dichlorvos. In general, harmful effects 

have not been seen in animals exposed to air levels of dichlorvos below 0.5 ppm. In a 2-year 

study in rats, breathing air every day with low-to-moderately high levels (0.006-0.6 ppm) of 

dichlorvos had no effect on how long the rats lived or on their general health. 

In at least one case, a person who drank a pesticide containing dichlorvos died. The doctors 

who treated this patient were unable to tell exactly how much dichlorvos she had taken. 

Volunteers who ate 0.03 milligrams dichlorvos per kilogram body weight (0.03 mg/kg) for 

21 days showed no harmful effects. In studies where animals (rats and mice) have been 

force-fed dichlorvos, about half the animals died when given approximately 100 mg/kg. 

Before the animals died, they showed signs of harmful effects to their nervous systems 

similar to those seen in human poisoning cases. 
DICHLORVOS 7 

1. PUBLIC HEALTH STATEMENT 

Two pesticide workers died after spilling concentrated dichlorvos on their skin and failing to 

wash it off promptly. It is not known exactly how much dichlorvos they absorbed through 

their skin. Experiments in animals show that dichlorvos can be just as harmful when it is 

applied to the skin as when it is breathed in or swallowed. Monkeys that had dichlorvos put 

on their skin (50 mg each day) died after 10 doses. 

It is not known if exposure to dichlorvos can affect fertility or development of the fetus in 

people. Experiments done in animals that were fed or breathed in dichlorvos did not show 

any effect on fertility or health of the offspring. 

There is no evidence that exposure to dichlorvos increases the risk of cancer in people. Rats 

that breathed in air containing dichlorvos for 2 years had the same rate of cancer as rats that 

did not breathe in dichlorvos. However, a 2-year study in rats and mice force-fed dichlorvos 

showed an increase in certain forms of cancer. Rats had increased rates of cancer in the 

pancreas and also had more cases of leukemia than rats that had not been treated with 

dichlorvos. Female mice had a higher rate of a form of stomach cancer. 

The U.S. Department of Health and Human Services (DHHS) has determined that dichlorvos 

may reasonably be anticipated to be a carcinogen (a substance that can cause cancer). The 

International Agency for Research on Cancer (IARC) has determined that dichlorvos is 

possibly carcinogenic to humans. The U.S. EPA has determined that dichlorvos is a probable 

human carcinogen. 

The U.S. EPA has calculated that a lifetime of drinking water containing 0.1 micrograms of 

dichlorvos per liter μg/L) would cause one extra case of cancer in every million people 

exposed to this level. Dichlorvos has not been found in drinking water in the United States. 

You will find further information on how dichlorvos may affect your health in Chapter 2. 
DICHLORVOS 8 

1. PUBLIC HEALTH STATEMENT 

1.6 	 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO DICHLORVOS? 

Two blood tests exist that can determine whether you have been exposed to significant levels 

of dichlorvos. These tests can be performed by any hospital or clinical laboratory. These 

tests measure the activity of two enzymes (called serum cholinesterase and erythrocyte [red 

blood cell] acetylcholinesterase) that are affected by dichlorvos. Dichlorvos affects these 

enzymes at lower levels of exposure than necessary to produce harmful effects. This means 

that if these enzymes have been affected, you will not necessarily have effects on your health. 

Many other insecticides also affect these enzymes. To determine whether you have been 

specifically exposed to dichlorvos, a laboratory test must measure the breakdown products in 

your urine. Tests of this type are not routinely done in hospital laboratories and your doctor 

will have to send a sample to a specialized laboratory. 

You will find further information on how you can be tested for exposure to dichlorvos in 

Chapter 2. 

1.7 	 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government develops regulations and recommendations to protect public health. 

Regulations m be enforced by law. Federal agencies that develop regulations for toxic 

substances include the EPA, the Occupational Safety and Health Administration (OSHA), and 

the Food and Drug Administration (FDA). Recommendations provide valuable guidelines to 

protect public health but cannot be enforced by law. Federal organizations that develope 

recommendations for toxic substances include the Agency for Toxic Substances and Disease 

Registry (ATSDR) and the National Institute for Occupational Safety and Health(NIOSH). 

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, 

or food that are usually based on levels that affect animals, then they are adjusted to help 
DICHLORVOS 9 

1. PUBLIC HEALTH STATEMENT 

protect people. Sometimes these not-to-exceed levels differ among federal organizations 

because of different exposure times (an 8-hour workday or a 24-hour day), the use of 

different animal studies, or other factors. 

Recommendations and regulations are also periodically updated as more information becomes 

available. For the most current information, check with the federal agency or organization 

that provides it. Some regulations and recommendations for dichlorvos include the following: 

•	 The U.S. OSHA has set a permissible exposure limit (PEL) of 1 mg/m3

 (0.11 ppm) 

of dichlorvos for workplace air over a l0-hour workday. 

•	 The U.S. EPA requires reporting of any discharge of dichlorvos to the environment 

that exceeds 10 pounds. The EPA has also designated dichlorvos as a hazardous 

substance and specific regulations regarding its disposal are in effect. 

•	 The U.S. EPA has established maximum permissible levels of dichlorvos in various 

food products ranging from 0.02 to 2 parts per million (ppm). Samples from the 

food supply are regularly tested for dichlorvos. 

Further information on federal and state regulations and recommendations concerning 

dichlorvos is found in Chapter 7. 

1.8 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department or 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology 

1600 Clifton Road NE, Mailstop E-29 

Atlanta, GA 30333 
DICHLORVOS 10 

1. PUBLIC HEALTH STATEMENT 

* Information line and technical assistance 

Phone: (404) 639-6000
 

Fax: (404) 639-63 15 or 6324
 

ATSDR can also tell you the location of occupational and environmental health clinics. 

These clinics specialize in recognizing, evaluating, and treating illnesses resulting from 

exposure to hazardous substances. 

* To order toxicological profiles, contact 

National Technical Information Service
 

5285 Port Royal Road
 

Springfield, VA 22 16 1
 

Phone: (800) 553-6847 or (703) 487-4650
 
DICHLORVOS 11 

2. HEALTH EFFECTS
 

2.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective of the toxicology of dichlorvos. It 

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public 

health. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals and others address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of 

exposure-inhalation, oral, and dermal; and then by health effect-death, systemic, immunological, 

neurological, reproductive, developmental, genotoxic, and carcinogenic effects. These data are 

discussed in terms of three exposure periods-acute (14 days or less), intermediate (15-364 days), and 

chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented in tables and illustrated in 

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or 

lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in 

the studies. LOAELS have been classified into “less serious” or “serious” effects. “Serious” effects are 

those that evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute 

respiratory distress or death). “Less serious” effects are those that are not expected to cause significant 

dysfunction or death, or those whose significance to the organism is not entirely clear: ATSDR 

acknowledges that a considerable amount of judgment may be required in establishing whether an end 

point should be classified as a NOAEL, “less serious” LOAEL, or “serious” LOAEL, and that in some 

cases, there will be insufficient data to decide whether the effect is indicative of significant 

dysfunction. However, the Agency has established guidelines and policies that are used to classify 

these end points. ATSDR believes that there is sufficient merit in this approach to warrant an attempt 
DICHLORVOS 12 

2. HEALTH EFFECTS 

at distinguishing between “less serious” and “serious” effects. The distinction between “less serious” 

effects and “serious” effects is considered to be important because it helps the users of the profiles to 

identify levels of exposure at which major health effects start to appear. LOAELs or NOAELs should 

also help in determining whether or not the effects vary with dose and/or duration, and place into 

perspective the possible significance of these effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and 

figures may differ depending on the user’s perspective. Public health officials and others concerned 

with appropriate actions to take at hazardous waste sites may want information on levels of exposure 

associated with more subtle effects in humans or animals (LOAEL) or exposure levels below which no 

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans 

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of dichlorvos 

are indicated in Table 2-2 and Figure 2-2. Because cancer effects could occur at lower exposure levels, 

Figure 2-2 also shows a range for the upper bound of estimated excess risks, ranging from a risk of 

1 in 10,000 to 1 in 10,000,000 ( 10-4 to 10-7), as developed by EPA. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have 

been made for dichlorvos. An MRL is defined as an estimate of daily human exposure to a substance 

that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified 

duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target 

organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of 

exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic 

effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation 

and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in 

development or are acquired following repeated acute insults, such as hypersensitivity reactions, 
DICHLORVOS 13 

2. HEALTH EFFECTS 

asthma, or chronic bronchitis. As these kinds of health effects data become available and methods to 

assess levels of significant human exposure improve, these MRLs will be revised. 

A User’s Guide has been provided at the end of this profile (see Appendix B). This guide should aid 

in the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 

2.2.1 Inhalation Exposure 

All of the studies discussed in this section were conducted in exposure chambers into which air 

containing dichlorvos was introduced. Thus, some exposure may also have occurred by the oral 

and/or dermal route, since dichlorvos vapor came into contact with chamber surfaces and the bodies of 

the subjects. In some studies, food may have been in the chambers during the exposure. 

Air concentrations of dichlorvos in all of the studies discussed below were expressed in units of either 

μg/L or mg/m3. Since inhalation exposure to dichlorvos is more likely to be to the vapor phase than 

to aerosols, air concentrations are also presented as the equivalent parts per million (ppm). All 

concentrations in the inhalation exposure sections of the Levels of Significant Exposure (LSE) table 

(Table 2-l) and figure (Figure 2-l) are expressed as ppm, as are those for the Minimal Risk Levels 

derived for this profile (Section 2.5). The conversion calculation is described in the footnote to 

Table 2-l and in Appendix A. 

Effective insecticidal air concentrations for dichlorvos are in the range of 0.15-0.25 mg/m3 

(0.017-0.028 ppm) (Hayes 1982). Insects are particularly sensitive to dichlorvos because of a lack of 

organophosphate metabolizing enzymes compared to mammals. Their open gas-exchange system (a 

network of tubules penetrating the body) also allows high concentrations of dichlorvos to reach target 

tissues in the nervous system. 

2.2.1.l Death 

No studies were located regarding death in humans after inhalation exposure to dichlorvos. 

Deaths have been reported in animals after acute-duration inhalation exposure to dichlorvos. In an 

early toxicity study (Durham et al. 1957), male and female Sherman rats were exposed to an 
DICHLORVOS 14 

2. HEALTH EFFECTS 

atmosphere derived from air bubbled through dichlorvos before entering the chamber. The air was 

essentially saturated with dichiorvos. Dichlorvos concentrations in the incoming air were measured in 

one trial: 8 separate determinations averaged 306 mg dichlorvos/m3

 (34 ppm) (range = 

230-341 mg/m3

 or 25-38 ppm). The time until death depended on how long the chamber had been 

pre-equilibrated with the atmosphere containing dichlorvos. The time to death was shorter (as little as 

4.5 hours) in chambers pre-equilibrated for the longest times. Rats were exposed until death occurred, 

which took from 6.9 to 61.9 hours on average. Clinical signs reported before death included slow, 

labored respiration, sialorrhea, and paleness in the extremities. 

In an experiment designed to investigate the toxicity of dichlorvos after spraying in an enclosed area, 

Sherman rats and Rhesus monkeys were placed in a chamber whose walls and ceilings had been 

sprayed with a xylene emulsion containing 2.5% dichlorvos by weight and applied to give 1.08 g/m2 

of surface (Durham et al. 1957). The initial dichlorvos concentration in the air of the chamber was 

about 6 mg/m3 (0.66 ppm); it fell to about 1 mg/m3 (0.11 ppm) after 3 days and then to 0.1 mg/m3 

(0.01 ppm) for the rest of the 2-week exposure. No deaths occurred during this experiment. 

Dichlorvos was determined in this study by a total phosphate method. This method also detects the 

breakdown products of dichlorvos, so these concentrations may be overestimated. 

No deaths were reported in male Swiss CF-1 mice exposed for 16 hours to atmospheres containing 

30 or 55 mg dichlorvos/m3 (3.3 or 6.1 ppm) (Dean and Thorpe 1972) or in male Sprague-Dawley rats 

exposed for 3, 7, or 14 days at levels up to 56 mg dichlorvos/m3 (6.3 ppm) (Schmidt et al. 1979). No 

deaths were reported in pregnant CF-1 mice exposed to 4 mg dichlorvos/m3

 (0.44 ppm) for 7 hours a 

day for 10 days (gestation days 6-15) or in pregnant New Zealand rabbits exposed to the same 

concentration for 7 hours a day for 13 days (gestation days 6-18) (Schwetz et al. 1979). 

Deaths were reported in rabbits from inhalation exposure to dichlorvos in an intermediate-duration 

study (Thorpe et al. 1972). In this experiment, groups of 20 pregnant Dutch rabbits were exposed to 

dichlorvos for 23 hours a day at concentrations of 0, 0.25, 1.25, or 6.25 mg/m3 (0, 0.03, 0.14, or 

0.69 ppm, respectively) for the 28 days of gestation. Sixteen of the 20 rabbits died at the 6.25 mg/m3 

concentration. Nine of these deaths may have been related to an unintentional increase to a level of 

8 mg/m3 (0.88 ppm) for one day during the experiment. Before death, the animals were anorexic, 

lethargic, showed tremors and torticollis, and had nasal discharges and diarrhea; these are all signs of 

dichlorvos neurotoxicity. Some animals in a state of advanced toxicosis were killed. An additional 
 

DICHLORVOS 15 

2. HEALTH EFFECTS 

group of 20 pregnant rabbits was exposed to 4 mg/m3 (0.44 ppm) over the 8-day gestational period. 

Six of these rabbits died during the study, and clinical signs were similar to those observed in the 

6.25 mg/m3

 (0.69 ppm) treatment group. Five of these animals died following an increase in 

dichlorvos concentration due to a filter failure. The maximum concentration due to system failure was 

not given. None of the rabbits exposed at levels of 0.25 or 1.25 mg/m3 (0.03 or 0.14 ppm) died over 

the 28 days of exposure. 

No deaths were reported in pregnant Carworth E rats exposed to atmospheres containing 0, 0.25, 1.25, 

or 6.25 mg/m3

 (0, 0.03, 0.14, and 0.69 ppm, respectively) over their 20-day gestation period (Thorpe 

et al. 1972), in male CF-1 mice exposed to 2.1 or 5.8 mg/m3

 (0.23 and 0.64 ppm, respectively) for 

4 weeks (Dean and Thorpe 1972), or in 20-kg Yorkshire-Landrace pigs exposed for a 24-day period to 

concentrations of 0.092-0.114 mg/m3

 (0.01-0.013 ppm) (Loeffler et al. 1976). 

In the only chronic-duration inhalation study available (Blair et al. 1976), groups of 50 Carworth E 

rats of each sex were exposed 23 hours a day to atmospheres containing dichlorvos at levels of 0, 

0.05, 0.5, or 5 mg/m3 (0, 0.006, 0.06, or 0.6 ppm, respectively) for 2 years. Survival was slightly 

increased in the rats exposed to the higher levels of dichlorvos, compared with controls. Clinical signs 

of intoxication were not observed in the 0.05 and 0.5 mg/m3

 groups. Rats in the 5 mg/m3 group had 

necrosis of the tips of their tails, which was not seen in the control or other treated groups. However, 

because more than half of both sexes of the control rats died in this study, conclusions on the lethality 

of dichlorvos after chronic inhalation exposure cannot be drawn. 

All reliable LOAELs for death in each species and duration category are recorded in Table 2-l and 

plotted in Figure 2-l. 

2.2.1.2 Systemic Effects 

No studies regarding systemic effects in humans after inhalation exposure to dichlorvos were located. 

No studies regarding gastrointestinal, renal, musculoskeletal, endocrine, dermal, or ocular effects in 

animals after inhalation exposure to dichlorvos were located. Most of the systemic effects observed 

after inhalation exposure to dichlorvos are the result of the neurotoxicity of this chemical. 






DICHLORVOS 22 

2. HEALTH EFFECTS 

The highest NOAEL values and all LOAEL values from each reliable study for each systemic effect in 

each species and duration category are recorded in Table 2-l and plotted in Figure 2-l. 

Respiratory Effects. Prior to death, slow, labored respiration was seen in Sherman rats exposed 

to dichlorvos in chambers where the incoming air contained 306 mg/m3 (34 ppm) on average (Durham 

et al. 1957). These signs were seen within two hours of exposure in chambers pre-equilibrated with 

dichlorvos. 

Cardiovascular Effects. Paleness of the extremities, suggesting inadequate perfusion, was seen in 

Sherman rats within 2 hours of exposure in chambers until death occurred (4.5-61.9 hours). The 

incoming air contained, on average, 306 mg/m3 (34 ppm), with a range of 230-341 mg/m3 

(25-38 ppm) (Durham et al. 1957). 

Hematological Effects. Hematological parameters (hemoglobin concentration, erythrocyte 

numbers, total and differential leucocyte numbers, prothrombin time, and kaolin-cephalin coagulation 

time) for rats exposed to atmospheres containing up to 5 mg dichlorvos/m3 (0.6 ppm) for 2 years were 

not significantly different from controls (Blair et al. 1976). 

Hepatic Effects. Increased serum levels of serum glutamic oxaloacetic transaminase (SGOT, now 

identified as aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT, now 

identified as alanine aminotransferase [ALT]), possibly indicating hepatic damage, were observed in 

male Carworth E rats exposed to 5 mg dichlorvos/m3

 (0.6 ppm) in a 2-year inhalation study (Blair et 

al. 1976). No changes in SGOT or SGPT were reported in rats of either sex exposed to 0.06 ppm 

dichlorvos. 

Body Weight Effects. The body weight of male Cat-worth E rats exposed to atmospheres 

containing 5 mg dichlorvos/m3

 (0.6 ppm) for 2 years was consistently 20% or more below the body 

weight of control rats from the tenth week of treatment (Blair et al. 1976). Body weights of female 

rats exposed under the same conditions were not significantly different from controls. 

Metabolic Effects. Decreased serum chloride was reported in male Carworth E rats exposed to 

5 mg/m3

 dichlorvos (0.6 ppm) in a 2-year inhalation study (Blair et al. 1976). The magnitude of this 
 

 

DICHLORVOS 23 

2. HEALTH EFFECTS 

decrease was not reported. No changes in serum chloride were reported in rats of either sex exposed 

to 0.06 ppm dichlorvos. 

2.2.1.3 Immunological and Lymphoreticular Effects 

No studies regarding immunological and lymphoreticular effects in humans or animals after inhalation 

exposure to dichlorvos were located. However, total and differential leucocyte numbers were 

unchanged compared to controls in Carworth E rats exposed to atmospheres containing up to 5 mg/m3 

(0.6 ppm) for 2 years (Blair et al. 1976). 

2.2.1.4 Neurological Effects 

Dichlorvos exerts its toxic effects in humans and animals by inhibiting neural acetylcholinesterase. 

This enzyme is present at cholinergic synapses throughout the central and peripheral nervous systems, 

and is responsible for hydrolyzing acetylcholine released from the pre-synaptic terminal. If this 

enzyme is inhibited, acetylcholine accumulates in the synapse, resulting in increased firing of the 

postsynaptic neuron or increased neuroeffector activity. The consequences of increased cholinergic 

activity in the parasympathetic autonomic nervous system (muscarinic receptors) can include increased 

salivation, lacrimation, perspiration, miosis, nausea, vomiting, diarrhea, excessive bronchial secretions, 

bradycardia, frequent micturition, and incontinence. The effects of increased neuroeffector activity on 

skeletal muscles (nicotinic receptors) can include muscle fasciculations, cramps, muscle weakness, and 

depolarization-type paralysis. Effects on cholinergic synapses in the central nervous system 

(predominantly muscarinic) can result in drowsiness, fatigue, mental confusion, headache, 

convulsions, and coma. These classical symptoms of organophosphate neurotoxicity increase in 

severity and rapidity of onset in a dose-dependent manner (Ecobichon 1991). 

Acetylcholinesterase is also present in erythrocytes where it is known as erythrocyte acetylcholin 

esterase. Both forms of acetylcholinesterase are produced by the same gene (Taylor ek al. 1993). In 

in vitro assays, erythrocyte and neural acetylcholinesterase are inhibited to roughly the same extent 

by exposure to dichlorvos and many other organophosphorus compounds with insecticide activity 

(Hayes 1982). Measurement of erythrocyte acetylcholinesterase is used as a surrogate of the 

inhibition of neural acetylcholinesterase. A cholinesterase capable of hydrolyzing acetylcholine is 

also produced by the liver and circulates in the blood. This enzyme, called serum cholinesterase, is also 

inhibited by 
DICHLORVOS 24 

2. HEALTH EFFECTS 

dichlorvos and is often used as a marker for exposure. The endogenous substrate of this enzyme is 

unknown. Usually, this enzyme is inhibited by dichlorvos at lower levels of exposure than required to 

inhibit neural or erythrocyte acetylcholinesterase (Hayes 1982). 

Male volunteers exposed to atmospheres containing 0.25 or 0.7 mg/m3

 (0.03 or 0.08 ppm) showed no 

signs of neurological toxicity (Blair et al. 1975). One volunteer was exposed to 0.25 mg/m3 for 

10 hours and another was exposed to 0.7 mg/m3

 for 20 hours. Blood samples were not assayed for 

erythrocyte acetylcholinesterase, which would have suggested whether neural acetylcholinesterase 

was affected by the exposure to dichlorvos. Another group of seven male volunteers was exposed to 

dichlorvos-containing atmospheres in a simulated aircraft cabin to learn safe levels for aircraft insect 

control (Witter et al. 1961). In this study, the volunteers were exposed to dichlorvos on 4 consecutive 

days for either one or 2 hours. The average dichlorvos concentration was 0.49 mg/m3 (range, 0.26-0.88 

mg/m3) (0.055 ppm, range 0.029-0.097 ppm) in the first experiment and 2.1 mg/m3 (range, 0.9-3.5 

mg/m3

) (0.23 ppm, range 0.10-0.38 ppm) in a second experiment with the same group. General 

physical examinations were performed and blood samples drawn three times before the beginning of 

the experiment to establish baseline rates of serum cholinesterase and erythrocyte acetylcholinesterase activity. Other samples were taken daily before exposure, thus enzyme activity was 

determined 24 hours after exposure. In the first experiment, no changes were observed in serum 

cholinesterase or erythrocyte acetylcholinesterase in any of the men whether they had been exposed 

for one or 2 hours a day to 0.49 mg/m3 over the 4-day exposure period. Serum cholinesterase was 

slightly inhibited (about 20%) in 2 of 3 volunteers exposed for 2 hours a day for 4 consecutive days at 

2.1 mg/m3

. No changes were seen in erythrocyte acetylcholinesterase in any of the men exposed to 

2.1 mg/m3

 for either one or 2 hours a day over the 4-day period. 

In the same study , groups of 2 rhesus monkeys (one of each sex) were exposed to atmospheres 

containing 0.48, 2.3, 2.6, or 12.9 mg/m3

 (0.053, 0.25, 0.29, or 1.43 ppm, respectively) for 2 hours a 

day on 4 consecutive days (Witter et al. 1961). The blood sampling procedures were the same as 

those used on the humans in this study. At the 0.48 and 2.3 mg/m3

 level, the monkeys were exposed 

with the humans. Exposure for 2 hours a day on 4 consecutive days at 0.48 mg/m3 did not affect 

serum cholinesterase or erythrocyte acetylcholinesterase. Similar exposure at 2.3 and 2.6 mg/m3 did 

not affect erythrocyte acetylcholinesterase, but caused about a 30% inhibition of serum cholinesterase. Exposure at 12.9 mg/m3

 (1.43 ppm) had visible effects on both cholinesterases and produced 

miosis, a clinical sign of organophosphate neurotoxicity. The monkeys exposed at this level showed 

substantial 
DICHLORVOS 25 

2. HEALTH EFFECTS 

inhibition of both cholinesterases from the first day of exposure. Activity fell throughout the 4-day 

exposure period; after the last day of exposure, serum cholinesterase was inhibited about 40-50% in 

both monkeys, and erythrocyte acetylcholinesterase fell about 40% in one monkey and 67% in the 

other. Pronounced miosis was also noted in both monkeys at the end of each 2-hour exposure period, 

but was not observed 24 hours later. No other clinical signs were noted. Serum cholinesterase and 

erythrocyte acetylcholinesterase determinations after exposure was terminated suggested that 

40-50 days were required for a return to pre-exposure levels. 

Rhesus monkeys housed in a chamber whose walls and ceiling had been sprayed with a xylene 

emulsion of dichlorvos were observed for two weeks (Durham et al. 1957). The original concentration 

in the chamber was approximately 6 mg/m3

 (0.66 ppm) and decreased to about 1 mg/m3 (0.11 ppm) 

after 3 days and was about 0.1 mg/m3 (0.01 ppm) for the remainder of the 2-week exposure. Blood 

samples were taken before exposure, after 1 week, after 2 weeks, and after exposure ceased, until 

serum cholinesterase and erythrocyte acetylcholinesterase had returned to pre-exposure values. Signs 

of neurological toxicity were not observed. By the end of the first week, both serum cholinesterase 

and erythrocyte acetylcholinesterase had fallen from their pre-exposure levels. Inspection of a graph 

in this report shows that levels of both blood cholinesterases fell about 50-60% during the first week of 

the study. Serum cholinesterase recovered partially in the third week, but erythrocyte acetylcholinesterase did not. After exposure was ended, the activities of both enzymes returned to pretreatment 

values in about five weeks. 

Ten Sherman rats of each sex housed in the same chamber as the monkeys were also monitored in this 

experiment (Durham et al. 1957). No clinical signs of neurological toxicity were observed in the rats 

over the 2-week exposure period. There was a slight decrease in serum cholinesterase and erythrocyte 

acetylcholinesterase at the end of the first week (about 10% for each enzyme). At the end of 2 weeks, 

no difference was observed between exposed rats and controls. Bronchial and erythrocyte acetylcholinesterase were measured in male Sprague-Dawley rats exposed to atmospheres ranging from 0 to 

56.64 mg/m3

 (0-6.26 ppm) over a 3-day period (Schmidt et al. 1979). A dose-dependent reduction in 

both bronchial and erythrocyte acetylcholinesterase was observed. Bronchial tissue acetylcholinesterase measured in homogenates from treated rats at 0.83 and 1.82 mg/m3

 (0.09 and 0.20 ppm, 

respectively) was lower than in control rats; bronchial tissue acetylcholinesterase was inhibited by 

50% at 1.82 mg/m3

, a dose that did not affect erythrocyte acetylcholinesterase. Erythrocyte 

acetylcholin-esterase was inhibited by 62% at 4.32 mg/m3

 (0.48 ppm) and was more than 80% 

inhibited at 
DICHLORVOS 26 

2. HEALTH EFFECTS 

8.2 mg/m3 (0.91 ppm) after 3 days exposure. The authors reported that “similar” results were found in 

animals exposed for 7- and l4-day periods, but the data were not presented. Because clinical signs or 

pulmonary function parameters were not reported in this study, the toxicological significance of this 

level of bronchial enzyme inhibition in the male Sprague-Dawley rats cannot be assessed. 

Several studies in animals have addressed neurological effects after intermediate-duration inhalation 

exposure to dichlorvos. In a study of pregnant Carworth E rats exposed over their gestation period 

(20 days), some dams exposed to atmospheres containing 6.25 mg/m3 (0.69 ppm) were less active than 

controls (Thorpe et al. 1972). Exposure at 0.25 mg/m3 (0.03 ppm) did not affect erythrocyte or brain 

acetylcholinesterase. Exposure at 1.25 mg/m3 (0.14 ppm) resulted in a 29% inhibition of erythrocyte 

and a 28% inhibition of brain acetylcholinesterase, while exposure at 6.25 mg/m3 resulted in 88% 

inhibition of erythrocyte acetylcholinesterase and an 83% inhibition of brain acetylcholinesterase. 

In the same exposure atmosphere, pregnant Dutch rabbits showed inhibition of 14 and 10% in 

erythrocyte and brain acetylcholinesterase, respectively, at an exposure of 0.25 mg/m3 (0.03 ppm) 

over a period of 28 days (Thorpe et al. 1972). At exposures of 1.25 mg/m3 (0.14 ppm) erythrocyte 

acetylcholinesterase was inhibited 68% and brain acetylcholinesterase was inhibited 56% compared 

to controls. Exposure of Yorkshire pigs for 24 days to atmospheres containing 0.09-0.11 mg/m3 

(0.010-0.012 ppm) had no effect on serum cholinesterase or erythrocyte acetylcholinesterase 

(Loeffler et al. 1976). 

In a 2-year chronic inhalation study with dichlorvos (Blair et al. 1976), 50 Carworth E rats of each sex 

were exposed to atmospheres containing 0, 0.05, 0.5, or 5 mg/m3 (0, 0.006, 0.06, or 0.6 ppm). No 

clinical signs of neurological toxicity were seen in any of the groups. Acetylcholinesterase activity 

was measured in brain and erythrocytes, as was serum cholinesterase, at the end of this study. In male 

animals exposed to 0.05 mg/m3

 (0.006 ppm), no significant differences with control animals were seen 

for any of the cholinesterases. Female animals at this exposure level had a statistically significant 

decrease of 12% in erythrocyte acetylcholinesterase. At 0.5 mg/m3 (0.06 ppm), brain cholinesterase 

was 10% lower compared to controls in both male and female rats. Females at this exposure level 

also showed erythrocyte acetylcholinesterase inhibition of 31%, while the males were unaffected. At 

5 mg/m3 (0.6 ppm), brain acetylcholinesterase was inhibited by 79% and 81% in male and female 

rats, respectively. Erythrocyte acetylcholinesterase inhibition at this dose was 96% in the male rats 

and 95% in the female rats. 
DICHLORVOS 27 

2. HEALTH EFFECTS 

No studies were located in humans or animals describing organophosphate-induced delayed 

neuropathy (OPIDN) after inhalation exposure to dichlorvos. This is a syndrome observed in humans 

and some animal models after recovery from the acute cholinergic effects of certain organophosphorus 

compounds, for example tri-o-cresyl phosphate (Coppock 1995; Johnson 1981). The characteristic 

signs are disturbances of gait, and a “dying-back” type degeneration of motor fibers. Studies on the 

relationship between dichlorvos and OPIDN for parenteral routes of exposure are discussed in 

Section 2.5. 

All reliable NOAELs and LOAELs for neurological effects in each species and duration category are 

recorded in Table 2- 1 and plotted in Figure 2-l. 

2.2.1.5 Reproductive Effects 

No studies were located regarding reproductive toxicity in humans after inhalation exposure to 

dichlorvos. 

In a reproductive toxicity study involving male CF-1 mice, groups of 16 mice were exposed to 

atmospheres containing dichlorvos at 0, 30, or 55 mg/m3 for 16 hours (0, 3.3, or 6.1 ppm) (Dean and 

Thorpe 1972). Following dosing, each male mouse was caged with 3 randomly selected females for 

7 days; this procedure was repeated weekly for a total of 8 weeks. Thirteen days after the presumed 

mating (which occurred by the middle of the week), the female mice were sacrificed and the uteri 

removed for examination. There were no differences between control and treated mice in the number 

of early fetal deaths, late fetal deaths, or live fetuses found in the pregnant females. The percentages 

of pregnancies for females mated to males exposed to 30 or 55 mg/m3

 (3.3 or 6.1 ppm) for 16 hours 

ranged from 67 to 88% and 63-92%, respectively; for controls, the percentages ranged from 73 to 

88%. Under these exposure conditions, dichlorvos did not appear to affect the fertility of male CF-1 

mice. 

In another experiment in this study, similar results were obtained for male mice exposed for 4 weeks 

to atmospheres containing 2.1 or 5.8 mg/m3 (0.23 or 0.64, respectively) dichlorvos for 23 hours a day 

(Dean and Thorpe 1972). 
 

DICHLORVOS 28 

2. HEALTH EFFECTS 

Maternal toxicity was reported in Dutch rabbits exposed throughout gestation to atmospheres 

containing dichlorvos at 4 or 6.25 mg/m3 (0.44 or 0.69 ppm). Sixteen of 20 dams died at the higher 

dose; when the concentration was reduced to 4 mg/m3, 6 of 20 dams died (Thorpe et al. 1972). 

Exposure spikes occurred at both exposure concentrations and may have contributed to the observed 

toxicity. Maternal toxicity was not observed in Carworth E strain rats exposed to atmospheres 

containing 0, 0.25, 1.25, and 6.25 ug/L dichlorvos (0, 0.03, 0.14, and 0.69 ppm) through day 20 of 

pregnancy (Thorpe et al. 1972). 

The NOAELs for reproductive effects are recorded in Table 2- 1 and plotted in Figure 2- 1. 

2.2.1.6 Developmental Effects 

No studies were located regarding developmental toxicity in humans after inhalation exposure to 

dichlorvos. 

Several animal studies examining developmental toxicity during continuous inhalation exposure to 

dichlorvos are available. A study in which pregnant mice and rabbits were exposed to dichlorvos only 

during the organogenesis period of gestation showed no significant effect on development (Schwetz et 

al. 1979). In this study, pregnant CF-1 mice were exposed to 4 mg/m3 (0.44 ppm) dichlorvos for 

7 hours a day during gestation days 6-15. At sacrifice on day 18, no significant effects were seen on 

the mean number of fetuses per litter, the incidence or distribution of resorptions, or on fetal body 

measurements. Twenty control litters and 15 litters from treated animals were examined in this study. 

There was no difference between the litters from controls and dichlorvos-treated dams. Pregnant New 

Zealand rabbits exposed to 4 mg/m3

 (0.44 ppm) for 7 hours a day during gestation days 6-18 also 

showed no evidence of developmental toxicity (Schwetz et al. 1979). Mean number of fetuses per 

litter, incidence or distribution of resorptions and fetal body measurements were similar in 14 control 

litters and 19 treated litters. 

Groups of 15 pregnant Cat-worth E rats were exposed to atmospheres containing 0, 0.25, 1.25, or 

6.25 mg/m3

 (0, 0.03, 0.14, or 0.69 ppm) throughout their 20-day gestation period (Thorpe et al. 1972). 

At the end of 20 days, the rats were sacrificed and the uteri removed for examination. The number of 

live fetuses, late fetal deaths, and resorption sites were noted, and live fetuses were weighed and 

examined for external malformations. Approximately half the fetuses in each litter were processed for 
 

 

DICHLORVOS 29 

2. HEALTH EFFECTS 

alizarin-stained preparations of the skeleton, and the other half were fixed in Bouin’s fluid and 

examined for structural abnormalities of the viscera by transverse sections. Exposure of dams to all 

three concentrations of dichlorvos did not affect the number of fetal resorptions, late fetal deaths, litter 

size, or mean weight per fetus. One fetus in the litter of dams in the 0.25 mg/m3

 group had skeletal 

defects and gastroschisis. Because no other fetuses from dams exposed to the same or higher 

concentrations had these defects, the authors concluded that they were not exposure-related. Brain and 

erythrocyte acetylcholinesterase activities were inhibited 83 and 88%, respectively, in dams in the 

high-exposure (6.25 mg/m3

) group, suggesting that acetylcholinesterase inhibition is not associated 

with teratogenicity. Measurement of acetylcholinesterase activities in the pups was not performed. 

In a parallel experiment conducted on groups of 20 pregnant Dutch rabbits (Thorpe et al. 1972), 

similar results were seen. Dams exposed to dichlorvos at 6.25 mg/m3

 (0.69 ppm), as in the previously 

described rat study, had high mortality (16 of 20 died). Consequently, the doses used in this 

experiment were 0, 0.25, 1.25, 2, and 4 mg/m3 (0, 0.03, 0.14, 0.22, and 0.44 ppm) over the 28-day 

rabbit gestational period. Six of the 20 rabbits exposed to 4 mg/m3 died. In both the 4 and 

6.25 mg/m3 exposure groups, spiking of the exposure concentration occurred. Sizes of litters, fetal 

resorptions, and late fetal deaths were unaffected by inhalation exposure to dichlorvos. Mean fetal 

weights were significantly depressed (23.1 ± 0.98 g for controls and 20.2 ± 0.98 g for the 4 mg/m3 

exposure group), but the authors ascribed this to maternal toxicity. Clinical signs were similar to signs 

for dams exposed to 6.25 mg/m3

; 6 dams out of 20 in this group died during the study. Three fetuses 

from groups that had not been exposed to dichlorvos had gastroschisis. Two dead fetuses from one 

litter in the 4 group had cleft palates, but this may also be a result of maternal toxicity rather 

than a developmental effect. 

The NOAELS for developmental toxicity are recorded in Table 2-l and plotted, in Figure 2-l. 

2.2.1.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.5. 

2.2.1.8 Cancer
 

No studies were located regarding cancer in humans after inhalation exposure to dichlorvos.
 
DICHLORVOS 30 

2. HEALTH EFFECTS 

In a 2-year carcinogenicity study of dichlorvos by inhalation exposure (Blair et al. 1976). groups of 

50 Carworth E rats of each sex were exposed to atmospheres containing dichlorvos at 0, 0.05, 0.5, or 

5 mg/m3

 (0, 0.006, 0.06, or 0.6 ppm) for 23 hours a day. Necropsies were carried out on animals that 

died or were sacrificed because of ill health during the study. At the end of the study, the surviving 

rats were sacrificed, and blood samples taken, necropsies performed, and major organs weighed. 

Major viscera, macroscopic tumors, and blocks of tongue, nasal cavity, trachea, skeletal muscle, eye, 

and lachrymal gland were fixed in formalin and processed for paraffin section. Respiratory tissue 

from a small number (not stated) of control and high-dose animals was examined by electron 

microscope. Only 11 of the unexposed male controls and 25 of the unexposed female controls 

survived to the end of the study. Survival was highest in the rats exposed to the highest concentration 

of dichlorvos (32 of 50 males and 34 of 50 females). Microscopical examination revealed a wide 

range of lesions in all groups; the authors stated that these are commonly seen in old rats of this strain. 

There was a high incidence in control and treated groups of chronic nephrosis, focal myocardial 

fibrosis, degenerative artery disease, lymphoid hyperplasia of the spleen, and testicular atrophy. 

Common tumors in all groups were adenomas of the anterior pituitary gland, parafollicular cell 

adenomas and carcinomas of the thyroid gland, adrenal pheochromocytomas, and mammary 

fibroadenomas in the females. Examination of the lungs (presumably the tissue receiving the highest 

dose) revealed minor changes in all groups. Peribronchial and perivascular lymphoid aggregates, mild 

degrees of bronchiolitis, and focal alveolar thickening were noted. Electron microscopic examination 

of bronchi, bronchioli, and alveoli of a small number of control and high-dose group animals showed 

no differences between the groups. None of the lesions in the study was associated with dichlorvos 

exposure. 

The high mortality of the control animals in this study makes interpretation of the carcinogenicity data 

problematic. The possibility also exists that exposure by the oral and dermal routes occurred since the 

animals received whole-body exposure to dichlorvos vapor in cages rather than nose-only exposure. 

However, no significant increase in neoplastic or non-neoplastic lesions was found in the nasal and 

respiratory tract tissues that presumably received the highest dose of dichlorvos. 
 

DICHLORVOS 31 

2. HEALTH EFFECTS 

2.2.2 Oral Exposure 

2.2.2.1 Death 

Two deaths in humans have been associated with oral exposure to dichlorvos (Hayes 1982). In one 

case, a young woman who drank an undetermined amount of dichlorvos died despite prompt medical 

treatment. In another case, a 19-month-old girl who ate part of a cake-like bait that contained 

dichlorvos died after 4 days (Hayes 1982). The actual bait she consumed was not recovered for 

analysis, but because similar baits were found to contain both dichlorvos and malathion, it is possible 

that an interaction with malathion may have occurred. Malathion had much lower acute toxicity than 

dichlorvos when measured in an LD 50 (lethal dose, 50% kill) study in male Sherman rats; the LD50 

for malathion was 1,375 mg/kg, while that for dichlorvos was 80 mg/kg (Durham et al. 1957). Severe 

cerebral edema was considered the cause of death. 

A number of oral exposure LD50 studies have been done with dichlorvos in rats and mice. Based on 

reported LD50 values, dichlorvos is considered to be of moderate to high acute toxicity (WHO 1989). 

In the most extensive study of this type, dichlorvos was one of 5 chemicals used in a study designed 

to investigate how well an experimentally derived LD50 value would predict the level that would 

result in 1% lethality (LDl value) for CD-l mice (Haley et al. 1975). The LD50 for male mice in this 

study was calculated to be 139 mg/kg, and the LD50 for females was 133 mg/kg. In a subsequent 

study at lower doses, the LDl for the male mice was 84 mgkg (predicted LD1 was 81 mg/kg). In the 

female mice, the LD1 was 95 mg/kg (predicted LD1 was 106 mg/kg). The authors further estimated 

an LD0.1 of 70 mg/kg for male mice and 82 mg/kg for female mice. An LD50 of 110 mg/kg was 

reported in male ICR mice (Takahashi et al. 1987). Dichlorvos administered by gavage in water at a 

dose of 150 mg/kg to male Swiss mice caused 100% lethality within 9 minutes (Mohammad et al. 

1989). 

In Sherman rats, oral LD50 values of 80 mg/kg in males and 56 mg/kg in females were reported 

(Durham et al. 1957). The LD50 for female Wistar rats was reported to be 58.8 mg/kg (Gajewski and 

Katkiewicz 1981) and in male Fischer 344 rats 97.5 mg/kg (Ikeda et al. 1990). Crossbred pigs 

weighing 12-27 kg treated with dichlorvos in gelatin capsules were reported to have an LD50 of 

157 mg/kg (Stanton et al. 1979). 
DICHLORVOS 32 

2. HEALTH EFFECTS 

Other studies have reported deaths in animals after acute-duration oral exposure to dichlorvos. Three 

of 12 greyhound dogs receiving 22 mg/kg in a gelatin capsule died (Snow and Watson 1973). Two of 

the dogs died within 20 minutes of dosing; cyanosis was severe and progressive, and sounds of gas 

passage in the respiratory tract ceased in spite of continued respiratory effort. This was followed soon 

afterwards by respiratory arrest and then cardiac arrest. Another dog dosed at 22 mg/kg was comatose 

for a long period, had repeated convulsive episodes, and died 15.5 minutes after dosing. In castrated 

male (surgery at 10 days of age) and female crossbred pigs treated with dichlorvos in gelatin capsules, 

deaths occurred 15-30 minutes after dosing (Stanton et al. 1979) in a single pig dosed with 

560 mg/kg, in 7 of 8 at 320 mg/kg, in 5 of 8 at 150 mg/kg, and in 2 of 8 at 100 mg/kg. Clinical 

signs observed in these animals included hypoactivity, vomiting, ataxia, muscle fasciculations, 

uncoordinated movements, frothy salivation, and defecation. One white Leghorn hen treated on 

2 consecutive days with 7.1 mg/kg in gelatin capsules also died after the second treatment (Francis et 

al. 1985). Clinical signs were staggering gait, salivation and convulsions. Birds are generally more 

susceptible to organophosphorus compounds due to lack of detoxification pathways. 

Intermediate-duration exposure to dichlorvos has also caused death in experimental animals. In a 

dose-finding study where Osborne-Mendel rats (5 of each sex) were exposed to dichlorvos-containing 

feed at dosages of 0-360 mg/kg/day for a 6-week period, all rats consuming 2180 mg/kg/day died 

(NCI 1977). Exposure to 90 mg/kg/day did not cause any deaths. In a dose-finding study for a 2-year 

carcinogenicity experiment, Fischer 344 rats (10 of each sex) were treated by corn oil gavage 5 days a 

week for 13 weeks over a dosage range of 0-64 mg/kg/day (NTP 1989). All rats receiving 32 and 

64 mg/kg died before the end of the study. Some animals that died were trembling and inactive 

immediately before death. Of the male rats receiving 64 mg/kg, 90% died by the first week of the 

study, while 90% of the male rats receiving 32 mg/kg died in the seventh week of the study. One of 

the 10 male rats receiving 16 mg/kg died, but the authors stated that this was gavage-related. Male 

rats at dosages of 2, 4, and 8 mg/kg survived for 13 weeks. All female rats receiving 32 or 64 mg/kg 

died in the first week. Four of 10 females receiving 16 mg/kg died by the seventh week. All female 

rats receiving 2, 4, and 8 mg/kg survived for 13 weeks. 

In similar intermediate-duration studies in mice, groups of 5 B6C3Fl mice were exposed by feed to 

dosages ranging from 0 to 1,080 mg/kg/day for 6 weeks (NCI 1977). Four of 5 females died at the 

720 mg/kg/day dose; all mice consuming 1,080 mg/kg/day died. No deaths were reported in mice 

consuming 360 mg/kg/day or less. In another study (NTP 1989), groups of 10 B6C3Fl mice of each 
 

DICHLORVOS 33 

2. HEALTH EFFECTS 

sex were dosed by corn oil gavage at levels ranging from 0 to 160 mg/kg for 5 days a week for 

13 weeks. All 10 male mice and 9 of 10 female mice who received 160 mg/kg died. Eight of the 

male mice died in the first week, as did 3 female mice. Five of 10 male mice died after receiving 

80 mg/kg. 

In a chronic-duration study (2 years) where Osborne-Mendel rats of both sexes were exposed through 

feed to doses of 0, 13.5, and 29.3 mg/kg/day, survival was higher in the treated groups than in the 

matched control animals (NCI 1977); 76% of the high-dose and 64% of the low-dose males survived, 

as did 84% of the high-dose and 80% of the low-dose females. The authors stated the rats were in 

poor condition in both In a similar study using Fischer 344 rats (NTP 1989), no significant differences 

were observed in survival among groups of either sex treated by corn oil gavage at doses of 0, 4, or 

8 mg/kg for 5 days a week for 103 weeks. In a 2-year study of B6C3F1 mice, no significant 

differences in survival were noted between groups of either sex exposed through feed to doses of 0, 

57.2, or 114.3 mg/kg/day (NCI 1977). In another 2-year study in B6C3F1 mice (NTP 1989), no 

significant differences in survival were noted among groups treated by corn oil gavage at doses of 0, 

10, or 20 mg/kg for 5 days a week in male mice or at 0, 20, or 40 mg/kg for 5 days a week in female 

mice. 

No deaths were reported in Beagle dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day 

dichlorvos by capsule in corn oil for 52 weeks (AMVAC Chemical Corp. 1990). 

All reliable LD50 values and LOAELs for death in each species and duration category are recorded in 

Table 2-2 and plotted in Figure 2-2. 

2.2.2.2 Systemic Effects 

No studies regarding systemic effects in humans after oral exposure to dichlorvos were located. No 

studies regarding musculoskeletal or metabolic effects in animals after oral exposure to dichlorvos 

were located. Most of the systemic effects of dichlorvos after oral exposure are secondary to the 

neurotoxicity of this chemical. 

The highest NOAEL values and all LOAEL values from each reliable study for each systemic effect in 

each species and duration category are recorded in Table 2-2 and plotted in Figure 2-2. 












DICHLORVOS 46 

2. HEALTH EFFECTS 

Respiratory Effects. No gross or histological evidence of treatment-related damage to the lungs, 

mainstream bronchi, or trachea was observed in B6C3F, mice treated by oral gavage with dichlorvos 

at 20 mg/kg/day (males) or 40 mg/kg/day (females) for 5 days a week for 2 years (NTP 1989) or in 

Beagle dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day by capsule for 52 weeks (AMVAC 

Chemical Corp. 1990). 

Cardiovascular Effects. No gross or histological evidence of treatment-related damage to the 

heart was seen in Fischer 344 rats treated with up to 8 mg/kg/day dichlorvos for 5 days a week for 

2 years. Similar results were seen in B6C3Fl mice treated in the same study with dichlorvos at 

20 mg/kg/day (males) or 40 mg/kg/day (females) for 5 days a week (NTP 1989) or in Beagle dogs 

(groups of 4 of each sex) receiving up to 3 mg/kg/day by capsule for 52 weeks (AMVAC Chemical 

Corp. 1990). 

Gastrointestinal Effects. Diarrhea, sometimes bloody, and vomiting were observed in greyhound 

dogs exposed orally to dichlorvos in gelatin capsules at a single dose of 11 mg/kg (Snow and Watson 

1973). Vomiting and defecation were also reported in crossbred pigs dosed at 18 mg/kg in gelatin 

capsules (Stanton et al. 1979). Excessive salivation and defecation were observed before death in male 

Swiss mice receiving 150 mg dichlorvos emulsion/kg by water gavage (Mohammad et al. 1989). 

Diarrhea was reported in Osborne-Mendel rats receiving 90 mg dichlorvos kg/day over a 3-week 

period (NCI 1977). This diarrhea was so severe that the dichlorvos dose was reduced to 29 mg/kg/day 

for the remainder of this 2-year study. Similar signs were seen in B6C3F, mice receiving 

360 mg/kg/day dichlorvos in the same study (NCI 1977), and dosages were reduced to 114 mg/kg/day 

in these mice. Mild diarrhea was reported throughout a 2-year study in male rats receiving 4 or 

8 mg/kg/day dichlorvos (NTP 1989). Diarrhea and vomiting may reflect a local irritant action of 

dichlorvos on the gastrointestinal tract; however, these signs may also be caused by muscarinic 

cholinergic stimulation (Ecobichon 1991). 

No gross or histological evidence of treatment-related damage to gastrointestinal tissues (cecum, colon, 

duodenum, esophagus, ileum, jejunum, rectum and stomach) was found in Fischer 344 rats treated 

with up to 8 mg/kg/day dichlorvos by gavage 5 days a week for 2 years (NTP 1989) or in Beagle 

dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day by capsule for 52 weeks (AMVAC 

Chemical Corp. 1990). Significantly increased neoplastic lesions were found in the forestomach of 

female mice treated in the NTP study at doses of 20 and 40 mg/kg/day (see Section 2.2.2.8). 
DICHLORVOS 47 

2. HEALTH EFFECTS 

Hematological Effects. A 10% increase in hematocrit was seen in greyhound dogs exposed to a 

single dose of 11 mg/kg and showing moderate to severe signs of toxicity (Snow and Watson 1973). 

Total plasma proteins increased in all but one dog that received 22 mg/kg. Diarrhea was also 

observed, thus the increase in hematocrit and total plasma proteins may have been caused by 

dehydration. In dogs dosed with 11 or 22 mg/kg, a slight leukocytosis was observed in animals 

showing moderate to severe signs of toxicity (Snow and Watson 1973). 

No gross or histological evidence of treatment-related damage to bone marrow or spleen was observed 

in B6C3Fl mice treated with up to 40 mg/kg/day dichlorvos by gavage for 5 days a week for 2 years 

(NTP 1989) or in Beagle dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day by capsule for 

52 weeks (AMVAC Chemical Corp. 1990). Significantly increased neoplastic lesions (leukemia) were 

observed in Fischer 344 male rats in the NTP study at doses of 4 and 8 mg/kg/day (See 

Section 2.2.2.8) 

Musculoskeletal Effects. A l0-fold increase in serum creatine phosphokinase, suggestive of 

muscle damage, was observed in a greyhound dog treated once with 11 mg/kg dichlorvos in capsules 

(Snow and Watson 1973). No gross or histological evidence of treatment-related damage to skeletal 

muscle was observed in Fischer 344 rats treated with up to 8 mg/kg/day dichlorvos by gavage 5 days 

a week for 2 years, B6C3Fl mice treated with up to 40 mg/kg/day dichlorvos by gavage for 5 days a 

week for 2 years (NTP 1989) or in Beagle dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day 

by capsule for 52 weeks (AMVAC Chemical Corp. 1990). 

Hepatic Effects. A 2-fold increase in SGFT, indicating liver damage, was observed in a 

greyhound dog treated once with 11 mg/kg dichlorvos in capsules (Snow and Watson 1973). 

Cytoplasmic vacuolization of liver cells was noted in male Fischer 344 rats receiving 4 or 8 mg/kg/day 

dichlorvos by gavage for 5 days a week for 2 years (NTP 1989). The authors stated that these 

changes were minor in extent but have been associated with lipid accumulation in cells. No gross or 

histological evidence of treatment-related damage was observed in livers from female rats or in 

B6C3Fl mice receiving 20 mg/kg/day (males) or 40 mg/kg/day (females) for 2 years in the same study 

(NTP 1989) or in Beagle dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day by capsule for 

52 weeks (AMVAC Chemical Corp. 1990). 
DICHLORVOS 48 

2. HEALTH EFFECTS 

Renal Effects. No gross or histological evidence of treatment-related damage to the kidneys was 

observed in Fischer 344 rats or B6C3Ft mice treated with dichlorvos by gavage 5 days a week for 

2 years at doses of 8 mg/kg/day (rats), 20 mg/kg/day (male mice) or 40 mg/kg/day (female mice) 

(NTP 1989) or in Beagle dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day by capsule for 

52 weeks (AMVAC Chemical Corp. 1990). 

Endocrine Effects. Cytoplasmic vacuolization of adrenal cortical cells was noted in male 

Fischer 344 rats receiving 4 or 8 mg/kg/day dichlorvos by gavage for 5 days a week for 2 years (NTP 

1989). The authors stated that these changes were minor in extent but have been associated with lipid 

accumulation in cells. Significant neoplastic lesions of the pancreas (adenomas) were also observed in 

the male rats (see Section 2.2.2.8). No increase in lesions was observed for male or female rats in the 

parathyroid, pituitary, thyroid or thymus glands. No treatment-related lesions were observed for any 

endocrine tissue in B6C3FI mice treated for 2 years at 20 mg/kg/day (males) or 40 mg/kg/day 

(females) (NTP 1989) or in Beagle dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day by 

capsule for 52 weeks (AMVAC Chemical Corp. 1990). 

Dermal Effects. No gross or histological evidence of treatment-related damage to the skin was 

observed in Fischer 344 rats or B6C3F1, mice treated with dichlorvos by gavage 5 days a week for 

2 years at doses of 8 mg/kg/day (rats), 20 mg/kg/day (male mice), or 40 mg/kg/day (female mice) 

(NTP 1989) or in Beagle dogs (groups of 4 of each sex) receiving up to 3 mg/kg/day by capsule for 

52 weeks (AMVAC Chemical Corp. 1990). 

Ocular Effects. The effect of dichlorvos on pupillary response to light has been studied in Beagles 

(Wagstaff and Winston 1980). The dogs received 0, 13.5, 27, or 40.5 mg/kg in a PVC-resin 

formulation. Dichlorvos did not affect the resting pupil and no miosis was observed. However, in 

response to a strobe light flash, dogs receiving 27 or 40.5 mg/kg had a greater contraction and a 

slower recdvery to baseline pupillary diameter. No histopathological evidence of ocular damage 

related to dichlorvos treatment was found in Beagle dogs (groups of 4 of each sex) receiving up to 

3 mg/kg/day by capsule for 52 weeks (AMVAC Chemical Corp. 1990). 

Body Weight Effects. No effects on body weight were observed in Fischer 344 rats or B6C3F1, 

mice treated with dichlorvos by gavage 5 days a week for 2 years at doses of 8 mg/kg/day (rats), 
 

 

DICHLORVOS 49 

2. HEALTH EFFECTS 

20 mg/kg/day (male mice) or 40 mg/kg/day (female mice) (NTP 1989), or in Beagle dogs (groups of 

4 of each sex) receiving up to 3 mg/kg/day by capsule for 52 weeks (AMVAC Chemical Corp. 1990). 

2.2.2.3 Immunological and Lymphoreticular Effects 

No studies regarding immunological and lymphoreticular effects were located in humans after oral 

exposure to dichlorvos. 

Immunosuppression after oral exposure to dichlorvos has been reported (Desi et al. 1978). A 

doserelated suppression of the humoral immune response induced by Salmonella typhimurium was 

observed in rabbits administered 0.3-2.5 mg/kg dichlorvos 5 days a week for 6 weeks (Desi et al. 

1978). A single oral dose of 120 mg/kg dichlorvos in male C57B l/6 mice inoculated with sheep 

erythrocytes 2 days earlier suppressed the primary IgM response observed 48 hours later (Casale et al. 

1983). A decrease in relative spleen weight was also noted in this study. Severe signs of dichlorvos 

neurotoxicity were noted, and the authors stated that the immunosuppression observed in this study 

may have been mediated indirectly by toxic chemical stress. 

In Beagle dogs treated with dichlorvos at up to 3 mg/kg/day for 52 weeks (AMVAC Chemical Corp. 

1990) no histopathologic treatment-related changes were seen in the mesenteric lymph node, spleen, 

sternum with bone marrow, and thymus. Leukocyte and reticulocyte counts were also unchanged 

compared to control, as was the leukocyte differential count. 

2.2.2.4 Neurological Effects 

Dichlorvos exerts its toxic effects in humans and animals by inhibiting neural acetylcholinesterase. 

This enzyme is present at cholinergic synapses throughout the central and peripheral nervous systems, 

and is responsible for hydrolyzing acetylcholine released from the pre-synaptic terminal. If this 

enzyme is inhibited, acetylcholine accumulates in the synaptic cleft, resulting in increased 

depolarization of the post-synaptic membrane. The consequences of this increased cholinergic activity 

in the parasympathetic autonomic nervous system can include lacrimation, perspiration, miosis, 

nausea, vomiting, diarrhea, excessive bronchial secretions, bradycardia, increased salivation, and 

increased urinary frequency and incontinence. Effects on motor nerve fibers in the skeletal muscles can 

include muscle fasciculations, cramps, muscle weakness, and paralysis. Effects on cholinergic 

synapses in the 
DICHLORVOS 50 

2. HEALTH EFFECTS 

central nervous system result in drowsiness, fatigue, mental confusion, headache, convulsions. and 

coma. These classical symptoms of organophosphate neurotoxicity increase in severity and rapidity of 

onset in a dose-dependent manner (Ecobichon 1991). 

This same enzyme is present in erythrocytes where it is known as erythrocyte acetylcholinesterase. 

Both forms of acetylcholinesterase are produced by the same gene (Taylor et al. 1993). Erythrocyte 

and neural acetylcholinesterase are inhibited to roughly the same extent by exposure to dichlorvos 

and other organophosphorus compounds (Hayes 1982); measurement of erythrocyte acetylcholinesterase is used as a surrogate of the inhibition of neural acetylcholinesterase. 

Neurological effects have been seen in many studies in animals after acute oral exposure to dichlorvos. 

Male Fischer 344 rats exposed to dichlorvos by olive oil gavage during an LD50 study had signs of 

excessive cholinergic stimulation including salivation, tremors, lacrimation, fasciculations, irregular 

respiration, and prostration (Ikeda et al. 1990). The authors did not report the dose at which these 

signs appeared; the LD50 calculated from the study was 97.5 mg/kg. In 2 other studies, in which 

clinical signs were not reported, single oral doses of 40 mg/kg dichlorvos in male rats resulted in a 

70% inhibition of brain acetylcholinesterase after one hour (Teichert et al. 1976) and an 83% 

inhibition after 15 minutes (Pachecka et al. 1977). Brain acetylcholinesterase activity was inhibited 

45% in rats receiving 4 mg/kg/day dichlorvos for 14 consecutive days (Teichert et al. 1976). 

Dichlorvos given to Fischer 344 rats by corn oil gavage 5 days a week over a l0-day period did not 

affect erythrocyte acetylcholinesterase at doses of up to 16 mg/kg/day (NTP 1989). 

Whole-body tremor in male Swiss mice was evident within 3.6 minutes after a single dose of 

150 mg/kg dichlorvos by gavage (Mohammad et al. 1989). Tremor was reported in male C57BL/6N 

mice receiving a single dose of 120 mg/kg dichlorvos by gavage (Casale et al. 1983). This clinical 

sign was accompanied by a 75% reduction in brain acetylcholinesterase activity one hour after 

dosing. In mice receiving 40 mg/kg on days 1, 3, 5, and 7, and sacrificed on day 8, significant 

reductions in acetylcholinesterase were observed in brain (30%) and erythrocytes (31%). Erythrocyte 

acetylcholin-esterase was not affected by administration of dichlorvos by gavage for 5 days a week 

over an 11-day period at doses up to 40 mg/kg in B6C3FI mice (NTP 1989). 

In greyhound dogs receiving 11 or 22 mg/kg in a single dose, signs of neurological toxicity appeared 

within 7-15 minutes of dosing (Snow and Watson 1973). Restlessness was seen initially, followed by 
DICHLORVOS 51 

2. HEALTH EFFECTS 

increased salivation. muscle fasciculations, involuntary urination, diarrhea, sometimes bloody, and 

tenesmus. There was no apparent difference in severity of clinical signs between dogs given 11 or 

22 mg/kg. Erythrocyte acetylcholinesterase was determined in 11 dogs, and the values ranged from 

69 to 97% inhibition. The dog with 97% inhibition of erythrocyte acetylcholinesterase (dosed at 

11 mg/kg) had severe clinical signs of intoxication but survived. Crossbred pigs receiving single doses 

from 18 to 560 mg/kg had clinical signs of neurological toxicity including hypoactivity, vomiting, 

ataxia, muscle fasciculations, uncoordinated movements, frothy salivation, and defecation (Stanton et 

al. 1979). 

In an intermediate-duration 21-day study in which volunteers were given dichlorvos orally, no signs of 

neurological toxicity were seen at doses of 0.033 mg/kg/day (Boyer et al. 1977). Twenty-four male 

volunteers had their serum cholinesterase and erythrocyte acetylcholinesterase determined twice a 

week for 3 weeks to establish their baseline levels. They were then given 0.9 mg dichlorvos 3 times a 

day for 21 days in either a pre-meal capsule or a 3-ounce container of gelatin. Serum cholinesterase 

and erythrocyte acetylcholinesterase were measured twice a week during the exposure period. Once a 

week, each volunteer had his vital signs measured, and was examined for tremor, pupillary response to 

light, and skin moisture. Following.the end of the study, serum cholinesterase and erythrocyte acetylcholinesterase were measured weekly for the next seven weeks. No clinical signs of neurological 

toxicity were observed in any of the volunteers. Erythrocyte acetylcholinesterase was not inhibited at 

0.033 mg/kg/day in either the gelatin or capsule formulation. Serum cholinesterase was inhibited, on 

average, 38% in the group given the pre-meal capsule and 28% in the gelatin group. Measurements 

after the dosing period showed that the half-life for regeneration of serum cholinesterase was 

13.7 days. 

In a 90-day study in female Sherman rats, groups of 10 animals were exposed to doses ranging from 

0 to 69.9 mg/kg/day in their feed (Durham et al. 1957). Two animals from each group were bled 

on days 3, 11, 60, and 90, and serum cholinesterase and erythrocyte acetylcholinesterase were 

determined. Clinical signs of neurological toxicity were not noted in any dosage group. Cholinesterase 

data was presented graphically so the percentage inhibition of the cholinesterases can only be 

estimated. For serum cholinesterase, doses of 0.4 and 1.5 mg/kg/day appeared to have no effect. 

Doses of 3.5 and 14.2 mg/kg/day appeared to produce 25-40% inhibition of enzyme activity compared 

to control values by the third day of feeding; activity remained depressed up to 60 days, and rose to 

near control values by the end of the experiment at 90 days. Serum cholinesterase in rats consuming 
DICHLORVOS 52 

2. HEALTH EFFECTS 

35.7 and 69.9 mg/kg/day fell by 50% after 3 days and remained at this level throughout the 

experiment. Erythrocyte acetylcholinesterase was unaffected at doses up to 3.5 mg/kg/day. Acetylcholinesterase activity was inhibited by 30% after 3 days at 14.2 mg/kg/day and remained depressed 

until the end of the experiment. At 35.7 and 69.9 mg/kg/day, erythrocyte acetylcholinesterase was 

inhibited about 50% after 3 days and 80% after 10 days. There appeared to be some recovery to about 

50% of control by the end of the experiment. Female Fischer 344 rats treated with dichlorvos by oral 

gavage 5 days a week for up to 32 days had no significant changes in erythrocyte acetylcholinesterase activity at doses up to 16 mg/kg/day (NTP 1989). Male rats at the same dosage levels had a 

22% decrease in erythrocyte acetylcholinesterase at day 24 at 16 mg/kg/day. 

In a similar study with B6C3F1 mice, gavage doses of dichlorvos 5 days a week up to 40 mg/kg/day 

did not affect erythrocyte acetylcholinesterase after 32 days of treatment (NTP 1989). 

Staggering gait was observed in a white Leghorn chicken receiving 6.1 mg/kg/day dichlorvos by oral 

gavage after 35 days (Francis et al. 1985). In 5 hens treated in this study with doses ranging from 

3.1 to 4.4 mg/kg/day, no adverse neurological effects were observed. 

Mild diarrhea was reported in Fischer 344 rats receiving dichlorvos at 4 and 8 mg/kg/day, 5 days a 

week for 103 weeks (NIT 1989). There were no adverse neurological effects reported in a similar 

study in male B6C3FI mice receiving up to 20 mg/kg/day or females receiving up to 40 mg/kg/day 

(NTP 1989). No gross or histopathological changes were observed in brain or sciatic nerve in any of 

the rats or mice at the end of this study (NTP 1989). 

Inhibition of erythrocyte and brain acetylcholinesterase, but no neurological signs, were reported in 

Beagles receiving 0.05, 1.0, or 3 mg/kg/day dichlorvos in capsules for 52 weeks (AMVAC Chemical 

Corp. 1990). No changes were noted at 0.05 mgkglday, but erythrocyte acetylcholinesterase was 

inhibited 45-53% in dogs receiving 1 mg/kg/day and 81-85% in dogs receiving 3 mg/kg/day. Brain 

acetylcholinesterase was inhibited 22% in male dogs receiving 1 mg/kg/day and 47% and 29%, 

respectively, in male and female dogs receiving 3 mg/kg/day. No treatment-related changes were seen 

upon histopathology review of the following neural tissues: brain with brainstem, cervical, thoracic or 

lumbar spinal cord, optic nerve, and sciatic nerve. 
 

 

DICHLORVOS 53 

2. HEALTH EFFECTS 

No studies were located in humans or animals describing OPIDN after oral exposure to dichlorvos. 

This is a syndrome observed in humans and some animal models after recovery from the acute effects 

of certain organophosphorus compounds (for example tri-o-cresyl phosphate) (Coppock et al. 1995; 

Johnson 1981). The characteristic signs are disturbances of gait, an axonalpathy or “dying-back” type 

degeneration of motor fibers. Studies on the relationship between dichlorvos and OPIDN during 

parenteral routes of exposure are discussed in Section 2.5. 

All reliable NOAELs and LOAELs for neurological effects in each species and duration category are 

recorded in Table 2-2 and plotted in Figure 2-2. 

2.2.2.5 Reproductive Effects 

No studies were located regarding reproductive toxicity in humans after oral exposure to dichlorvos. 

Maternal toxicity was not reported in CF-1 mice treated by gavage with 60 mg/kg/day dichlorvos 

during gestation days 6-15 or in New Zealand rabbits treated by gavage with 5 mg/kg/day (Schwetz et 

al. 1979). Microscopic examination of male reproductive tissues (prostate, testes, epididymis) and 

female reproductive tissues (ovaries, uterus) revealed no changes attributable to oral dichlorvos 

exposure during 2-year studies in Fischer 344/N rats treated at 4 or 8 mg/kg/day for 5 days a week or 

B6C3F1 mice (males treated at 10 or 20 mg/kg/day, females at 20 or 40 mg/kg/day) (NTP 1989). 

Similar results were obtained in Beagle dogs receiving dichlorvos by capsule for 52 weeks at up to 

3 mg/kg/day (AMVAC Chemical Corp. 1990). Male reproductive tissues examined were the testes, 

prostate, and epididymides; female tissues examined were the cervix, ovaries, uterus, and vagina. 

2.2.2.6 Developmental Effects 

No studies were located regarding developmental toxicity in humans after oral exposure to dichlorvos. 

No adverse developmental effects were observed in CF-1 mice treated by gavage with 60 mg/kg/day 

dichlorvos during gestation days 6-15 (Schwetz et al. 1979). There was no significant effect on 

implantations, mean number of fetuses per litter, incidence or distribution of resorptions, or on fetal 

body measurements. Similar results were observed in New Zealand rabbits treated by gavage with 

5 mg/kg/day over gestation days 6-18 (Schwetz et al. 1979). 
 

 

DICHLORVOS 54 

2. HEALTH EFFECTS 

Pregnant crossbred sows given PVC-resin formulations of dichlorvos in the diet at a daily dose of 0, 5, 

or 25 mg/kg during the last 30 days of pregnancy had 100% live births and birth weights similar to 

control animals (Stanton et al. 1979). There are a number of reports on dichlorvos treatment of 

pregnant sows causing a dose-related increase in percentage of live births, mean birth weights and 

weaning weights. The mechanism of action for this phenomenon has not been established (Gallo and 

Lawryk 1991). 

2.2.2.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.5. 

2.2.2.8 Cancer 

No studies were located regarding cancer in humans after oral exposure to dichlorvos. 

In a carcinogenicity study in Osborne-Mendel rats, groups of 50 animals of each sex were originally 

dosed through feed at levels of 45 and 90 mg/kg/day. Ten animals of each sex were used as controls 

and were pooled with 50 other control rats of each sex from studies conducted concurrently on 5 other 

compounds (NCI 1977). During the initial 3 weeks of dosage, acute signs of toxicity were observed, 

including tremor and diarrhea in the 90-mg/kg/day group. Therefore, the dosages were then lowered 

to 30% of the original. The time-weighted average (TWA) doses over the 80-week period of dosing 

were 13.5 and 29.3 mg/kg/day. After the go-week dosing period, the animals were observed for a 

further 30 weeks until sacrifice. Gross necropsy was done on all animals that died during the study 

and at termination. Microscopic examination was done on sections of brain, pituitary, adrenal, thyroid, 

parathyroid, trachea, esophagus, thymus, salivary gland, lymph nodes, heart, lung, spleen, liver, 

kidney, stomach, pancreas, small intestine, large intestine, urinary bladder, prostate or uterus, testis or 

ovary, mammary gland, skin, and bone, including marrow. Adverse clinical signs (hematuria, rough 

coats, epistaxis) were noted in control and dosed animals gradually increasing during the second year 

of the study. The authors stated that at the end of the study, the rats (i.e., both treated and control) were 

in generally poor condition. The matched control groups had significantly lower survival than the 

treated groups at the end of the study, mainly due to deaths during the 30-week observation period 

after treatment (NCI 1977). At the end of the study, only 2 of 10 male rats and 5 of 10 female rats 

survived in the matched control groups. For this reason, these control rats were pooled with control 
DICHLORVOS 55 

2. HEALTH EFFECTS 

rats from concurrent studies for comparison with the treated groups. Of the male rats, 76% of the 

high-dose and 64% of the low-dose group survived to the end of the study, as did 84% of the highdose 

and 80% of the low-dose females. 

Many inflammatory, degenerative, and proliferative lesions commonly seen in aged rats occurred with 

approximately equal frequency in treated and the pooled control rats (NCI 1977). Several 

nonneoplastic lesions occurred more frequently in the treated rats than in the controls. These included 

aggregates of alveolar macrophages in the lungs, interstitial fibrosis of the myocardium, and focal 

follicular cell hyperplasia in the male rats. Benign endocrine neoplasms occurred frequently in both 

test and control rats. There was a high incidence of benign mammary neoplasms in both control and 

treated rats. Because of the low survival of the matched control rats, control animals from other 

concurrent studies were pooled for statistical analysis. The authors stated that on the basis of 

variability of both the incidence and type of spontaneous lesions, and the lack of significant 

proportions of tumors in the dosed groups compared to the controls, no statistical significance could be 

attached to the incidence of tumors seen in the dichlorvos-treated rats in this study. Because of the 

poor survival of control animals in this study, the results are difficult to interpret. Dichlorvos was 

subsequently re-tested by the National Toxicology Program (NTP 1989). 

In another carcinogenicity study in rats, groups of 50 Fischer 344 rats of each sex were dosed with 

dichlorvos in corn oil by oral gavage at levels of 0, 4, or 8 mg dichlorvos for 5 days a week for 

103 weeks (NTP 1989). Necropsy and histopathologic examinations were performed on all animals at 

the end of the study or at the time of death. Histopathology was done on the following tissues: 

adrenal gland, brain, cecum, colon, duodenum, esophagus, femur including marrow, heart, ileum, 

jejunum, kidneys, liver, lungs and mainstem bronchi, mammary glands, mandibular and mesenteric 

lymph nodes, nasal cavity and turbinates, pancreas, parathyroid glands, pituitary gland, preputial or 

clitoral gland, prostate/testes/epididymis or ovaries/uterus, rectum, salivary glands, sciatic nerve, skin, 

spleen, stomach, thymus, thyroid gland, tissue masses, trachea, and urinary bladder. No significant 

differences in survival were noted between any groups. Survival rates were: 31 of 50-for male and 

female controls; 25 of 50 males and 26 of 50 females in the low-dose group; and 24 of 50 males and 

26 of 50 females in the high-dose group. 

Statistically significant increases in neoplasms compared to control animals were observed in the 

pancreas and hematopoietic system in male rats and in the mammary gland in female rats in this study 
DICHLORVOS 56 

2. HEALTH EFFECTS 

(NTP 1989). Adenoma of the exocrine pancreas exhibited a significant positive trend, and the 

incidences were greater in treated as compared to control groups (16 of 50 in vehicle control, 25 of 

49 in the low-dose group and 30 of 50 in the high-dose group). When horizontal sections of the 

pancreas were examined, additional adenomas were observed. When the data from both methods were 

combined, the incidences of pancreatic adenoma were 25 of 50 in the controls, 30 of 49 in the lowdose group, and 33 of 50 in the high-dose group. The incidence for the treated groups was 

statistically significant compared to the vehicle controls. 

A significant positive trend (i.e., not dose related) for mononuclear cell leukemia was also observed in 

the male rats. This neoplasm was found in 11 of 50 controls, 20 of 50 in the low-dose group, and 

21 of 50 in the high-dose group. A significant positive trend also occurred for mammary gland tumors 

in female rats. Fibroadenoma, adenoma, or carcinoma occurred in 9 of 50 control rats, 19 of 50 in the 

low-dose group, and 17 of 50 in the high-dose group. Peer review panels characterized these results 

as “some evidence” of carcinogenic activity in male rats and “equivocal evidence” in female rats. 

Dichlorvos has also been tested for carcinogenicity in two long-term studies on B6C3Fl mice (NCI 

1977; NTP 1989). Using the same protocol as the NCI (1977) study described above for OsbomeMendel rats, groups of 50 male and 50 female B6C3F1 rats were fed dichlorvos in the diet at doses of 

57 or 114 mg/kg/day for 80 weeks followed by a 14-week observation period before sacrifice (NCI 

1977). These doses were converted from the originally reported dichlorvos-in-feed doses (318 and 

635 ppm) by conversion factors for average mouse daily feed consumption (EPA 1988). Groups of 

10 male and 10 female mice served as matched controls. The same tissues were examined 

histologically as in the Osborne-Mendel rat study described above. Two squamous-cell carcinomas of 

the esophagus (in one low-dose male and one high-dose female) and one papilloma of the esophagus 

in a high-dose female were seen. The authors stated that these were historically very rare lesions in 

this strain of mice. Focal hyperplasia of the esophageal epithelium was also seen in three low-dose 

males. However, no statistically significant differences in neoplastic lesions were seen due to 

treatment. 

Dichlorvos was also tested for carcinogenicity in male and female B6C3Fl mice by a protocol similar 

to that used on the Fischer 344 rats described above (NTP 1989). Because of higher toxicity in male 

mice during the dose-finding study, groups of 50 male mice were dosed by corn oil gavage at 0, 10, or 

20 mg/kg for 5 days a week, while the female groups were dosed at 0, 20, or 40 mg/kg for 5 days a 
DICHLORVOS 57 

2. HEALTH EFFECTS 

week. Necropsy and histopathologic examinations were performed on all animals at the end of the 

study (102 weeks) or at the time of death. The same tissues were examined as in the Fischer 344 rat 

study described above. 

The only neoplasms that occurred with a significant positive trend in treated compared to control mice 

were squamous cell papilloma and carcinomas of the forestomach. The overall incidences of this 

lesion in male mice were 1 of 50 in the controls, 1 of 50 in the low-dose group, and 5 of 50 in the 

high-dose group. In the females, overall incidences were 5 of 49 in the control group, 6 of 49 in the 

low-dose group and 18 of 50 in the high-dose group. Incidence was near the historical incidence of 

1% in male controls, but was higher in the female controls (10% compared to 1%). Peer review 

panels characterized the level of carcinogenic activity as “some evidence” in male mice and “clear 

evidence” in female mice. 

2.2.3 Dermal Exposure 

2.2.3.1 Death 

Two workers in Costa Rica died after splashing a concentrated formulation of dichlorvos on their bare 

arms and failing to wash it off promptly (Hayes 1982). Information on the concentration of dichlorvos 

in the concentrate was not available. 

Three cynomolgus monkeys were given daily dermal doses of dichlorvos in xylene on a shaved area 

between the shoulder blades (Durham et al. 1957). A monkey receiving 100 mg/kg/day died after 

4 days. A monkey given 50 mg/kgl/day died after 8 doses over 10 days and a monkey given 

75 mg/kg/day died after 10 doses over 12 days. Clinical signs occurred within 10-20 minutes after 

dosing. Signs in their order of appearance were nervousness, gritting of teeth, incoordination, muscle 

fasciculations, excessive salivation, labored breathing, miosis, and flaccidity. 

In an LD50 study in Sherman rats where dichlorvos in xylene was applied to an area of clipped skin 

between the shoulder blades (Durham et al. 1957), the dermal LD50 was 107 mg/kg for male rats and 

75 mg/kg for females. All rats killed by a single dermal dose died within 20 minutes of dosage, 

except a male dosed at 110 mg/kg that survived for 40 minutes and another male dosed at 125 mg/kg 

that survived for 17 days. The symptoms of poisoning observed were bulging eyes, lacrimation, 
 

DICHLORVOS 58 

2. HEALTH EFFECTS 

sialorrhea, muscle fasciculations, and tremors. Some animals had convulsions just before death. Rats 

that survived appeared to make a full recovery. In another LD50, study where dichlorvos was applied 

to female Wistar rats in ethanol-water on depilated skin, an LD50 of 70.4 mg dichlorvos was found 

(Gajewski and Katkiewicz 1981). Two white Leghorn chickens dosed daily on the ventral wing 

surface at the humerus with 14.4 and 15.7 mg/kg in an emulsion containing xylene and 2% Triton 

X-100 died after 2 and 3 doses, respectively (Francis et al. 1985). Five of 9 hens in this study 

receiving 0.54-3.8 mg/kg/day dichlorvos died between 30 and 45 days after the beginning of dosing. 

The lowest dose resulting in death was 1.7 mg/kg/day after 36 days. 

All reliable LOAELs for death are recorded in Table 2-3. 

2.2.3.2 Systemic Effects 

No studies regarding systemic effects in humans after dermal exposure were located except for dermal 

effects. No studies regarding systemic effects in animals were located except for respiratory, dermal 

and ocular effects. 

The LOAELs for systemic effects are recorded in Table 2-3. 

Respiratory Effects. Labored breathing was observed in 3 cynomolgus monkeys receiving daily 

dermal doses of 50, 75, or 100 mg/kg/day (Durham et al. 1957). The authors stated that these and 

other cholinergic signs occurred within 10-20 minutes of dosing. 

Dermal Effects. A 52-year-old male truck driver who had been hauling pesticide containers 

presented with dermatitis of his neck, anterior chest, dorsal hands, and forearms (Mathias 1983). On 

the previous day, several containers spilled in his truck, and he apparently had direct dermal contact 

with a pesticide containing 5% dichlorvos, 15% petroleum distillates, and 80% trichloroethane. A 

faint papular dermatitis was present over the dorsal arms, hands, and V of the neck. .Vertical 

erythematous, slightly scaling streaks were present over the lateral and posterior neck, a pattern 

suggesting that liquid droplets had produced the dermatitis. The dermatitis was treated with 1% 

hydrocortisone ointment. Follow-up examination six weeks later showed persistent vertical, mildly 

erythematous streaks over the posterior and lateral neck; the arms and anterior chest had cleared. 


 

 

DICHLORVOS 61 

2. HEALTH EFFECTS 

Negative patch test results suggested that the dermatitis resulted from a primary irritant effect of 

dichlorvos on the skin. Dermatitis resolved completely approximately 10 weeks after onset. The 

persistence of dermatitis 2 months after exposure is very unusual, and the author suggested that this 

may be related to some unique local toxic effect of dichlorvos, but did not speculate further. 

As part of a study on the ability of dichlorvos to cause sensitization in a guinea pig maximization test 

(Ueda et al. 1994), the threshold irritation concentration of dichlorvos on guinea pig skin was reported 

to be 1%. No further details were given. 

Ocular Effects. Miosis was observed in cynomolgus monkeys receiving daily dermal doses of 50, 

75, or 100 mg/kg/day (Durham et al. 1957). It was not reported whether this resolved before the next 

daily dose. This sign is related to the cholinergic overstimulation caused by dichlorvos. 

2.2.3.3 Immunological and Lymphoreticular Effects 

Six of 59 males and 9 of 48 females in an occupational study of flower growers showed positive 

reactions on patch testing to dichlorvos for an overall rate of 14%. Twelve of 18 subjects who had 

positive skin patch test reactions to triforine (1,4-bis [2,2,2-trichlor- 1-formamidoethyl] piperazine) 

also showed positive reactions to dichlorvos (Ueda et al. 1994). These subjects may have also been 

occupationally exposed to dichlorvos. 

In a guinea pig maximization test conducted in this study, induction with dichlorvos by intradermal 

injection and topical application and subsequent challenge with topical dichlorvos solutions showed 

sensitization (Ueda et al. 1994). Cross-reactivity with dichlorvos was demonstrated in animals induced 

with triforine. 

2.2.3.4 Neurological Effects 

Dichlorvos exerts its toxic effects in humans and animals by inhibiting neural acetylcholinesterase. 

This enzyme is present at cholinergic synapses throughout the central and peripheral nervous systems 

and is responsible for hydrolyzing acetylcholine released from the pre-synaptic terminal. If this 

enzyme is inhibited, acetylcholine accumulates in the synapse, resulting in increased firing of the 

postsynaptic neuron or increased contractions in muscle. The consequences of this increased 

cholinergic 
DICHLORVOS 62 

2. HEALTH EFFECTS 

activity in the parasympathetic autonomic nervous system can include lacrimation, perspiration. 

miosis, nausea, vomiting, diarrhea, excessive bronchial secretions, bradycardia, increased salivation, 

and increased urinary frequency and incontinence. Effects on motor nerve fibers in the skeletal 

muscles can include muscle fasciculations, cramps, muscle weakness and flaccidity. Effects on 

cholinergic synapses in the central nervous system result in drowsiness, fatigue, mental confusion, 

headache, convulsions and coma (Ecobichon 1991). 

This same enzyme is present in erythrocytes where it is known as erythrocyte acetylcholinesterase. 

Both forms of acetylcholinesterase are produced by the same gene (Taylor et al. 1993). Erythrocyte 

and neural acetylcholinesterase are inhibited to roughly the same extent by exposure to dichlorvos 

and other organophosphorus compounds; measurement of erythrocyte acetylcholinesterase is used as 

an indicator of inhibition of neural acetylcholinesterase (Hayes 1982). 

A truck driver who had direct skin contact with a pesticide solution containing dichlorvos developed 

dermatitis and also complained of headache, mild rhinorrhea, a burning sensation on his tongue and a 

bitter taste in his mouth the day after exposure occurred (Mathias 1983). He was exposed to a 

solution containing 5% dichlorvos, 15% petroleum distillates, and 80% trichloroethane. Initial blood 

cholinesterase determination (specific enzyme not specified) were in the low-normal range and had 

risen to the high-normal range two weeks later. 

Three cynomolgus monkeys were exposed to dichlorvos dissolved in xylene by daily derrnal doses on 

a shaved area between the shoulder blades (Durham et al. 1957); cholinergic signs appeared within 

10-20 minutes of dosage. Signs of toxicity in order of appearance were: nervousness, incoordination, 

muscle fasciculations, excessive salivation, labored breathing, miosis, and inability to move. The 

authors stated that at a given dose, the cholinergic signs tended to become more severe with 

subsequent doses. Serum cholinesterase and erythrocyte acetylcholinesterase were measured in one 

monkey that received 75 mg/kg/day. After 2 doses, erythrocyte acetylcholinesterase had declined 

about 67%, while serum cholinesterase was unchanged. When these values were measured shortly 

after the next day’s dosage, the serum cholinesterase had fallen about 33%, while erythrocyte acetylcholinesterase remained inhibited about 67%. The serum cholinesterase recovered after 2 days 

without dosing, but the erythrocyte acetylcholinesterase did not. After 5 doses, the erythrocyte acetylcholinesterase had fallen by 90% and stayed there until death occurred after 12 days, during which 10 

doses were administered. 
DICHLORVOS 63 

2. HEALTH EFFECTS 

Signs of neurological toxicity were also observed in Sherman rats dermally exposed to dichlorvos 

during an LD50 experiment (Durham et al. 1957). Rats that survived exhibited bulging eyes, excessive 

lacrimation, and generalized muscle fasciculation and tremors. Surviving rats appeared to completely 

recover after 24 hours. 

In a study involving daily dermal administration of dichlorvos in white Leghorn chickens, 3 hens 

receiving 2.8-3.8 mg/kg/day exhibited a staggering gait after 14 days of treatment (Francis et al. 

1985). Three hens receiving doses between 0.54 and 0.71 mg/kg/day showed no signs of abnormal 

gait over 90 days of dosing. 

In a study designed to determine the optimal configuration of skin patches for delivery of dichlorvos 

as a potential therapy for Alzheimer’s disease (Moriearty et al. 1993), dichlorvos was dissolved in 

mineral oil or olive oil and applied in 10-mg doses (34 mg/cm2

/kg). Groups of three male SpragueDawley rats received patches of different materials taped in place on the shaved intracapsular area. At 

one and 7 days after administration, rats were sacrificed and brain acetylcholinesterase, serum 

cholinesterase and erythrocyte acetylcholinesterase were measured. Brain acetylcholinesterase 

inhibition after 24 hours ranged from 47.5% in the olive oil patches to 67.4% in the mineral oil 

patches. Brain acetylcholinesterase inhibition persisted for seven days. An experiment delivering 4 

different doses of dichlorvos over a l0-fold range showed a linear log-dose relationship for inhibition 

of brain acetylcholinesterase. Erythrocyte acetylcholinesterase was not reported, although the 

authors said it was “similar” to the inhibition seen in brain. Serum cholinesterase inhibition peaked on 

the first day (approximately 60%), and returned to normal by the seventh day. No clinical signs of 

toxicity were reported. 

No studies were located in humans or animals describing OPIDN after dermal exposure to dichlorvos. 

This is a syndrome observed in humans and some animal models after recovery from the acute effects 

of certain organophosphorus compounds, for example tri-o-cresyl phosphate (Coppock et al. 1995; 

Johnson 1981). The characteristic signs are disturbances of gait, a “dying-back” type degeneration of 

motor fibers. Studies on the relationship between dichlorvos and OPIDN during parenteral routes of 

exposure are discussed in Section 2.5. 

The LOAELs for neurological effects are recorded in Table 2-3. 

DICHLORVOS

2. HEALTH EFFECTS 

 64 
 

 

 

 

 64 

2.3 

DICHLORVOS

2. HEALTH EFFECTS 

No studies were located regarding the following effects in humans or animals after dermal exposure to 

dichlorvos: 

2.2.3.5 Reproductive Effects 

2.2.3.6 Developmental Effects 

2.2.3.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.5. 

2.2.3.8 Cancer 

No studies regarding cancer in humans or animals after dermal exposure to dichlorvos were located. 

TOXICOKINETICS 

Dichlorvos is a small, lipid-soluble molecule that can be absorbed by passive diffusion through the 

lungs, gastrointestinal tract, or skin. Little information is available on how rapidly dichlorvos is 

absorbed during inhalation exposure, but it appears to be rapidly absorbed by the oral and dermal 

routes of exposure. Because of the difficulty in assaying dichlorvos in biological tissues, this rapid 

rate of absorption is inferred from the time to onset of clinical signs and/or cholinesterase inhibition. 

This is due to the rapid degradation of dichlorvos by tissue esterases, particularly in the liver and the 

serum. The half-life of dichlorvos in human blood in vitro is about 10 minutes (Blair et al. 1975). 

Distribution is also difficult to study because of rapid metabolism, but there does not appear to be 

preferential distribution to particular tissues. Dichlorvos does not appear to be stored or concentrated 

in any tissue. The products of the esterase-catalyzed degradation of dichlorvos are dimethyl phosphate 

and dichloroacetaldehyde. Dimethyl phosphate is excreted in the urine, while dichloroacetaldehyde 

can be reduced to dichloroethanol or dehalogenated to glyoxal, which enters 2-carbon metabolism. 

Dichloroethanol is either conjugated to glucuronic acid and excreted in the urine or dehalogenated and 

further metabolized. There is also evidence that dichlorvos can be demethylated in a glutathionedependent reaction. The target for the toxicity of dichlorvos is neural acetylcholinesterase in the 

central and peripheral nervous systems. Dichlorvos chemically reacts with this enzyme’s active site 
 

DICHLORVOS 65 

2. HEALTH EFFECTS 

and inhibits enzyme activity. None of the metabolites of dichlorvos inhibit neural acetylcholinesterase activity. Reported kinetic parameters for dichlorvos are listed in Table 2-4. 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

Indirect evidence for absorption of dichlorvos following inhalation in humans was obtained by 

measuring dichloroethanol, a specific dichlorvos metabolite, in the urine of a male volunteer (Hutson 

and Hoadley 1972b). This individual was exposed at the extremely high level of 38 mg/m3 (4.2 ppm) 

for 105 minutes. The first urine sample obtained after exposure ended was analyzed by gas-liquid 

chromatography and 0.42 μg dichloroethanol/mL urine was detected (Hutson and Hoadley 1972b). 

The dichlorvos metabolite dimethyl phosphate was found in the urine of 3 of 13 male volunteer 

pesticide applicators who applied dichlorvos during an 8hour workday (Das et al. 1983). During the 

application, they wore goggles, caps, respirators, coats, gloves, and shoes. Each applicator sprayed 

4 homes using 10-14 aerosol cans (230-330 g dichlorvos) and 18-22 pints of 0.5% emulsion spray 

(40-50 g dichlorvos). A range of 0.32-l .39 μg of dimethyl phosphate was measured in the urine of 

3 workers. No effect was seen in clinical parameters or plasma cholinesterase activities. Dichlorvos 

was not detected (detection limit was 1 μg/g) in the blood of 2 male volunteers immediately after 

exposure to air concentrations of 0.25 mg/m3

 (0.03 ppm) for 10 hours or to 0.7 mg/m3 (0.08 ppm) for 

20 hours (Blair et al. 1975). Low-level exposure and breakdown by esterases may account for 

nondetection of dichlorvos. 

In Sherman rats exposed to air saturated with dichlorvos (approximately 33 ppm), clinical signs of 

cholinergic stimulation were observed within 2 hours, showing that absorption had taken place 

(Durham et al. 1957). Intact dichlorvos was detected in rats after inhalation only at very high 

atmospheric levels. Thus, 0.07 and 0.08 μg/g could only be detected in the kidney of 2 of 3 male rats 

exposed for 4 hours to 10 mg/m3

 (1.1 ppm) (Blair et al. 1975). Similarly, dichlorvos was detected in 

all the tissues tested in the male mice and in blood, fat, and lungs of 3 female mice exposed for 

4 hours to 90 mg/m3 (10 ppm) (Blair et al. 1975). Neither dichlorvos nor desmethyl dichlorvos was 

detected in tissues of 3 young pigs (20 kg; 1 female, 2 males) that were exposed to 1-14Cvinylldichlorvos (0.092 mg/m3

 for the female, and 0.114 mg/m3 for the males) for 23 hours a day for 

 

 

DICHLORVOS 67 

2. HEALTH EFFECTS 

24 days (detection limit 3 ng/g) (Loeffler et al. 1976). Total radioactivity expressed as ppm dichlorvos 

equivalent in tissues ranged from 0.2 to 0.4 ppm in brain and subcutaneous fat to 2.4-2.6 ppm in liver. 

2.3.1.2 Oral Exposure 

When 5 mg [vinyl-14C]dichlorvos was ingested in orange juice by a male volunteer, 27% of the dose 

was recovered from expired air as 14CO, (Hutson and Hoadley 1972b). Dichlorvos was detected 

(0.18 mg/L) in the blood of fetuses 5 minutes after oral administration of 6 mg/kg dichlorvos in 

sunflower oil to 5 pregnant rabbits on the day of delivery (Maslinska et al. 1979). A total of 38.2% of 

the [ l-14C-vinyl]dichlorvos (40 mg/kg in PVC pellets) was absorbed in 9 young male Yorkshire pigs 

(Potter et al. 1973a), the remainder was recovered in the pellets. In another experiment, where [l-14Cvinylldichlorvos was mixed with feed, absorption of dichlorvos was demonstrated by the recovery of 

4% of the radioactivity in the urine, 5% in the feces, and 6.6% in the expired air (Potter et al. 1973b). 

Small amounts (ppb) of organosoluble [32P] (presumably dichlorvos or desmethyl dichlorvos) was 

detected in the milk of a lactating cow after the oral administration of 1 mg/kg/day [32P]dichlorvos for 

7 days followed by a dose of 20 mg/kg on day 8 in gelatin capsules (Casida et al. 1962). Dichlorvos 

was effectively absorbed in 6 male and 6 female rats following the oral administration of 3.6 mg/kg 

[methyl-14C]dichlorvos in arachis oil as indicated by the recovery of 64.6% of the dose in urine 

(Hutson and Hoadley 1972a). Identical recovery was obtained in 6 male and 6 female mice given 

22 mg/kg [methyl-14C]dichlorvos (Hutson and Hoadley 1972a). When [vinyl-14C]dichlorvos was 

administered orally to 2 male Syrian hamsters at a dose of 3.7 mg/kg and to a female at a dose of 

1.5 mg/kg, it was rapidly absorbed and 11.9-21.8% of the dose was recovered in the urine. 

Evidence for rapid absorption of dichlorvos by the oral route includes death of Swiss mice within 

9 minutes after a single gavage dose of 150 mg/kg (Mohammad et al. 1989) and in crossbred swine 

within 15-30 minutes receiving 100-560 mg/kg in an LD50 study (Stanton et al. 1979). Signs of 

cholinergic toxicity (vomiting, diarrhea) were observed in greyhound dogs within 7-15 minutes of 

receiving 11 mg/kg dichlorvos by gelatin capsule (Snow and Watson 1973). 

2.3.1.3 Dermal Exposure 

Dichlorvos appears to be rapidly absorbed by dermal exposure, although absorption by this route has 

not been well characterized. Monkeys exposed dermally to dichlorvos in xylene solution at doses of 
 

DICHLORVOS 68 

2. HEALTH EFFECTS 

50, 75, or 100 mg/kg exhibited signs of neurotoxicity within 15-20 minutes of administration, 

indicating rapid absorption (Durham et al. 1957). Similar results were seen in Sherman rats during an 

LD50, study (LD50s were 107 mg/kg for males and 75 mg/kg for females). In this study, all rats that 

died did so within 20 minutes (Durham et al. 1957). 

2.3.2 Distribution 

2.3.2.1 Inhalation Exposure 

Inhalation exposure of rats and mice to a concentration of 90 mg/m3 (10 ppm) dichlorvos in air for 

4 hours produced mild signs of toxicity such as lethargy and pupil constriction (Blair et al. 1975). 

Dichlorvos concentrations were very low or undetectable in blood (<0.2 mg/kg), liver, testes, lung, and 

brain (<0.1 mg/kg) of rats. In contrast, kidneys and fat contained concentrations as high as 2.4 and 

0.4 mg/kg tissue, respectively. In rats, dichlorvos seemed to have been trapped in the trachea as 

indicated by its higher concentration in the trachea compared to lungs. When rats were exposed for 

4 hours to 10 mg/m3

 (1.1 ppm) in air, only the kidneys of the male animals contained detectable or 

measurable concentrations (0.08 mg/kg). The results in mice were different from rats, the mice having 

higher concentrations of dichlorvos in fat, lung, and testes, but much lower concentrations in the 

kidneys. No residues (<0.00l mg/kg) of dichlorvos were detected in blood, liver, kidney, renal fat, or 

lung tissues of rats exposed to 0.5 or 0.05 mg/m3 (0.06 or 0.006 ppm) for 14 days. On the other 

hand, exposure of male rats to 50 mg/m3 (6 ppm) resulted in detectable dichlorvos (1.7 mg/kg) in the 

kidneys after 2 and 4 hours exposure time. On removal of rats from exposure, the concentration of 

dichlorvos in the kidneys decreased rapidly with an estimated half-life of 13.5 minutes. Dichlorvos 

disappeared from the blood within 15 minutes after exposure (Blair et al. 1975). 

Neither dichlorvos nor its metabolite desmethyl dichlorvos was detected in pigs exposed to 

0.092 mg/m3

 (0.01 ppm) for 23 hours a day for 24 days. When young pigs were exposed for 24 days 

via inhalation to 0.15 mg/m3

 [l-14C-vinyl]dichlorvos, radioactivity was detected in various tissues 

(blood, liver, lungs), but no intact dichlorvos was detected (Loeffler et al. 1976). 
 

 

 

DICHLORVOS 69 

2. HEALTH EFFECTS 

2.3.2.2 Oral Exposure 

Little information is available on the distribution of dichlorvos after oral administration. It is probable 

that a large “first-pass effect” takes place in the liver when dichlorvos is absorbed from the 

gastrointestinal tract (Gaines et al. 1966). This may reduce intact dichlorvos concentrations below 

detection limits in tissues. Dichlorvos (0.18 mg/L) appeared in the blood of fetuses 5 minutes after 

oral administration of 6 mg/kg dichlorvos in sunflower oil to pregnant rabbits on the day of delivery 

(Maslinska et al. 1979). Organosoluble [32P] (presumably dichlorvos or desmethyl dichlorvos) was 

detected in the milk of a lactating cow 30 minutes after oral administration of 

1 mg/kg/day [32P]dichlorvos for 7 days followed by a dose of 20 mg/kg on day 8 in gelatin capsules 

(Casida et al. 1962). 

2.3.2.3 Dermal Exposure 

No information was located on tissue distribution after dermal exposure to dichlorvos. 

2.3.3 Metabolism 

In viva and in vitro studies have established the liver as the major site of dichlorvos detoxification 

(Casida et al. 1962; Gaines et al. 1966). Other tissues also metabolize dichlorvos in vitro; 

[

32P]dichlorvos was metabolized by blood, adrenal, kidney, lung and spleen tissue mostly to dimethyl 

phosphate. Other metabolites found were desmethyl dichlorvos, monomethyl phosphate, and inorganic 

phosphate (Loeffler et al. 1976). Pathways of metabolism for .dichlorvos are shown in Figure 2-3. 

Metabolism studies of dichlorvos have been carried out in several animal species including human 

beings (Hutson and Hoadley 1972b), rats (Casida et al. 1962; Hutson and, Hoadley 1972a; Hutson et 

al. 1971), mice (Hutson and Hoadley 1972a, 1972b), Syrian hamsters (Hutson and Hoadley 1972b), 

pigs (Loeffler et al. 1976; Potter et al. 1973a, 1973b), goats (Casida et al. 1962), and cows (Casida et 

al. 1962) using radiolabeled dichlorvos and various routes of administration. These studies have 

shown that dichlorvos metabolism is generally similar in different species. Differences among species 

are mostly quantitative and related to the rate of metabolic pathways. 

DICHLORVOS 71 

2. HEALTH EFFECTS 

Dichlorvos breaks down via two enzymatic mechanisms. The first is glutathione-independent, 

catalyzed by “A”-type esterases, and produces dimethyl phosphate and dichloroacetaldehyde (Wright 

et al. 1979). The second is glutathione-dependent and results in formation of desmethyl dichlorvos and 

S-methyl glutathione (see Figure 2-3). Subsequent degradation of desmethyl dichlorvos to 

dichloroacetaldehyde and monomethyl phosphate is also catalyzed by “A”-type esterases (Wright et al. 

1979). S-methyl-glutathione is broken down to methylmercapturic acid and excreted in the urine of 

animals treated with dichlorvos. 

Several in vitro studies have examined the metabolism of dichlorvos in blood. An “A”-type esterase 

activity distinct from paraoxonase has been characterized in human serum (Traverso et al. 1989). A 

Km of 7.1 mM was reported for the degradation of dichlorvos and a Vmax of 143 nmol/min/mL. A 

Km of 4 mM has also been reported in human serum for dichlorvos (Reiner et al. 1980). Half-times 

for degradation of dichlorvos in whole blood were 8.1 minutes for human males and 11.2 minutes for 

human females (Blair et al. 1975). 

The vinyl moiety of the dichlorvos molecule undergoes two routes of biotransformation: conversion to 

dichloroethanol and subsequent formation of dichloroethanol glucuronide; or dehalogenation and 

incorporation of the carbon atoms into various metabolic pathways in the body. These pathways result 

in the production of hippuric acid, urea, carbon dioxide, and other endogenous compounds that result 

in a prolonged half-life of radioactivity in the tissues following the administration of [vinyl14C]dichlorvos. Both radiolabelled dichloroethanol glucuronide and urea have been identified in the 

urine of men treated with [vinyl-14C]dichlorvos indicating that both pathways occur in humans 

(Hutson and Hoadley 1972b). In other animal species, most of the radioactivity in carcasses and 

tissues was identified as glycine, serine, and other body compounds resulting from the metabolism of 

the vinyl carbon atoms (Hutson and Hoadley 1972b; Loeffler et al. 1976). Neither dichlorvos nor its 

metabolites accumulated in any tissues of animals treated with dichlorvos. 

The metabolism of some dichlorvos metabolites has been studied in experimental animals. Most of 

the single oral dose of 500 mg of [32P]dimethylphosphate/kg body weight in rats was eliminated, with 

urine containing about 50% unmetabolized dimethylphosphate (Casida et al. 1962). On the other hand, 

when a single oral dose of 500 mg [32P]desmethyl dichlorvos was administered to rats, 14% of the 

dose was recovered in the urine in 90 hours, with 86% of the radioactivity identified as phosphoric 

acid and 14% as unchanged desmethyl dichlorvos. The bone contained a high proportion of 
DICHLORVOS 72 

2. HEALTH EFFECTS 

radioactivity suggesting the incorporation of the phosphoric acid that was produced via rapid complete 

degradation of dichlorvos (Casida et al. 1962). Also, female rats given an intraperitoneal injection of 

[1-14C]dichloroacetaldehyde excreted 32% of the radioactivity in expired air as carbon dioxide within 

24 hours (Casida et al. 1962). 

2.3.4 Elimination and Excretion 

Following a single oral dose of 5 mg/kg body weight [14C]dichlorvos in a human male, 27% of the 

radioactivity was eliminated as 14CO2, while only 9% of the radioactivity was eliminated in the urine, 

Radioactivity excreted in urine decreased with time and none was detected by day nine (Hutson and 

Hoadley 1972b). 

Rats given a single oral dose of 0.1-80 mg/kg body weight [32P]dichlorvos excreted 66-70% of the 

dose in the urine and approximately 10% in the feces during a 6-day period after dosing (Casida et al. 

1962). After a single oral dose of 1 mg (rats) or 0.5 mg (mice) [methyl-14C]dichlorvos in 0.5 mL of 

arachis oil, approximately 65% of the radioactivity was eliminated in the urine, while only 15% was 

recovered in the expired air over the following 4 days (Hutson and Hoadley 1972a). Following the 

administration of a single oral dose of 20 mg [32P]dichlorvos to a cow, 40% of the dose was 

eliminated in the urine and 50% in the feces (Casida et al. 1962). The milk contained organosoluble 

radioactivity that was significantly above background within two hours of dosing. The excretion of 

radioactivity via various routes 24 hours following the administration of a single oral dose of 

[vinyl-14C] dichlorvos in human, rat, mouse, and hamster are listed in Table 2-5 (Hutson and Hoadley 

1972b). 

Several metabolism studies have shown the difficulty of determining the biological half-life of 

dichlorvos in animals. Orally administered dichlorvos undergoes rapid biotransformation, so that no 

intact dichlorvos could be detected in the blood or tissues of treated animals (Casida et al. 1962; 

Hutson and Hoadley 1972a, 1972b; Hutson et al. 1971; Potter et al. 1973a, 1973b). Intact dichlorvos 

has been detected in most tissues of the body only in rats and mice exposed by inhalation to the 

extremely high level of 90 mg dichlorvos/m3 (10 ppm) for 4 hours (Blair et al. 1975). The half-life of 

dichlorvos was 13.5 minutes in the kidney of rats exposed to 50 mg/m3

 for 2 or 4 hours. 

DICHLORVOS 74 

2. HEALTH EFFECTS 

Neither dichlorvos nor any of its metabolites are stored in the tissues of exposed animals (Wright et al. 

1979). Because small fractions of dichlorvos molecules, including carbon, phosphorus, and chlorine 

atoms, undergo reactions similar to natural components of the tissues, these dichlorvos-derived 

fractions are retained in the body for several days. 

2.3.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake 

and disposition of chemical substances to quantitatively describe the relationships among critical 

biological processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue 

dosimetry models. PBPK models are increasingly used in risk assessments, primarily to predict the 

concentration of potentially toxic moieties of a chemical that will be delivered to any given target 

tissue following various combinations of route, dose level, and test species (Clewell and Andersen 

1985). Physiologically based pharmacodynamic (PBPD) models use mathematical descriptions of the 

dose-response function to quantitatively describe the relationship between target tissue dose and toxic 

end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al. 

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and 

can be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low 

dose, from route to route, between species, and between subpopulations within a species. The 

biological basis of PBPK models results in more meaningful extrapolations than those generated with 

the more conventional use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan 

and Andersen 1994). In the early 1990s validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical 

substance-specific physicochemical parameters, and species-specific physiological and biological 

parameters. The numerical estimates of these model parameters are incorporated within a set of 
DICHLORVOS 75 

2. HEALTH EFFECTS 

differential and algebraic equations that describe the pharmacokinetic processes. Solving these 

differential and algebraic equations provides the predictions of tissue dose. Computers then provide 

process simulations based on these solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. 

The adequacy of the model is, therefore, of great importance, and model validation is essential to the 

use of PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 

1994). PBPK models provide a scientifically-sound means to predict the target tissue dose of 

chemicals in humans who are exposed to environmental levels (for example, levels that might occur at 

hazardous waste sites) based on the results of studies where doses were higher or were administered in 

different species. Figure 2-4 shows a conceptualized representation of a PBPK model. 

If PBPK models for dichlorvos exist, the overall results and individual models are discussed in this 

section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species 

extrapolations. 

No PBPK models are available for dichlorvos. 

2.4 MECHANISMS OF ACTION 

2.4.1 Pharmacokinetic Mechanisms 

The major characteristics of the pharmacokinetics of dichlorvos are its rapid absorption and rapid 

metabolism. This metabolism is so rapid in mammals that distribution is very difficult to study. 

Dichlorvos is a small (molecular weight = 221 daltons), lipophilic molecule and would be expected to 

be absorbed rapidly across cell membranes. Dichlorvos is absorbed by passive diffusion from the gut, 

lungs, and skin to the blood. Some dichlorvos can be inactivated by serum cholinesterase or 

DICHLORVOS 77 

2. HEALTH EFFECTS 

erythrocyte and neural acetylcholinesterase, but based on total esterase activity in the body, the liver 

is probably the major site of metabolism. Glutathione-dependent demethylation can also take place, but 

this appears to be important only in high-dose situations (Wright et al. 1979). The toxicity of a given 

dose of dichlorvos depends on how rapidly neural acetylcholinesterase is inhibited; if this occurs 

before metabolic processes can reduce the blood level of dichlorvos, significant toxicity will take 

place. 

Spontaneous reactivation of inhibited neural acetylcholinesterase has been studied in vivo (Pachecka 

et al. 1977; Reiner and Plestina 1979). After a single oral dose of 40 mg/kg dichlorvos in male rats 

(strain not stated), brain acetylcholinesterase was inhibited 47% after 5 minutes and 83% after 

15 minutes (Pachecka et al. 1977). Brain acetylcholinesterase was 60% inhibited at 2 hours, 36% 

inhibited at 12 hours, and near control levels at 48 hours. Following intravenous administration of 

dichlorvos in male rats (Reiner and Plestina 1979), the highest degree of inhibition after a dose of 

2.5 mg/kg was 85% at 30 minutes. Brain acetylcholinesterase inhibition returned to normal with a 

half-time of 2 hours. These relatively rapid times for reactivation indicate that recovery after a single 

dose is primarily by spontaneous reactivation. 

2.4.2 Mechanisms of Toxicity 

Dichlorvos exerts its toxicity by inhibiting neural acetylcholinesterase. The dichlorovinyloxy group 

of this molecule withdraws electrons from the phosphorus atom, leaving it susceptible to nucleophilic 

attack (Wright et al. 1979). One potential nucleophile is the serine hydroxyl group located at the 

active site of acetylcholinesterase. The products of this reaction are a dimethoxy-phosphorylated 

acetylcholinesterase molecule and dichloroacetaldehyde. The phosphorylated form of acetylcholinesterase is incapable of hydrolyzing acetylcholine. If this enzyme is inhibited, acetylcholine 

accumulates in the synapse and can interfere with neuron functioning.. The consequences of the 

disturbed cholinergic neurotransmission in the parasympathetic autonomic nervous system can include 

lacrimation, perspiration, miosis, nausea, vomiting, diarrhea, excessive bronchial secretions, 

bradycardia, increased salivation, and increased urinary frequency and incontinence. Effects on motor 

nerve fibers in the skeletal muscles can include muscle fasciculations, cramps, muscle weakness, and 

flaccidity. Effects on cholinergic synapses in the central nervous system result in drowsiness, fatigue, 

mental confusion, headache, convulsions and coma. 
DICHLORVOS 78 

2. HEALTH EFFECTS 

There is also evidence that repeated exposure to dichlorvos (5 mg/kg/day by intraperitoneal injection 

for 30 consecutive days) depletes both oxidized and reduced glutathione levels in rat brain (Julka et al. 

1992). Lowered glutathione levels may decrease the rate of detoxification of dichlorvos by the 

glutathione-dependent metabolic pathways. The full significance of depleted brain glutathione is not 

known for dichlorvos metabolism. 

The nervous system can accept a certain amount of acetylcholinesterase inhibition without overt 

toxic effects. In humans and animals, toxic signs are generally not seen until at least 20% of this 

enzyme (erythrocyte acetylcholinesterase used as a marker) has been inhibited (Ecobichon 1991). In 

an animal study, brain acetylcholinesterase after a 2-year inhalation exposure to dichlorvos was 

inhibited more than 90% compared to control animals (Blair et al. 1976), yet signs of cholinergic 

overstimulation were not observed. With dichlorvos and other organophosphate compounds, the best 

predictor of toxicity is not necessarily the actual percentage inhibition of acetylcholinesterase, but 

rather how rapidly this inhibition has occurred. Rapid inhibition does not give the nervous system time 

to adapt to acetylcholinesterase inhibition. This adaptation appears to involve desensitization and 

downregulation of muscarinic receptors (Fitzgerald and Costa 1993). 

2.4.3 Animal-to-Human Extrapolations 

Metabolic pathways for dichlorvos do not appear to be significantly different among animal species or 

between animal species and humans (Wright et al. 1979). Degradation by “A”-type esterases is the 

major pathway in all species examined. Metabolism also appears to be independent of both duration 

and route of exposure. Given the lack of information on what levels of dichlorvos exposure are 

necessary to produce toxicity in humans, selection of a suitable animal model for human toxicity is 

difficult. There do appear to be differences in sensitivity to dichlorvos among animal species. Orally 

exposed greyhound dogs (Snow and Watson 1973) and rabbits exposed by inhalation (Thorpe et al. 

1972) appear to be more susceptible to dichlorvos toxicity than mice or rats similarly exposed. 
DICHLORVOS 79 

2. HEALTH EFFECTS 

2.5 RELEVANCE TO PUBLIC HEALTH 

Overview 

Dichlorvos is an organophosphorus insecticide that has been in use in the United States and elsewhere 

since the early 1960s. Like other insecticides in this class, dichlorvos is not only extremely toxic to 

insects, but also can be toxic to humans if high enough doses are received. The toxicity of dichlorvos 

results from its inhibition of neural acetylcholinesterase. This enzyme is necessary to hydrolyze 

acetylcholine and terminate its action at synapses and neuromuscular junctions. The clinical signs of 

dichlorvos toxicity are the result of overstimulation of the parasympathetic autonomic nervous system, 

somatic nerve fibers, and cholinergic pathways in the brain. After acute exposure to high 

concentrations of dichlorvos by any route, signs such as lacrimation, perspiration, miosis, nausea, 

vomiting, diarrhea, bronchial secretion, dyspnea, increased salivation, and urinary frequency and 

incontinence can result from overstimulation of the parasympathetic autonomic nervous system. The 

actions of dichlorvos at neuromuscular junctions can result in muscle fasciculations (especially in fine 

facial muscles), cramps, muscle weakness, and paralysis. Dichlorvos can also act in the central 

nervous system to produce drowsiness, fatigue, mental confusion, headache, convulsions, coma, and 

depression of respiratory centers in the brain. 

There is limited information on the toxicity of dichlorvos to humans. The potential hazards of this 

chemical were well known before it came into use because of experience with other organophosphorus 

compounds. Exposure to levels of dichlorvos high enough to cause clinical symptoms of 

organophosphorus poisoning has been very rare in the United States. Limited studies of volunteers 

show that dichlorvos is rapidly metabolized by esterases in the liver and the blood; intact dichlorvos 

has never been detected in humans. Studies in laboratory animals show similar results. The metabolites 

of dichlorvos are polar compounds that are excreted into the urine; thus, no potential for 

bioaccumulation exists. Limited laboratory studies in animals have not shown adverse reproductive or 

developmental effects. However, sperm abnormalities occurred in rats treated with dichlorvos by 

intraperitoneal injection. 

Dichlorvos is mutagenic in a number of in vitro test systems. There is also evidence in studies on rats 

and mice that dichlorvos is carcinogenic in these species. Based on this evidence, the EPA has 

classified dichlorvos as a probable human carcinogen. There is no direct evidence that dichlorvos is 
DICHLORVOS 80 

2. HEALTH EFFECTS 

carcinogenic in humans; however. the animal data were used to predict exposure levels that would 

increase the risk of cancer in humans. The EPA has calculated that a lifetime of drinking water 

containing 0.1 μg/L would cause one extra case of cancer in one million people. 

Dichlorvos evaporates readily, so the most likely human route of exposure is by inhalation. This is 

most likely to occur during and/or after pesticide application. The U.S. Occupational Safety and 

Health Administration (OSHA) has set a Permissible Exposure Limit (PEL) of 1 mg/m3 (0.11 ppm) 

for dichlorvos in workplaces. Health effects could occur in workplaces if proper industrial hygiene 

and safety precautions are not followed. The exposure of the general population to dichlorvos is 

negligible. Dichlorvos has not been detected in drinking water in the United States and rarely in 

outdoor air (only at manufacturing sites). Monitoring of the food supply by the U.S. Food and Drug 

Administration (FDA) and other government agencies has very rarely detected dichlorvos. Thus, the 

risk of adverse health effects in the general population from dichlorvos exposure appears to be 

negligible. Dichlorvos is degraded by water and does not persist in the atmosphere or in bodies of 

water for more than a few days. 

For people living near hazardous waste sites, the potential for adverse health effects would depend on 

the amount of dichlorvos to which they were exposed. Dichlorvos has been detected in at least 3 of 

the 1,416 hazardous waste sites that have been proposed for inclusion on the EPA National Priority 

List (NPL) (HAZDAT 1995). However, the number of sites evaluated for dichlorvos is not known. 

The most likely routes of exposure for people living near hazardous waste sites would be by breathing 

dichlorvos-contaminated air, drinking dichlorvos-contaminated water, or skin contact with dichlorvoscontaminated soil. Monitoring of the air, drinking water, and soil levels of dichlorvos at these sites is 

necessary to predict the possibility of adverse health effects. 

Minimal Risk Levels for Dichlorvos 

Six minimal risk levels (MRLs) have been derived from the database compiled for this-profile; three 

for inhalation exposure (acute, intermediate, and chronic duration) and three for oral exposure (acute, 

intermediate, and chronic duration). In all cases, the toxic end point used for MRL derivation is 

inhibition of either erythrocyte or neural acetylcholinesterase activity. The neural form of this 

enzyme is the target for dichlorvos toxicity; the erythrocyte form is genetically identical (Taylor et al. 

1993) and can be used to approximate neural activity (Hayes 1982). There is no evidence for toxic 

effects 
DICHLORVOS 81 

2. HEALTH EFFECTS 

from dichlorvos exposure by any route or for any duration unless activity of either the erythrocyte or 

neural form of this enzyme is reduced by at least 20%. 

Inhalation MRL.s 

•	 An MRL of 0.002 ppm has been derived for acute-duration inhalation exposure (14 days or less) 

to dichlorvos. 

This MRL is based on a study in male Sprague-Dawley rats which were exposed continuously to 

atmospheres containing 8 different concentrations of dichlorvos ranging from 0.02 to 6.3 ppm over a 

3-day period (Schmidt et al. 1979). A NOAEL of 0.20 ppm was observed for inhibition of erythrocyte 

acetyl-cholinesterase. This NOAEL was adjusted by dividing by uncertainty factors of 10 for human 

variability and 10 for interspecies extrapolation. A clear dose-response relationship existed between 

exposure level and inhibition of erythrocyte acetylcholinesterase. 

Limited information on volunteers exposed to dichlorvos-containing atmospheres indicates that the 

0.002 ppm dichlorvos level should be protective for health effects in populations potentially exposed 

near hazardous waste sites. A group of volunteers exposed to 0.23 ppm dichlorvos (l00-fold higher 

than the MRL level) for 2 hours a day for 4 consecutive days had no inhibition of erythrocyte acetylcholinesterase 24 hours after the exposure or clinical signs of dichlorvos toxicity such as miosis 

(Witter et al. 1961). Miosis and significant depression of erythrocyte acetylcholinesterase activity 

(50%) were seen in this same study in rhesus monkeys exposed to 1.43 ppm (7 times higher than the 

humans). One volunteer exposed to 0.08 ppm dichlorvos for 20 hours also showed no clinical signs of 

dichlorvos toxicity (Blair et al. 1975). 

OSHA has established a PEL for dichlorvos of 0.1 ppm for a l0-hour workday. Practical use levels 

for insect control with dichlorvos are approximately 0.02 ppm. No human toxicity has been associated 

with this level of exposure (Hayes 1982). 

• An MRL of 0.0003 ppm has been derived for intermediate-duration inhalation exposure (14 days 

to one year) to dichlorvos. 

This MRL was derived from a NOAEL of 0.03 ppm dichlorvos for inhibition of brain acetylcholinesterase activity in a rat developmental study (Thorpe et al. 1972). The MFU was derived by 
DICHLORVOS 82 

2. HEALTH EFFECTS 

adjusting the NOAEL by a factor of 10 for animal to human extrapolation and another factor of 10 for 

human variability. 

Groups of 15 pregnant Carworth E rats were exposed to atmospheres containing 0, 0.25, 1.25. or 

6.25 mg/m3 (0, 0.03, 0.14, or 0.69 ppm) throughout their 20-day gestation period. Exposure of dams 

to all 3 concentrations of dichlorvos had no effect on developmental parameters (the number of fetal 

resorptions, late fetal deaths, litter size, or mean weight per fetus). Exposure at 0.03 ppm had no 

effect on erythrocyte or brain acetylcholinesterase. Exposure at 0.14 ppm resulted in a 29% inhibition 

of erythrocyte and a 28% inhibition of brain acetylcholinesterase, while exposure at 0.69 ppm 

resulted in 88% inhibition of erythrocyte acetylcholinesterase and an 83% inhibition of brain acetylcholinesterase. Brain and erythrocyte acetylcholinesterase activities were inhibited 83 and 88%, 

respectively, in dams in the high exposure (0.69 ppm) group. A NOAEL of 0.03 ppm was established 

for the neurological effect of brain acetylcholinesterase inhibition. A NOAEL of 0.03 ppm for brain 

acetylcholinesterase inhibition was also noted for rabbits exposed for a 28-day gestation period in 

this study (Thorpe et al. 1972). Significant maternal toxicity was observed in rabbits exposed to 0.69 

and 0.44 ppm dichlorvos, although this appears to have been related to mechanical failures that 

allowed higher concentrations of dichlorvos to enter the chambers for brief periods. However, no 

adverse developmental effects on the offspring were observed. 

No human studies were available for intermediate-duration inhalation exposure to dichlorvos. A 

NOAEL for developmental effects of 0.69 ppm was also observed in the MRL study (Thorpe et al. 

1972), but the NOAEL for neurological effects of 0.03 ppm was used to derive the MRL since the 

target of dichlorvos toxicity is, neural acetylcholinesterase. The database for intermediate-duration 

inhalation exposure to dichlorvos in animals is limited to the MRL study and a study in which pigs 

were exposed to dichlorvos at concentrations up to 0.015 ppm dichlorvos for 24 days (Loeffler et al. 

1976). A NOAEL of 0.015 ppm dichlorvos was identified for erythrocyte acetylcholinesterase 

inhibition. 

The intermediate-duration inhalation exposure MRL of 0.0003 ppm dichlorvos should be protective 

against health effects in populations potentially exposed at hazardous waste sites. This level is 

approximately l00-fold lower than that used in insect control (0.02 ppm), a level that has not resulted 

in human toxicity (Hayes 1982). 
DICHLORVOS 83 

2. HEALTH EFFECTS 

•	 An MRL of 0.00006 ppm has been derived for chronic-duration inhalation exposure (365 days or 

longer) to dichlorvos. 

This MRL is based on a 2-year inhalation study in Carworth E rats (Blair et al. 1976). A NOAEL of 

0.006 ppm in the male rats in this study was observed for inhibition of erythrocyte acetylcholinesterase. This NOAEL was adjusted by dividing by uncertainty factors of 10 for human variability 

and 10 for interspecies extrapolation. A dose-response relationship existed between exposure level and 

inhibition of erythrocyte acetylcholinesterase. 

Groups of 50 Carworth E strain rats of both sexes were exposed to atmospheres containing 0, 0.05, 0.5, 

or 5 mg dichlorvos/m3 (0, 0.006, 0.06, or 0.6 ppm) for 23 hours a day for 2 years as part of a 

carcinogenicity study (Blair et al. 1976). At the end of the study, the surviving rats were killed, blood 

was collected, and half the brain was used to determine brain acetylcholinesterase. Plasma cholinesterase and erythrocyte acetylcholinesterase were also measured. In males treated at 0.006 ppm, a 

NOAEL for brain and erythrocyte acetylcholinesterase was identified. Females at this dose had a 

12% reduction in erythrocyte acetylcholinesterase; this is also a NOAEL, since erythrocyte acetylcholinesterase inhibition of 20% or less is not considered an adverse effect. 

This is the only chronic inhalation study available for the derivation of an MRL. The EPA used this 

study to derive a reference concentration (RfC) of 0.0005 mg dichlorvos/m3

 (0.00006 ppm) for 

lifetime exposure to dichlorvos, the same value as derived for the MRL. The RfC “is an estimate 

(with uncertainty spanning perhaps an order of magnitude) of a daily inhalation exposure of the human 

population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious 

effects during a lifetime” (IRIS 1995). 

Oral MRLs 

•	 An MRL of 0.004 mg/kg/day has been derived for acute-duration oral exposure (14 days or less) 

to dichlorvos. 

This MRL is based on a study in male Sprague-Dawley rats that were treated for 14 days with 

dichlorvos by corn oil gavage (Teichert et al. 1976). A LOAEL of 4 mg/kg/day was identified on the 

basis of a 44% inhibition of brain acetylcholinesterase. The MRL was derived by dividing the 
DICHLORVOS 84 

2. HEALTH EFFECTS 

LOAEL value by 10 for use of a LOAEL (no NOAEL was identified in this study), by 10 for 

interspecies extrapolation, and by 10 for human variability. 

Male Sprague-Dawley rats were treated daily for 14 days with 4 mg/kg dichlorvos by gavage in corn 

oil (Teichert et al. 1976). Dichlorvos purity was 99%. Control animals received corn oil only. Ten 

animals were used in the control group and 11 in the treatment group. At the end of the 14-day 

dosing period, the rats were decapitated; the brains were removed, homogenized in 10 volumes of 

0.3% Triton X-100, and centrifuged for 10 minutes. Aliquots of the supematant were assayed for 

acetylcholinesterase activity by the hydrolysis of radioactive acetylcholine. Dichlorvos treatment at 

4 mg/kg/day over a 14-day period resulted in a 44% depression of brain acetylcholinesterase activity, 

which is considered a less serious LOAEL for neurological effects. In this same study, a single 

gavage dose of 40 mg/kg dichlorvos resulted in a 70% depression of brain acetylcholinesterase 1 

hour later, demonstrating, a dose-severity relationship. 

This is the only reliable study located for acute-duration oral exposure to dichlorvos where doses 

ranging from 5 to 10% of the LD50 were administered on a daily basis and brain acetylcholinesterase 

(one of the targets for dichlorvos) was measured rather than erythrocyte acetylcholinesterase. Most of 

the acute-duration oral studies for dichlorvos in rodent species were LD50 studies; representative LD50, 

values for the rat range from 56 to 97.5 mg/kg (Durham et al. 1957; Gajewski and Katkiewicz 1981; 

Ikeda et al. 1990). The 44% inhibition of brain acetylcholinesterase reported in this study is 

considered a less serious LOAEL; clinical signs were not reported in this study, but in another oral 

dosing study in Fischer 344 rats (NTP 1989) over an 11-day period, no clinical signs of dichlorvos 

neurotoxicity were reported in animals receiving up to 16 mg/kg/day dichlorvos. In a developmental 

study where CF-1 mice and New Zealand rabbits were orally exposed to dichlorvos during pregnancy 

(60 mg/kg/day over gestation days 6-l 5 in mice; 5 mg/kg/day over gestation days 6-l 8 in rabbits), no 

treatment-related effects were observed in the offspring. 

This MRL should be protective against health effects in individuals potentially exposed to dichlorvos 

at hazardous waste sites. Oral exposure at this level would not be expected to have any effect on 

neural acetylcholinesterase activity, the target for dichlorvos toxicity. The FAO/WHO Joint Meeting 

on Pesticide Residues has established an acceptable daily intake of dichlorvos for humans of 

0.004 mg/kg/day (FAO/WHO 1967). 
DICHLORVOS 85 

2. HEALTH EFFECTS 

• An MRL of 0.003 mg/kg/day has been derived for intermediate-duration oral exposure 

(15-364 days) to dichlorvos. 

This minimal risk level is based on a 21-day study in male volunteers who consumed 0.033 mg/kg/day 

in either a capsule form or in a 3-ounce container of gelatin at meals (Boyer et al. 1977). A NOAEL 

of 0.033 mg/kg/day was observed for inhibition of erythrocyte acetylcholinesterase. The MRL was 

derived by dividing the NOAEL by an uncertainty factor of 10 for human variability. 

Boyer et al. (1977) reported on a study designed to determine if different formulations would change 

the effect of dichlorvos on serum cholinesterase and erythrocyte acetylcholinesterase. Plasma cholinesterase and erythrocyte acetylcholinesterase were determined twice a week for 3 weeks in 30 male 

volunteers. The 24 men with the most stable enzyme activities were used in the study. Two treatment 

groups of 6 men each received 0.9 mg dichlorvos 3 times daily either in a pre-meal capsule filled with 

cottonseed oil or in a 3-ounce container of gelatin. Two other groups of 6 men each received placebo 

capsules or gelatin. The treated volunteers received 0.9 mg dichlorvos 3 times a day or 2.7 mg/day. 

The average weight of the volunteers was 81 kg, resulting in an average dose of 0.033 mg/kg/day. 

Dosing was started and carried out for a 21-day period during which plasma cholinesterase and 

erythrocyte acetylcholinesterase were measured twice a week by a pH titration method. Following 

the termination of dosing, plasma and erythrocyte activities were monitored twice weekly for 7 weeks. 

The observation of each individual’s cholinesterase activities was converted to a percentage of his 

pretrial average determinations. No clinical signs of neurotoxicity were noted in any of the subjects 

(tremor, pupillary response to light, and skin moisture were assessed). A NOAEL of 0.033 mg/kg/day 

dichlorvos was observed for inhibition of erythrocyte acetylcholinesterase. 

The reduction of serum cholinesterase observed in the study confirms that dichlorvos was absorbed by 

the volunteers under these conditions. No signs of clinical neurotoxicity were observed at any time in 

the volunteers. The dose given appeared to have been chosen for the express purpose of not causing 

erythrocyte acetylcholinesterase inhibition. This study was chosen for MRL derivation because it was 

the only one located that defined a NOAEL for humans for the end point of erythrocyte acetylcholinesterase inhibition. Several animal studies on intermediate-duration oral exposure to dichlorvos are 

available. NOAEL values for erythrocyte acetylcholinesterase inhibition were 3.5 mg/kg/day in 

Sherman rats exposed for 90 days by feed (Durham et al. 1957), 8 mg/kg/day in Fischer 344 rats 
DICHLORVOS 86 

2. HEALTH EFFECTS 

exposed by gavage for 32 days (NTP 1989) and 40 mg/kg/day in B6C3Fl mice exposed by gavage for 

33 days (NTP 1989). 

This MRL should be protective against health effects in individuals potentially exposed to dichlorvos 

at hazardous waste sites. Oral exposure at this level would not be expected to have any effect on 

neural acetylcholinesterase activity, the target for dichlorvos toxicity. The FAO/WHO Joint Meeting 

on Pesticide Residues has established an acceptable daily intake of dichlorvos for humans of 

0.004 mg/kg/day (FAO/WHO 1967). 

•	 An MRL risk level of 0.0005 mg/kg/day has been derived for chronic-duration oral exposure 

(364 days or more) to dichlorvos. 

This MRL level is based on a chronic feeding study in dogs (AVMAC Chemical Co. 1990; IRIS 

1995). Groups of Beagle dogs (4 per sex per dose, approximately 6-7 months old) were administered 

dichlorvos daily by gelatin capsule for 52 weeks at dose levels of 0, 0.1, 1.0, and 3.0 mg/kg/day. The 

0.1 mg/kg/day dose level was lowered to 0.05 mg/kg/day on day 22 due to inhibition of serum 

cholinesterase noted after 12 days on dichlorvos (the authors were attempting to assure a no-effect 

level for serum ChE). Observations included clinical signs, body weight, food consumption, 

ophthalmology, blood chemistry, necropsy, and histopathology. Serum cholinesterase and erythrocyte 

acetylcholinesterase were measured throughout the study. At termination of the study, the brain was 

weighed and brain acetylcholinesterase was measured. Histopathology was performed on the brain 

(with brainstem), cervical spinal cord, lumbar spinal cord, and the sciatic nerve. Serum cholinesterase 

and erythrocyte acetylcholinesterase were unchanged in the 0.05 mg/kg/day groups, and decreased in 

a dose-dependent manner at 1.0 and 3.0 mg/kg/day. Levels of inhibition did not increase over time of 

measurement (2-52 weeks). At termination of the study, brain acetylcholiesterase was unchanged at 

0.05 mg/kg/day. It was decreased 22% in males at 1.0 mg/kg/day, but not in females. At 

3.0 mg/kg/day, brain acetylcholinesterase was decreased 47% in males and 29% in females. No 

treatment-related changes were seen on histopathology for any of the tissues examined. 

The MRL was derived from the NOAEL level of 0.05 mg/kg/day for inhibition of brain acetylcholinesterase by adjusting by a factor of 10 for human variability and 10 for animal-to-human extrapolation. 
DICHLORVOS 87 

2. HEALTH EFFECTS 

The EPA has derived a reference dose (RfD) of 0.0005 mg/lcg/day based on a NOAEL for brain 

acetylcholinesterase inhibition of 0.05 mg/kg/day dichlorvos based on this study (IRIS 1995). 

Death. There have been several reports of deaths in humans as a result of exposure to dichlorvos 

(Hayes 1982). In one case, a woman who drank a pesticide containing dichlorvos died the following 

day, but the actual amount ingested was not determined. A 19-month-old girl died after eating a 

cakelike bait that contained dichlorvos. In this case, the amount of dichlorvos consumed was not 

determined. The bait also contained malathion, raising the possibility that an interaction may have 

occurred and contributed to the death. Two pesticide workers in Costa Rica were also reported to 

have died after spilling a dichlorvos-containing pesticide on their skin and failing to promptly wash it 

off (Hayes 1982). The concentration of dichlorvos in the pesticide was not reported, nor was the 

quantity spilled on the skin. 

Deaths have been reported in rats and rabbits after inhalation exposure to dichlorvos. In an early 

toxicity study (Durham et al. 1957), rats exposed to air saturated with dichlorvos died between 7 and 

62 hours after exposure began. Dichlorvos measured in the incoming air was 306 mg/m3 (34 ppm). 

The signs of poisoning preceding death included slow labored respiration, sialorrhea, and paleness of 

the extremities. Deaths were also reported among pregnant rabbits exposed by inhalation to dichlorvos 

for 28 days at 4 and 6.25 mg/m3 (0.44 and 0.69 ppm) (Thorpe et al. 1972). Before death, the animals 

were anorexic, lethargic, showed tremors, and had nasal discharges and diarrhea-all signs of 

dichlorvos neurotoxicity. Rats exposed to dichlorvos at levels up to 56 mg/m3 (6.2 ppm) for up to 

14 days survived (Schmidt et al. 1979) as did pregnant rats exposed by inhalation at levels up to 

6.25 mg/m3

 (0.69 ppm) (Thorpe et al. 1972). No studies on inhalation of dichlorvos in non-pregnant 

rabbits were located, so whether this greater sensitivity is a species difference or a consequence of 

pregnancy cannot be determined. Exposure of rats by inhalation for 2 years at 5 mg/m3

 (0.55 ppm) 

did not increase the death rate over controls in males or females (Blair et al. 1976). 

Deaths have been reported after single oral doses in a number of LD50 studies. LD50values in rats 

range from 56 mg/kg in female Sherman rats (Durham et al. 1957) to 97.5 mg/kg in male Fischer 344 

rats (Ikeda et al. 1990). In mice, LD50 values of 133 mg/kg for female CD-l mice and 139 mg/kg for 

males have been reported (Haley et al. 1975). In this study a reliable LD1 value of 84 mg/kg in male 

mice and 95 mg/kg in female mice was reported. Single acute oral doses of 150 mg/kg in male Swiss 

mice caused 100% lethality within 9 minutes (Mohammad et al. 1989). An oral LD50 of 157 mg/kg 
DICHLORVOS 88 

2. HEALTH EFFECTS 

has also been reported in crossbred pigs (Stanton et al. 1979). In intermediate-duration studies, all rats 

died after being orally exposed by feed at 180 mg/kg/day dichlorvos or more for 6 weeks (NCI 1977). 

All Fischer 344 rats exposed by gavage to dichlorvos at levels of 32 or 64 mg/dichlorvos died within 

13 weeks. as did 6 of 10 female rats exposed to 16 mg/kg/day dichlorvos (NTP 1989). Mice appear 

to be more resistant to dichlorvos toxicity in intermediate-duration studies. In a 6-week study where 

mice were orally exposed through feed, deaths were not reported until levels of 720 mg/kg/day were 

reached (NCI 1977). A 13-week gavage study in the same strain of mice reported deaths at 

80 mg/kg/day (NTP 1989). These studies suggest that dichlorvos is less toxic when consumed in feed 

than when administered by gavage, possibly due to slower absorption and the intermittent nature of 

exposure when consumed in feed. In a 2-year study on Fischer 344 rats and B6C3F1 mice, oral 

exposure to dichlorvos at doses of 4 and 8 mg/kg/day dichlorvos in rats, and 10, 20, and 40 mg/kg/day 

in mice had no effect on survival. Deaths have also been reported after dermal exposure in monkeys 

and rats (Durham et al. 1957; Gajewski and Katkiewicz 1981). Monkeys receiving daily doses of 

50 mg/kg/day dichlorvos and above died within 10 days; LD50, values of 70-107 mg/kg have been 

reported in rats. 

Parenteral doses causing death are considerably lower than those required by the inhalation, oral or 

dermal routes. An intravenous dose of 2.2 mg/kg undiluted dichlorvos was fatal in a greyhound dog 

(Snow and Watson 1973). The clinical signs of toxicity before death (hyperpnea, dyspnea, severe and 

progressive cyanosis) were the same as those seen in dogs that had been acutely poisoned orally. The 

importance of the liver in reducing dichlorvos toxicity was demonstrated in a study where rats were 

perfused with dichlorvos either through the femoral vein (dichlorvos entering the circulation directly) 

or the intestinal vein (dichlorvos passing through the liver before reaching the general circulation) 

(Gaines et al. 1966). Time to onset of symptoms was delayed about 3 times as long in rats infused 

through the intestinal vein compared to rats perfused through the femoral vein. All the rats perfused 

through the femoral vein died within 31 minutes (total dose 5 mg/kg), while none of the rats perfused 

through the intestinal vein died even though their total dose was 3 times as high (15.2 mg/kg). 

Systemic Effects. The systemic effects seen after dichlorvos exposure can generally be explained 

as the result of dichlorvos neurotoxicity. 

Respiratory Effects. Labored breathing has been reported in greyhound dogs (Snow and Watson 

1973) and monkeys (Durham et al. 1957) after acute oral exposure to high doses of dichlorvos. This 
DICHLORVOS 89 

2. HEALTH EFFECTS 

effect appears to be secondary to acetylcholinesterase inhibition in the respiratory tract. Increased 

cholinergic activity would be expected to cause increased bronchial secretions and bronchoconstriction 

and partial depolarization block at neuromuscular junctions could lead to labored breathing. 

Gastrointestinal Effects. Diarrhea, sometimes bloody, has been reported after acute oral exposure to 

dichlorvos in greyhound dogs (Snow and Watson 1973) and after intermediate-duration inhalation 

exposure in rabbits (Thorpe et al. 1972). Cholinergic stimulation in the gastrointestinal tract would be 

expected to cause increased intestinal motility and result in diarrhea. 

Dermal Effects. One case of contact dermatitis as a result of dichlorvos exposure was located. A 

52-year-old male truck driver who had been hauling pesticide containers presented with dermatitis of 

his neck, anterior chest, dorsal hands, and forearms (Mathias 1983). On the previous day, several 

containers spilled in his truck and he apparently had direct dermal contact with a pesticide containing 

5% dichlorvos, 15% petroleum distillates, and 80% trichloroethane. A faint papular dermatitis was 

present over the dorsal arms, hands, and V of the neck. Vertical erythematous, slightly scaling streaks 

were present over the lateral and posterior neck, a pattern suggesting that liquid droplets had produced 

the dermatitis. The dermatitis was treated with 1% hydrocortisone ointment. Follow-up examination 

6 weeks later demonstrated persistent vertical, mildly erythematous streaks over the posterior and 

lateral neck; the arms and anterior chest had cleared. Dermatitis resolved completely approximately 

10 weeks after onset. The persistence of dermatitis 2 months after exposure is very unusual, and the 

author speculated that this may be related to some unique local toxic effect of dichlorvos. 

Ocular Effects. Miosis was observed in monkeys after inhalation exposure to dichlorvos at 

12.9 mg/m3

 for 2 hours a day (Witter et al. 1961). This condition was no longer present the next 

morning. 

Body Weight Effects. Male Carworth E rats exposed to atmospheres containing 5 mg/m3 (0.6 ppm) 

for 2 years (Blair et al. 1976) were consistently 20% or more below the body weight ef control rats 

from the tenth week of treatment. However, no significant changes in body weight were noted in rats 

or mice of either sex after a 2-year oral exposure at doses ranging from 4 to 40 mg/kg for 5 days a 

week (NIT 1989). 
DICHLORVOS 90 

2. HEALTH EFFECTS 

Immunological and Lymphoreticular Effects. Twelve of 18 subjects in an occupational study 

of flower growers who had positive patch test reactions to triforine (1,4-bis [2,2,2-trichlorI-formamidoethyl] piperazine) also showed positive reactions to dichlorvos (Ueda et al. 1994). These 

subjects may have also been occupationally exposed to dichlorvos. 

Immunosuppression after oral exposure to dichlorvos in rabbits has been reported in two studies (Desi 

et al. 1978, 1980). A dose-related suppression of the humoral immune response induced by 

S. typhimurium was observed in rabbits administered 0.3-2.5 mgikg dichlorvos 5 days a week for 

6 weeks (Desi et al. 1978). A single oral dose of 120 mg/kg dichlorvos in male C57B1/6 mice that 

had been inoculated with sheep erythrocytes 2 days earlier suppressed the primary IgM response 

observed 48 hours later (Casale et al. 1983). Severe signs of dichlorvos neurotoxicity were noted and 

the authors stated that the immunosuppression observed in this study may have been mediated 

indirectly by toxic chemical stress. 

In a guinea pig maximization test conducted in this study, induction with dichlorvos by intradermal 

injection and topical application and subsequent challenge with topical dichlorvos solutions showed 

sensitization (Ueda et al. 1994). Cross-reactivity with dichlorvos was demonstrated in animals that had 

been induced with triforine. It is unknown if the immunosuppression seen with dichlorvos in animals 

is a direct effect or mediated by a cholinergic pathway. 

Neurological Effects. Dichlorvos exerts its toxic effects in humans and animals by inhibiting 

neural acetylcholinesterase. This enzyme is present at cholinergic synapses throughout the central 

and peripheral nervous systems and is responsible for hydrolyzing acetylcholine released from the 

presynaptic terminal. If this enzyme is inhibited, acetylcholine accumulates in the synapse, resulting in 

increased firing of the post-synaptic neuron or increased contractions in muscle. The consequences of 

this increased cholinergic activity in the parasympathetic autonomic nervous system can include 

lacrimation, perspiration, miosis, nausea, vomiting, diarrhea, excessive bronchial secretions, 

bradycardia, increased salivation, increased urinary frequency, and incontinence. Effects on motor 

nerve fibers in the skeletal muscles can include muscle fasciculations, cramps, muscle weakness, and 

paralysis. Effects on cholinergic synapses in the central nervous system result in drowsiness, fatigue, 

mental confusion, headache, convulsions, and coma. 
DICHLORVOS 91 

2. HEALTH EFFECTS 

This same enzyme is present in erythrocytes, where it is known as erythrocyte acetylcholinesterase. 

Both forms of acetylcholinesterase are produced by the same gene (Taylor et al. 1993). Erythrocyte 

and neural acetylcholinesterase are inhibited to roughly the same extent by exposure to dichlorvos 

and other organophosphorus compounds, and measurement of erythrocyte acetylcholinesterase is 

used as an indicator of the extent of inhibition of neural acetylcholinesterase (Hayes 1982). Another 

enzyme capable of hydrolyzing acetylcholine circulates in the blood and is called serum cholinesterase. 

The activity of this enzyme is inhibited by dichlorvos at lower levels of exposure than required for 

inhibition of erythrocyte acetylcholinesterase and is often used as a biomarker of exposure. 

Male volunteers exposed to atmospheres containing 0.25 or 0.7 mg/m3 showed no symptoms of 

neurological toxicity (Blair et al. 1975). One volunteer was exposed to 0.25 mg/m3

 for 10 hours, and 

another was exposed to 0.7 mg/m3 for 20 hours. 

Another group of seven male volunteers was exposed to dichlorvos-containing atmospheres in a 

simulated aircraft cabin to determine safe levels for aircraft insect control (Witter et al. 1961). In this 

study, the volunteers were exposed to dichlorvos on 4 consecutive days for either 1 or 2 hours. The 

average dichlorvos concentration in the first experiment was 0.49 mg/m3 (0.05 ppm); in a second 

experiment with the same group, it was 2.1 mg/m3

 (0.23 ppm). In the first experiment at 0.49 mg/m3, 

no changes were observed in serum cholinesterase or erythrocyte acetylcholinesterase in any of the 

men whether they had been exposed for 1 or 2 hours a day over the 4-day exposure period. There 

was a small inhibition of serum cholinesterase (about 20%) in 2 of 3 volunteers exposed for 2 hours a 

day for 4 consecutive days at 2.1 mg/m3. No changes were seen in erythrocyte acetylcholinesterase in 

any of the men exposed to 2.1 mg/m3

 for either 1 or 2 hours a day over the 4-day period. In this 

study, there was a 24-hour interval between exposure and the time blood was sampled for 

cholinesterase activities. 

In the same study, groups of 2 rhesus monkeys (one of each sex) were exposed to atmospheres 

containing 0.48, 2.3, 2.6, or 12.9 mg/m3

 (0.05, 0.25, 0.29, or 1.43 ppm) for 2 hours a day on 

4 consecutive days (Witter et al. 1961). Exposure for 2 hours a day on 4 consecutive days at 

0.48 mg/m3 had no effect on serum cholinesterase or erythrocyte acetylcholinesterase. Similar 

exposures at 2.3 and 2.6 mg/m3

, and the same sampling interval, had no effect on erythrocyte acetylcholinesterase but caused about a 20% inhibition of serum cholinesterase. Exposure at 12.9 mg/m3 

had significant toxic effects. The monkeys exposed at this level showed substantial inhibition of both 
DICHLORVOS 92 

2. HEALTH EFFECTS 

cholinesterases from the first day of exposure. Activity fell throughout the 4-day exposure period; 

serum cholinesterase was inhibited about 40-50% in both monkeys while erythrocyte acetylcholinesterase fell about 40% in one monkey and 67% in the other. Miosis was also noted in both monkeys 

at the end of each 2-hour exposure period. but was no longer present the following morning. 

Cholinesterase determinations after exposure was terminated indicated that 40-50 days were required 

for a return to pre-exposure levels. 

Rhesus monkeys housed in a chamber whose walls and ceiling had been sprayed with an emulsion of 

dichlorvos were observed for 2 weeks (Durham et al. 1957). The original concentration in the 

chamber was approximately 6 mg/m3 (0.66 ppm); it fell to about 1 mg/m3) (0.11 ppm) after 3 days and 

was about 0.1 mg/m3

 (0.01 ppm) for the remainder of the 2 weeks. No signs of neurological toxicity 

were observed. By the end of the first week, both serum cholinesterase and erythrocyte acetylcholinesterase had fallen from their pre-exposure levels. Inspection of a graph in this report indicates that 

levels of both blood cholinesterases fell about 50-60% during the first week of the study. Serum 

cholinesterase recovered partially in the second week, but erythrocyte acetylcholinesterase did not. 

After exposure was terminated, the activities of both enzymes were normal in about 5 weeks. 

Ten Sherman rats of each sex housed in the same chamber as the monkeys were also monitored in this 

experiment (Durham et al. 1957). No clinical signs of neurological toxicity were observed in the rats 

over the 2-week exposure period. There was a slight decrease in serum cholinesterase and erythrocyte 

acetylcholinesterase at the end of the first week (about 10% for each enzyme). At the end of 2 weeks, 

there was no difference between exposed rats and controls. Bronchial and erythrocyte acetylcholinesterase were measured in male Sprague-Dawley rats exposed to atmospheres ranging from 0 to 

56.64 mg/m3

 (0-6.3 ppm) over a 3-day period (Schmidt et al. 1979). A dose-dependent reduction in 

both bronchial and erythrocyte acetylcholinesterase was observed. Bronchial tissue acetylcholinesterase measured in homogenates from treated rats at 0.83 and 1.82 mg/m3

 (0.09 and 0.20 ppm) was 

lower than in control rats; 50% inhibition of bronchial tissue acetylcholinesterase took place at a dose 

(1.82 mg/m3

) that had no effect on erythrocyte acetylcholinesterase. Erythrocyte cholinesterase was 

inhibited more than 80% at 8.2 mg/m3 (0.91 ppm) after 3 days exposure. Clinical signs were not 

reported in this study, so the toxicological significance of this level of inhibition in the male SpragueDawley rats cannot be assessed. 
DICHLORVOS 93 

2. HEALTH EFFECTS 

Several studies in animals have addressed neurological end points after intermediate-duration 

inhalation exposure to dichlorvos. In a study of pregnant Carworth E rats exposed over their gestation 

period (20 days), dams exposed to atmospheres containing 6.25 mg/m3 (0.69 ppm) were less active 

than controls (Thorpe et al. 1972). Exposure at 0.25 mg/m3 (0.03 ppm) had no effect on erythrocyte or 

brain acetylcholinesterase. Exposure at 1.25 mg/m3 (0.14 ppm) resulted in a 30% inhibition of 

erythrocyte and brain acetylcholinesterase, while exposure at 6.25 mg/m3 resulted in 88% inhibition 

of erythrocyte acetylcholinesterase and an 83% inhibition of brain acetylcholinesterase. A similar 

experiment with pregnant Dutch rabbits over 28 days (Thorpe et al. 1972) showed inhibition of 14% 

and l0%, respectively, in erythrocyte and brain acetylcholinesterase at exposure of 0.25 mg/m3

. At 

exposures of 1.25 mg/m3

, erythrocyte acetylcholinesterase was inhibited 68% and brain acetylcholinesterase was inhibited 56% compared to controls. 

In a 2-year chronic inhalation study with dichlorvos (Blair et al. 1976), 50 Carworth E rats of each sex 

were exposed to atmospheres containing 0, 0.05, 0.5, or 5 mg/m3

 (0, 0.0055, 0.055, or 0.55 ppm). No 

clinical signs of neurological toxicity were seen in any of the groups, although 6 control rats and 

9 treated rats were reported as showing involuntary convulsive movements when being weighed. 

Acetylcholinesterase activity was measured in brain and erythrocytes, as was serum cholinesterase at 

the termination of this study. In male animals exposed to 0.05 mg/m3

, no significant differences with 

control animals were seen for any of the cholinesterases. Female animals at this dose had a 

statistically significant decrease of 12% in erythrocyte acetylcholinesterase. At 0.5 mg/m3, brain 

cholinesterase was 10% lower compared to controls in both male and female rats. Females at this 

dose also showed erythrocyte acetylcholinesterase inhibition of 31%, while the males were 

unaffected. At 5 mg/m3, brain acetylcholinesterase was inhibited by 79 and 81% in male and female 

rats, respectively. Erythrocyte acetylcholinesterase inhibition at this dose was 96% in the male rats 

and 95% in the female rats. 

Neurological effects have been seen in a number of studies in animals after acute oral exposure to 

dichlorvos. Male Fischer 344 rats exposed to dichlorvos by olive oil gavage during an LD50, study had 

signs of excessive cholinergic stimulation including salivation, tremors, lacrimation, fasciculations, 

irregular respiration, and prostration (Ikeda et al. 1990). In greyhound dogs receiving 11 or 22 mg/kg 

in a single dose, signs of neurological toxicity appeared within 7-15 minutes of dosing (Snow and 

Watson 1973). Restlessness was seen initially, followed by increased salivation, muscle fasciculations, 

involuntary urination, and repeated diarrhea, sometimes bloody. There was no apparent difference in 
DICHLORVOS 94 

2. HEALTH EFFECTS 

severity of clinical signs between dogs given 11 or 22 mg/kg. In dogs where erythrocyte acetylcholinesterase was determined (7 of 9), activity was decreased by at least 75%. One dog with 97% 

inhibition of erythrocyte acetylcholinesterase survived although suffering severe symptoms. 

Crossbred pigs receiving single doses from 18 to 560 mg/kg had clinical signs of neurological toxicity 

including hypoactivity, vomiting, ataxia, muscle fasciculations, uncoordinated movements, frothy 

salivation, and defecation (Stanton et al. 1979). 

In a 21-day study in volunteers given dichlorvos orally, no signs of neurological toxicity were seen at 

doses of 0.033 mg/kg/day. They were then given 0.9 mg dichlorvos 3 times a day for 21 days in 

either a pre-meal capsule or in a 3-ounce container of gelatin. Serum cholinesterase and erythrocyte 

acetylcholinesterase were measured twice a week during the exposure period. Once a week each 

volunteer had his vital signs measured and an examination made for tremor, pupillary response to 

light, and skin moisture. Following the termination of the study, serum cholinesterase and erythrocyte 

acetylcholinesterase were measured weekly for the next 7 weeks. No clinical signs of neurological 

toxicity were observed in any of the volunteers. Erythrocyte acetylcholinesterase was not inhibited at 

0.033 mg/kg/day in either the gelatin or capsule formulation. Serum cholinesterase was inhibited on 

average 38% in the group given the pre-meal capsule and 28% in the gelatin group. Measurements 

after the dosing period indicated that the half-life for regeneration of serum cholinesterase was 

13.7 days. 

In a 90-day study in female Sherman rats, groups of 10 animals were exposed to doses ranging from 

0 to 69.9 mg/kg/day in their feed. Two animals from each group were bled on days 3, 11, 60, and 90, 

and sernm cholinesterase and erythrocyte acetylcholinesterase were determined. No clinical signs of 

neurological toxicity were noted in any dosage group. Cholinesterase data were presented graphically 

so the percentage inhibition of the cholinesterases can only be estimated. For serum cholinesterase, 

doses of 0.4 and 1.5 mg/kg/day appeared to have no effect. Doses of 3.5 and 14.2 mg/kg/day 

appeared to have been inhibited by 25-40% of control by the third day of feeding, remained at this 

level up to 60 days, and rose to near control level by the termination of the experiment at 90 days. 

Serum cholinesterase in rats consuming 35.7 and 69.9 mg/kg/day fell by 50% after 3 days and 

remained at this level throughout the experiment. Erythrocyte acetylcholinesterase was unaffected at 

doses up to 3.5 mg/kg/day. Activity was inhibited by 30% after 3 days at 14.2 mg/kg/day and 

remained at this level until the end of the experiment. At 35.7 and 69.9 mg/kg/day, erythrocyte 
DICHLORVOS 95 

2. HEALTH EFFECTS 

acetylcholinesterase was inhibited by about 50% after 3 days and 80% after 10 days. There appeared 

to be some recovery to about 50% of control by the end of the experiment. 

Inhibition of erythrocyte and brain acetylcholinesterase, but not signs of neurotoxicity, were reported 

in Beagles receiving 0.05, 1.0, or 3 mg/kg/day dichlorvos in capsules for 52 weeks (AMVAC 

Chemical Corp. 1990; IRIS 1995). No changes were noted at 0.05 mg/kg/day, but erythrocyte acetylcholinesterase was inhibited 43-53% in dogs receiving 1 mg/kg/day and 81-87% in dogs receiving 

3 mg/kg/day. Brain acetylcholi-esterase was inhibited 22% in dogs receiving 1 mg/kg/day and 47% 

in dogs receiving 3 mg/kg/day. 

In a study where 3 cynomolgus monkeys were exposed to dichlorvos in xylene by daily dermal doses 

on a shaved area between the shoulder blades (Durham et al. 1957), cholinergic signs appeared within 

10-20 minutes of dosage. Signs of toxicity in general order of appearance were nervousness, 

incoordination, muscle fasciculations, excessive salivation, labored breathing, miosis, and inability to 

move. The authors stated that at any given dose, the cholinergic signs tended to become more severe 

with subsequent doses. Serum cholinesterase and erythrocyte acetylcholinesterase were measured in 

one of the monkeys which received 75 mg/kg/day. After 2 doses, erythrocyte acetylcholinesterase 

had declined by about 67%, while serum cholinesterase was unchanged. When these values were 

measured shortly after the next day’s dosage, the serum cholinesterase had fallen by about 33%, while 

erythrocyte acetylcholinesterase remained inhibited by about 67%. The serum cholinesterase 

recovered after 2 days without dosing, but the erythrocyte acetylcholinesterase did not. After 5 doses, 

the erythrocyte acetylcholinesterase had fallen by 90% and stayed there until death occurred after 12 

days, during which 10 doses were administered. 

Symptoms of neurological toxicity were also observed in Sherman rats dermally exposed to dichlorvos 

during an LD50, experiment (Durham et al. 1957). Rats which survived exhibited bulging eyes, 

excessive lacrimation, and generalized muscle fasciculation and tremors. Surviving rats appeared to be 

completely recovered after 24 hours. 

In a study involving daily dermal dosage in white Leghorn chickens, 3 hens receiving 

2.8-3.8 mg/kg/day exhibited a staggering gait after 14 days of treatment (Francis et al. 1985). Three 

hens receiving doses between 0.54 and 0.71 mg/kg/day showed no signs of neurotoxicity over 90 days 

of dosing. 
DICHLORVOS 96 

2. HEALTH EFFECTS 

Dichlorvos does not appear to cause organophosphate-induced delayed neurotoxicity (OPIDN. Certain 

organophosphate compounds can inhibit an enzyme called neuropathy target esterase (NIT), as well as 

neural acetylcholinesterase. Significant inhibition of NTE followed by irreversible binding to this 

enzyme (aging) results in a progressive, irreversible neuropathy in humans and experimental mammals 

and hens (Coppock et al. 1995; Johnson 1981). The in viva substrate for this enzyme is unknown, as 

is the biochemical mechanism underlying the subsequent development of neuropathy. In hens that had 

been pre-medicated with atropine to protect against the acute cholinergic effects of dichlorvos, 

subcutaneous injection of dichlorvos did not result in OPIDN (Durham et al. 19.56; Lotti and Johnson 

1978). Mild signs of ataxia were noted in atropine-pretreated hens 2 weeks after a single 

subcutaneous dose of 100 mg/kg dichlorvos (Caroldi and Lotti 1981). Subcutaneous administration of 

100 mg/kg dichlorvos to atropine pre-treated hens followed by the same dose within l-3 days 

produced ataxia in the hens (Johnson 1978). When dichlorvos was administered by a single 

intraperitoneal injection (5-60 mg/kg in hens and 5-30 mg/kg in rats), no significant pathological 

lesions of the OPIDN type were observed (Ehrich et al. 1995), or gait alterations characteristic of this 

neuropathy. 

Hens protected from the parasympathomimetic effects of dichlorvos by atropine developed clinical 

signs of ataxia (Francis et al. 1985; Johnson 1978). However, the apparent clinical signs of 

axonalpathy in the hens were not confirmed by histopathology. A number of different animal species 

have been experimentally intoxicated with dichlorvos. It has also been used as a systemic parasiticide 

in a number of domestic animal species (Hayes 1982). Humans have been intoxicated with 

dichlorvos and, because of medical intervention, recovered. In none of these studies and human 

poisoning incidents has OPIDN been reported. It is unlikely that dichlorvos OPIDN will occur in 

humans even in victims who have high levels of exposure and survive because of timely medical 

intervention. However, the interactions between dichlorvos and other pesticides for inducing OPIDN 

is not known. 

While signs of delayed neuropathy can be produced in animal models, this only occurs at doses far 

above the LD50. It is unlikely that dichlorvos would produce OPIDN in humans at doses that were 

not lethal because of acute cholinergic effects. 

Several effects on brain chemistry have been observed in studies where dichlorvos was administered 

intraperitoneally. Glutathione peroxidase activity was inhibited and the reduced and oxidized forms of 
DICHLORVOS 97 

2. HEALTH EFFECTS 

glutathione were depleted in female Wistar rats receiving 5 mg/kg/day (Julka et al. 1992). This 

suggests that glutathione-dependent metabolism of dichlorvos depletes glutathione levels and possibly 

leaves the brain vulnerable to oxidative damage. Dopamine, norepinephrine, and 5-hydroxy tryptamine 

levels were also reported depleted in the brain after 10 days of intraperitoneal administration at 

3 mg/kg/day in male rats (Ali et al. 1979). 

Reproductive Effects. No incident reports or epidemiological studies in humans on reproductive 

effects associated with dichlorvos exposure are available. In a reproductive toxicity study involving 

male CF-1 mice, groups of 16 mice were exposed to atmospheres containing 0, 30, or 55 mg/m3 (0, 

3.3, or 6.1 ppm, respectively) for 16 hours (Dean and Thorpe 1972). There were no differences 

between control and treated mice in the number of early fetal deaths, late fetal deaths, or live fetuses 

found in the pregnant females. The percentage of pregnancies for females mated to males exposed to 

30 and 55 mg/m3 (3.3 and 6.1 ppm) for 16 hours was similar to the controls (73-88%, mean 80.9%). 

Under these exposure conditions, dichlorvos does not appear to affect the fertility of male CF-1 mice. 

Sperm abnormalities were seen in C57BL/C3H mice injected intraperitoneally with 10 mg/kg/day for 

5 days (Wyrobek and Bruce 1975). About 6% of the sperm from dichlorvos-treated animals was 

abnormal compared to 1.8% of sperm from untreated animals. 

Developmental Effects. No studies in humans on developmental effects associated with 

dichlorvos exposure are available. Several animal studies examining developmental toxicity during 

continuous inhalation exposure to dichlorvos are available. Groups of 15 pregnant Carworth E rats 

were exposed to atmospheres containing 0, 0.25, 1.25, or 6.25 mg/m3 throughout their 20-day 

gestation period (Thorpe et al. 1972). At the end of 20 days, the rats were sacrificed and the uteri 

removed for examination. The number of live fetuses, stillbirths, and resorption sites were noted, and 

live fetuses were examined for external malformations. Exposure of dams to all three concentrations 

of dichlorvos had no effect on the number of fetal resorptions, late fetal deaths, litter size, or mean 

weight per fetus. One fetus in the litter of one dam in the 0.25 mg/m3

 group had skeletal defects and 

gastroschisis. No other fetuses from dams exposed to the same or higher concentrations had these 

defects, so the authors concluded that they were not exposure related. Brain and erythrocyte acetylcholinesterase activities were inhibited 83% and 88%, respectively, in dams in the high-dose 

(6.25 mg/m3

) group, suggesting that even very high levels of acetylcholinesterase inhibition are not 

associated with teratogenicity. 
DICHLORVOS 98 

2. HEALTH EFFECTS 

In a parallel experiment conducted on groups of 20 pregnant Dutch rabbits in this same study (Thorpe 

et al. 1972), similar results were seen. Dams exposed to 6.25 mg/m3 in the previous study had high 

mortality (16 of 20 died) so the doses used in this experiment were 0, 0.25, 1.25, 2, and 4 mg/m3 over 

the 28 day rabbit gestational period. Sizes of litters, fetal resorptions, and late fetal deaths were 

unaffected by inhalation exposure to dichlorvos. Mean weight per fetus was slightly depressed in 

dams exposed to 4 mg/m3, but the authors ascribed this to maternal toxicity. (Clinical signs were not 

reported, but 6 dams out of 20 in this group died during the study.) Three fetuses from groups that 

had not been exposed to dichlorvos had gastroschisis. Two dead fetuses from one litter in the 

4 mg/m3

 had cleft palates. 

No adverse developmental effects were observed in CF-1 mice treated by gavage with 60 mg/kg/day 

dichlorvos during gestation days 6-15 (Schwetz et al. 1979). There was no significant effect on 

implantations, mean number of fetuses per litter, incidence or distribution of resorptions, or on fetal 

body measurements. Similar results were observed in New Zealand rabbits treated by gavage with 

5 mg/kg/day over gestation days 6-18 (Schwetz et al. 1979). 

Genotoxic Effects. Dichlorvos is an electrophile and possesses a structural alert for methylating 

activity. Dichlorvos has been tested for genotoxicity in a number of in viva and in vitro systems. In 

general, dichlorvos was not genotoxic in in vivo studies (see Table 2-6) but was generally genotoxic or 

mutagenic in in vitro tests when metabolizing enzymes (S9 fraction) were not present (see Table 2-7). 

In the sex-linked lethal mutation test in Drosophila melunogaster, dichlorvos gave negative results 

when the flies were exposed by inhalation (Jayasuriya et al. 1973; Sobels and Todd 1979). Multiple 

generations of flies exposed to food containing dichlorvos for 18 months had increased mutations 

(Hanna and Dyer 1975). Salivary gland chromosome abnormalities were reported in larvae fed 1 ppm 

dichlorvos in food in one study (Gupta and Singh 1974), while another study at lower levels showed 

no effect (Kramers and Knaap 1978). 

No dominant lethal mutations were reported in ICR mice given a single intraperitoneal dose or 

consecutive daily doses of 5 or 10 mg/kg orally (Epstein et al. 1972). In a similar study where 

dichlorvos was administered by inhalation (30 or 55 mg/m3

 (3.3 or 6.1 ppm) to CF-1 mice, no 

dominant lethal mutations were observed (Dean and Thorpe 1972). 



DICHLORVOS 102 

2. HEALTH EFFECTS 

Male Q strain mice which received drinking water containing 2 mg/L dichlorvos for 7 weeks did not 

show chromosome damage in bone marrow cells, spermatogonia, or primary spermatocytes 

(Moutschen-Dahmen et al. 1981). In a micronucleus test, Swiss mice given daily intraperitoneal 

injections of dichlorvos (0.0075 or 0.015 mg/kg) for 2 days showed no aberrations in structure or 

number of chromosomes in bone marrow cells. CF-1 mice exposed to 64-72 mg/m3 for 16 hours or 

to 5 mg/m3 for 21 days did not show chromosome abnormalities (Dean and Thorpe 1972). In Syrian 

hamsters, however, intraperitoneal injections at 3, 6, 15, and 30 mg/kg did cause increases in the 

number of cells with aberrant chromosomes (Dzwonkowska and Hubner 1986). 

Dichlorvos was positive for binding to calf thymus DNA in vitro (Lofroth 1970; Segerbeck 1981). 

Dichlorvos was negative for DNA binding in viva in rats (Wooder et al. 1977) and in mice (Segerbeck 

1981). 

In mutagenicity tests with S. typhimurium tester strains, dichlorvos has generally been positive without 

metabolic activation and negative in the presence of S9. Dichlorvos in the presence of metabolic 

activation was negative in strains TA 98 (Braun et al. 1982), TA 1535 (Braun et al. 1982; Carere et al. 

1976; Moriya et al. 1978) and TA 1536, 1537, and 1538 (Braun et al. 1982; Carere et al. 1976). 

Without metabolic activation, dichlorvos was positive in strain TA 100 (Moriya et al. 1978), strain 

1530 (Hanna and Dyer 1975), strain 1535 (Carere et al. 1978; Hanna and Dyer 1975; Moriya et al. 

1978; Shirasu et al. 1976), but negative in strains 1536, 1537, and 1538 (Moriya et al. 1983; Shirasu 

et al. 1976). 

The lack of dichlorvos genotoxicity in in vivo studies is most likely due to the fact that while 

dichlorvos possesses methylating activity, the phosphorous atom of the molecule is a stronger 

electrophile than the methyl carbon atoms (Wright et al. 1979). In tissues and blood, dichlorvos is 

much more likely to react with “A”-type esterases, serum cholinesterase, or acetylcholinesterase than 

with DNA (WHO 1989). 

Cancer. In a 2-year carcinogenicity study of inhalation exposure to dichlorvos, groups of 

50 Carworth rats of each sex were exposed at levels of 0, 0.05, 0.5, or 5 mg/m3

 (Blair et al. 1976). 

Only 11 of the unexposed male controls and 25 of the unexposed female controls survived to the end 

of the study. Survival was actually highest in the rats receiving the highest dose of dichlorvos (32 of 

50 males and 34 of 50 females). Microscopic examination revealed a wide range of lesions in all 
DICHLORVOS 103 

2. HEALTH EFFECTS 

groups; the authors stated that these are commonly seen in old rats of this strain. There was a high 

incidence in all groups of chronic nephrosis, focal myocardial fibrosis, degenerative artery disease, 

lymphoid hyperplasia of the spleen. and testicular atrophy. Common tumors in all groups were 

adenomas of the anterior pituitary gland, parafollicular cell adenomas, and carcinomas of the thyroid 

gland, adrenal pheochromocytomas, and mammary fibroadenomas in the females. Examination of the 

lungs (presumably the tissue receiving the highest dose) revealed minor changes in all groups. 

Peribronchial and perivascular lymphoid aggregates, mild degrees of bronchiolitis and focal alveolar 

thickening were noted. Electron microscopic examination of bronchi, bronchioli, and alveoli of a 

small number of control and high-dose group animals showed no differences between the groups. 

None of the lesions in the study was associated with dichlorvos exposure. 

The high mortality of the control animals in this study makes interpretation of the carcinogenicity data 

problematic. The possibility also exists that exposure by the oral and dermal routes may have 

occurred. However, no significant increase in neoplastic or non-neoplastic lesions was found in the 

nasal and respiratory tract tissues that received the highest dose of dichlorvos. 

In a carcinogenicity study in Osborne-Mendel rats, groups of 50 animals of each sex were originally 

dosed through feed at levels of 45 and 90 mg/kg/day (NCI 1977). During the initial 3 weeks of 

dosage, acute signs of toxicity were observed including tremor and diarrhea in the 90 mg/kg/day 

group. For this reason, the dosages were then lowered to 30% of the original. The TWA doses over 

the go-week period of dosing were 13.5 and 29.3 mg/kg/day. After the go-week dosing period, the 

animals were observed for a further 30 weeks until sacrifice. Adverse clinical signs (hematuria, rough 

coats, epistaxis) were noted in control and dosed animals, gradually increasing during the second year 

of the study. The authors stated that at the end of the study the rats were in generally poor condition. 

The matched control groups had significantly lower survival than the treated groups at the end of the 

study, mainly due to deaths during the 30-week observation period after treatment. At the termination 

of the study, only 2 of 10 male rats and 5 of 10 female rats survived in the matched control groups. 

For this reason, these control rats were pooled with control rats from concurrent studies for 

comparison with the treated groups. Of the male rats, 76% of the high-dose and 64% of the low-dose 

group survived to the end of the study as did 84% of the high-dose and 80% of the low-dose females. 

Numerous inflammatory, degenerative, and proliferative lesions commonly seen in aged rats occurred 

with approximately equal frequency in the treated and the pooled control rats. Several non-neoplastic 
DICHLORVOS 104 

2. HEALTH EFFECTS 

lesions occurred more frequently in the treated rats than in the controls. These included aggregates of 

alveolar macrophages in the lungs, interstitial fibrosis of the myocardium, and focal follicular cell 

hyperplasia of the thyroid gland in the male rats. Benign endocrine neoplasms occurred frequently in 

both test and control rats. There was a high incidence of benign mammary neoplasms in both control 

and treated rats. Because of the low survival of the matched control rats, control animals from other 

concurrent studies were pooled for statistical analysis. The authors stated that on the basis of 

variability of both the incidence and type of spontaneous lesions and the lack of significant proportions 

of tumors in the dosed groups compared to the controls, no statistical significance could be attached to 

the incidence of the tumors seen in the dichlorvos-treated rats in this study. Because of the poor 

survival of control animals in this study, the results are difficult to interpret. 

In another carcinogenicity study in rats, groups of 50 Fischer 344 rats of each sex were dosed with 

dichlorvos by oral gavage in corn oil at levels of 0, 4, or 8 mg for 5 days a week for 103 weeks (NTP 

1989). No significant differences in survival were noted between any groups. Survival rates were: 

31 of 50 for male and female controls, 25 of 50 males and 26 of 50 females in the low-dose group, 

and 24 of 50 males and 26 of 50 females in the high-dose group. 

Statistically significant increases in neoplasms were observed in the pancreas and hematopoietic 

system in male rats and in the mammary gland in female rats. Adenoma of the exocrine pancreas 

exhibited a significant positive trend and the incidences were greater in treated than control groups (15 

of 50 in vehicle control, 23 of 49 in the low-dose group and 30 of 50 in the high-dose group). When 

horizontal sections of the pancreas were examined, additional adenomas were observed. When the 

data from both methods were combined, the incidences of pancreatic adenoma were 25 of 50 in the 

controls, 30 of 50 in the low-dose, and 33 of 50 in the high-dose group. The incidence for the treated 

groups was statistically significant compared to the vehicle controls. 

A significant positive trend for mononuclear cell leukemia was also observed in the male rats. This 

neoplasm was found in 11 of 50 controls, 20 of 50 in the low-dose group, and 21 of 50 in the high-dose 

group. A significant positive trend also occurred for mammary gland tumors in female rats. 

Fibroadenoma, adenoma, or carcinoma occurred in 11 of 50 control rats, 20 of 50 in the low-dose 

group, and 17 of 50 in the high-dose group. Peer review panels characterized these results as “some 

evidence” of carcinogenic activity in male rats and “equivocal evidence” in female rats. The control 
DICHLORVOS 105 

2. HEALTH EFFECTS 

animals in these studies had substantially higher incidences of neoplasms at these sites than the 

historical incidence compiled from other studies. 

Dichlorvos was also tested for carcinogenicity in male and female B6C3F1 mice by a similar 2-year 

protocol (NTP 1989). Because of higher toxicity in male mice during the dose-finding study, groups 

of 50 male mice were dosed by corn oil gavage at 0, 10, or 20 mg/kg for 5 days a week, and the 

females dosed at 0, 20, or 40 mg/kg for 5 days a week. 

The only neoplasm that occurred with a significant positive trend in treated compared to control mice 

was squamous cell papilloma and carcinoma of the forestomach. The overall incidence of this lesion 

in male mice was 1 of 50 in the controls, 1 of 50 in the low-dose group, and 5 of 50 in the high-dose 

group. In the females, overall incidences were 5 of 49 in the control group, 6 of 49 in the low-dose 

group and 18 of 50 in the high-dose group. Incidence in male controls was near the historical 

incidence of l%, but was higher in the female controls (10% compared to 1%). Peer review panels 

characterized the level of carcinogenic activity as “some evidence” in male mice and “clear evidence” 

in female mice. 

The mechanism of dichlorvos-induced carcinogenicity is not known. A study of B6C3F1 mouse 

forestomach from mice treated with dichlorvos by gavage in corn oil (Benford et al. 1994) showed 

increases in replicative DNA synthesis (associated with increased cell proliferation). Unscheduled 

DNA synthesis (associated with DNA repair) was not increased by dichlorvos treatment, but was 

increased by 1 -methyl-3-nitro-1 -nitrosoguanidine, a known genotoxic forestomach carcinogen. The 

authors concluded that the forestomach tumors seen in the 2-year carcinogenicity study (NTP 1989) 

may have been mediated by enforced cellular proliferation rather than by a genotoxic mechanism. 

Two organizations have reviewed the evidence for dichlorvos carcinogenicity in humans from the 

results obtained in test systems. The EPA has classified dichlorvos as a probable human carcinogen 

(Category B2) on the basis of significant increases of forestomach tumors in mice and-leukemias and 

pancreatic acinar adenomas in rats. Supporting evidence included observation of tumors at other sites 

in the rat and the observation that dichlorvos and a major metabolite, dichloroacetaldehyde, are 

mutagenic in in vitro test systems. A structurally related compound, dichloropropene, also causes 

forestomach tumors in rodents (IRIS 1995). The International Agency for Research on Cancer (IARC) 

has classified dichlorvos as possibly carcinogenic to humans (Group 2B) based on inadequate evidence 
DICHLORVOS 106 

2. HEALTH EFFECTS 

in humans for the carcinogenicity of dichlorvos and sufficient evidence in experimental animals for the 

carcinogenicity of dichlorvos (IARC 1991). 

2.6 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They 

have been classified as markers of exposure, markers of effect, and markers of susceptibility 

(NAS/NRC 1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of 

biomarkers as tools of exposure in the general population is very limited. A biomarker of exposure is 

a xenobiotic substance or its metabolite(s), or the product of an interaction between a xenobiotic agent 

and some target molecule(s) or cell(s) that is measured within a compartment of an organism (NRC 

1989). The preferred biomarkers of exposure are generally the substance itself or substance-specific 

metabolites in readily obtainable body fluid(s) or excreta. However, several factors can confound the 

use and interpretation of biomarkers of exposure. The body burden of a substance may be the result 

of exposures from more than one source. The substance being measured may be a metabolite of 

another xenobiotic substance (e.g., high urinary levels of phenol can result from exposure to several 

different aromatic compounds). Depending on the properties of the substance (e.g., biologic half-life) 

and environmental conditions (e.g., duration and route of exposure), the substance and all of its 

metabolites may have left the body by the time samples can be taken. It may be difficult to identify 

individuals exposed to hazardous substances that are commonly found in body tissues and fluids (e.g., 

essential mineral nutrients such as copper, zinc, and selenium). Biomarkers of exposure to dichlorvos 

are discussed in Section 2.6.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within 

an organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAWNRC 1989). This definition encompasses biochemical or cellular signals 

of tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital 

epithelial cells), as well as physiologic signs of dysfunction such as increased blood pressure or 

decreased lung capacity. Note that these markers are not often substance specific. They also may not 

be directly adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of 

effects caused by dichlorvos are discussed in Section 2.6.2. 
DICHLORVOS 107 

2. HEALTH EFFECTS 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism’s 

ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be an 

intrinsic genetic or other characteristic or a preexisting disease that results in an increase in absorbed 

dose, a decrease in the biologically effective dose, or a target tissue response. If biomarkers of 

susceptibility exist, they are discussed in Section 2.8, Populations That Are Unusually Susceptible. 

2.6.1 Biomarkers Used to Identify or Quantify Exposure to Dichlorvos 

Dichlorvos at high doses will cause classical symptoms of organophosphate toxicity, such as miosis, 

tremor, increased salivation, lacrimation, pulmonary secretions, and perspiration. If these symptoms 

occur together and the individual has recently been in contact with pesticides containing dichlorvos, it 

is highly likely that exposure to dichlorvos has occurred. Exposure to toxic concentrations of 

dichlorvos or other organophosphates can be confirmed by blood tests. Dichlorvos can reduce the 

activity of two enzymes in the blood, serum cholinesterase and erythrocyte acetylcholinesterase. 

Serum cholinesterase appears to be more sensitive to inhibition by dichlorvos and other 

organophosphates than erythrocyte acetylcholinesterase. However, serum cholinesterase activity 

recovers more rapidly than erythrocyte acetylcholinesterase because of the higher turnover rate of 

serum proteins compared to erythrocytes. Exposures that occurred two weeks or more before testing 

probably would not be reflected in an inhibition of serum cholinesterase. Because of the human 

variability in activity of these enzymes, follow-up determinations showing a rise back to a constant 

activity are more reliable evidence that an exposure has taken place than a single determination. 

Confirmation that specific exposure to dichlorvos has taken place is difficult and requires sophisticated 

analytical chemistry. Intact dichlorvos has not been detected in humans and only rarely in animals. 

This is because of the rapid metabolism of dichlorvos by esterases in the liver and blood (see 

Section 2.3). The major metabolic products of dichlorvos are dimethyl phosphate and the glucuronide 

conjugate of dichloroethanol. These compounds are rapidly excreted into the urine and will have left 

the body within a day or two of cessation of exposure. Dimethyl phosphate has been measured in the 

urine of pesticide applicators by extraction with an ion exchange resin, derivitization, and gas 

chromatography (Das et al. 1983). Dichloroethanol has been detected in the urine of a human 

volunteer after glucuronidase treatment and gas-liquid chromatography (Hutson and Hoadley 1972b). 

However, because of interference by endogenous urine components, the measurement had a relatively 

high error. Exposure to naled and trichlorphon, two organophosphates that are converted in the body 
DICHLORVOS 108 

2. HEALTH EFFECTS 

to dichlorvos, would also have to be ruled out before a definitive determination of dichlorvos exposure 

could be made (Hayes 1982). 

2.6.2 Biomarkers Used to Characterize Effects Caused by Dichlorvos 

The toxic effects of dichlorvos are caused by its inhibition of neural acetylcholinesterase in the 

peripheral and central nervous systems. This inhibition is reflected by the level of depression of 

erythrocyte acetylcholinesterase activity in the blood. 

The nervous system can accept a certain amount of acetylcholinesterase inhibition without overt 

toxic effects. In humans and animals, toxic signs are generally not seen until at least 20% of this 

enzyme (measured as erythrocyte acetylcholinesterase) has been inhibited (Ecobichon 1991). In an 

animal study, brain acetylcholinesterase after a 2-year inhalation exposure to dichlorvos was 

inhibited more than 90% compared to control animals (Blair et al. 1976), yet no symptoms of 

cholinergic overstimulation were observed. With dichlorvos and other organophosphate compounds, 

the best predictor of toxicity is not necessarily the actual percent inhibition of acetylcholinesterase, 

but rather how rapidly this inhibition has occurred. Rapid inhibition does not give the nervous system 

time to physiologically adapt to acetylcholinesterase inhibition. This adaptation appears to involve 

desensitization and down-regulation of muscarinic receptors (Fitzgerald and Costa 1993). 

For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC 

Subcommittee Report on Biological Indicators of Organ Damage (1990) and for information on 

biomarkers for neurological effects see OTA (1990). 

2.7 INTERACTIONS WITH OTHER CHEMICALS 

The major interaction of dichlorvos with other chemicals would be with chemicals that have the same 

mechanism of action (i.e., organophosphate and carbamate pesticides). Simultaneous exposure to 

dichlorvos and one of these chemicals could possibly have an additive effect on inhibition of neural 

acetylcholinesterase. There has been one case of serious human toxicity caused by ingestion of a bait 

cake that contained both dichlorvos and malathion (Hayes 1982). Chemicals which can react with the 

serine residue at the active site of the “A”-type esterases (e.g., diisopropylfluorophosphate [DEP]) 

could also increase the toxicity of dichlorvos by interfering with metabolism. 
DICHLORVOS 109 

2. HEALTH EFFECTS 

2.8 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to dichlorvos than will most 

persons exposed to the same level of dichlorvos in the environment. Reasons may include genetic 

makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., cigarette 

smoke). These parameters may result in reduced detoxification or excretion of dichlorvos, or 

compromised function of target organs affected by dichlorvos. Populations who are at greater risk due 

to their unusually high exposure to dichlorvos are discussed in Section 5.6, Populations With 

Potentially High Exposure. 

People with impaired “A”-type esterase function would be unusually susceptible to dichlorvos 

exposure , because of an impaired ability to metabolize dichlorvos absorbed by the body. This 

population would primarily be composed of people suffering from liver diseases. Pregnant women 

have lower levels of serum cholinesterase and are more susceptible to agents such as succinylcholine 

which is metabolized by this enzyme. Dichlorvos can bind stoichiometrically to this enzyme and 

inhibit its activity, so pregnant women are at least hypothetically more susceptible to dichlorvos 

exposure than other populations. A similar effect could be expected in individuals with inherited 

abnormally low serum cholinesterase levels. 

2.9 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects 

of exposure to dichlorvos. However, because some of the treatments discussed may be experimental 

and unproven, this section should not be used as a guide for treatment of exposures to dichlorvos. 

When specific exposures have occurred, poison control centers and medical toxicologists should be 

consulted for medical advice. The following texts provide specific information about treatment 

following exposures to dichlorvos: 

“Cholinesterase inhibitor pesticides” in Handbook of Poisonilzg, 1987, Appleton and Lange, 

Norwalk, CT; R.H. Dreisbach and W.O. Robertson. pp 11 l-l 18. 

“Organophosphates and other insecticides” in Clinical Management of Poisoning and Drug 

Overdose, 2nd. edition, 1990, W.B. Saunders, Philadelphia; L.M. Haddad and J.F. 

Winchester, eds. pp 10761087. 
DICHLORVOS 110 

2. HEALTH EFFECTS 

“Insecticides: organophosphates and carbamates” in Goldfrank’s Toxicologic Emergencies, 5th 

edition, 1994, Norwalk, CT; L.R. Goldfrank, N.E. Flomenbaum, N.A. Lewis, R.S. Weisman, 

M.A. Howland, and R. S. Hoffman. pp 1105-l 119. 

2.9.1 Reducing Peak Absorption Following Exposure 

If exposure has occurred by the oral route, gastric lavage would reduce peak absorption following 

exposure. Dichlorvos generally does not absorb to other materials. so treatment with activated 

charcoal, for example would probably be ineffective. If exposure has occurred by the dermal route, 

rinsing the exposed skin with large amounts of flowing water and soap would greatly reduce exposure. 

2.9.2 Reducing Body Burden 

Because dichlorvos does not accumulate in the body and is rapidly metabolized to less toxic 

metabolites which are rapidly excreted into the urine, specific efforts to reduce the body burden would 

not appear to be necessary. 

2.9.3 Interfering with the Mechanism of Action for Toxic Effects 

Dichlorvos has the same mechanism of action as other organophosphorus insecticides. Poisonings 

with these types of chemicals are common enough that specific and effective medical interventions 

have been developed. The life-threatening effects of dichlorvos poisoning are related to its effects on 

the respiratory system (respiratory depression, bronchospasm, increased bronchial secretions, 

pulmonary edema. muscular weakness). If these symptoms are present, artificial respiration and 

suctioning are performed via an endotracheal tube. Atropine is used to counteract the muscarinic 

effects of dichlorvos with care being taken that symptoms of atropine overdose do not occur (dry 

mouth, dilatation of the pupils). The inhibited neural acetylcholinesterase can be reactivated by 

intravenous administration of specific antidotes such as pralidoxime. 

2.10 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with 

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of dichlorvos is available. Where adequate information is 

not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to 
DICHLORVOS 111 

2. HEALTH EFFECTS 

assure the initiation of a program of research designed to determine the health effects (and techniques 

for developing methods to determine such health effects) of dichlorvos. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will 

be evaluated and prioritized, and a substance-specific research agenda will be proposed. 

2.10.1 Existing information on Health Effects of Dichlorvos 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

dichlorvos are summarized in Figure 2-5. The purpose of this figure is to illustrate the existing 

information concerning the health effects of dichlorvos. Each dot in the figure indicates that one or 

more studies provide information associated with that particular effect. The dot does not necessarily 

imply anything about the quality of the study or studies, nor should missing information in this figure 

be interpreted as a “data need.” A data need, as defined in ATSDR’s Decision Guide for Identifying 

Substance-Specific Data Needs Related to Toxicological Profiles (ATSDR 1989), is substance-specific 

information necessary to conduct comprehensive public health assessments. Generally, ATSDR 

defines a data gap more broadly as any substance-specific information missing from the scientific 

literature. 

As shown in Figure 2-5, information is available for humans on death after oral and dermal exposure, 

and on systemic and neurological effects after inhalation and oral exposure. This information is 

generally for acute-duration exposure only, except for one 21-day study of oral exposure in volunteers 

that examined the neurological end point of erythrocyte acetylcholinesterase inhibition. 

Nonneurological end points generally have not been observed in humans, except those that result 

secondarily from the neurological toxicity of dichlorvos. 

Animal data exist for death by inhalation, oral, and dermal routes for acute durations, and inhalation 

and oral routes for intermediate and chronic durations. Data also exist for systemic effects that are 

secondary to the neurotoxicity of dichlorvos. Limited immunological data are available only for the 

oral route for the acute and intermediate duration. Data are available for neurological effects for all 

DICHLORVOS 113 

2. HEALTH EFFECTS 

routes and all durations except dermal intermediate and chronic. Reproductive and developmental 

studies are available for the inhalation and oral route. Genotoxic and cancer studies are available for 

the inhalation and oral route. 

2.10.2 Identification of Data Needs 

Acute-Duration Exposure. Populations in the vicinity of hazardous waste sites may be exposed 

to dichlorvos for brief periods. Exposure would most likely occur by the inhalation route, but dermal 

exposure by contact with contaminated soil is also possible. Cases of accidental and intentional 

poisonings in humans (Hayes 1982) indicate that the central and peripheral nervous systems are the 

major target organs for dichlorvos toxicity by the oral and dermal routes. It can be inferred from 

animal studies that this is true for inhalation exposure as well (Durham et al. 1957). The specific 

target of dichlorvos is the enzyme which catalyzes the hydrolysis of the neurotransmitter acetylcholine, 

neural acetylcholinesterase. Minimal risk levels (MRLs) have been derived for the acute duration for 

both the inhalation route (0.002 ppm) (Schmidt et al. 1979) and the oral route (0.004 mg/kg/day) 

(Teichert et al. 1976) based on inhibition of erythrocyte acetylcholinesterase and neural acetylcholinesterase activity. The study used for the acute-duration oral MRL (Teichert et al. 1976) did not 

include a dose at which no adverse effects occurred (NOAEL); an acute-duration oral study in animals 

which included doses of dichlorvos that produced both a NOAEL and a LOAEL would be valuable. 

Little information on acute-duration dermal exposure is available except for lethality studies. Since 

this is a possible route of exposure from contaminated soil at hazardous waste sites, studies which 

establish a threshold value for acetylcholinesterase inhibition in a sensitive species would be useful. 

Intermediate-Duration Exposure. A well-conducted study is available for human 

intermediateduration oral exposure to dichlorvos (Boyer et al. 1977). This study was used to derive an 

oral MRL of 0.003 mg/kg/day dichlorvos based on a NOAEL of 0.033 mg/kg/day for erythrocyte 

acetyl-cholinesterase inhibition. An intermediate-duration inhalation study in rats (Thorpe et al. 1972) 

was used to derive an inhalation MRL of 0.0003 ppm dichlorvos based on a NOAEL of 0.03 ppm for 

brain acetylcholinesterase inhibition. Results in animal studies indicate that the toxic effects of 

intermediate-duration exposure dichlorvos are similar to those for the acute duration. Several studies 

have identified immunosuppression in rats treated orally with dichlorvos over the intermediate duration 

(Desi et al. 1978, 1980). This effect may be secondary to central cholinergic stimulation; further 

studies are needed to clarify this point. No studies on intermediate-duration dermal exposure to 
DICHLORVOS 114 

2. HEALTH EFFECTS 

dichlorvos were located: studies on this topic would be helpful to establish threshold values of acetylcholinesterase inhibition. 

Chronic-Duration Exposure and Cancer. Chronic-duration exposure is the most likely type of 

exposure that would be experienced by people living near hazardous waste sites. Because of the 

physical properties of dichlorvos, this exposure is most likely to be by the inhalation route. The only 

chronic-duration study by the inhalation route was done on rats in 1976 (Blair et al. 1976). A 

chronicduration inhalation MRL of 0.00006 ppm was derived, based on brain acetylcholinesterase 

inhibition in this study. While this study found no evidence of an increased incidence of cancer in 

these rats, it does not meet present-day standards for carcinogenicity studies of this type. A chronicduration oral study has been done in rats and mice, and produced evidence of carcinogenicity by this 

route (NTP 1989). Since inhalation is the most likely route of exposure in humans for dichlorvos, a 

chronic duration inhalation study in rats and mice could help public health assessment of potential risks 

of dichlorvos. 

Genotoxicity. Dichlorvos has been tested in virtually every available genotoxicity test. In bacteria, 

dichlorvos bound covalently to DNA and caused DNA damage and point mutations. Dichlorvos 

induced gene conversion, mutation and aneuploidy in yeast and fungi. In D. melunogasrer, 

chromosomal but not sex-linked recessive lethal mutations were produced. In mammalian cells 

in vitro, dichlorvos caused DNA strand breaks, mutation, sister chromatid exchange, chromosomal 

aberrations and cell transformation. The effects on in vitro systems were in general greatly reduced 

when metabolic activation was present. Dichlorvos was negative for genotoxicity in in vivo tests for 

the induction of unscheduled DNA synthesis, sister chromatid exchange, micronucleus formation, 

chromosomal aberrations, or dominant lethal mutation by the inhalation route. The database for 

dichlorvos genotoxicity is extensive and no data needs have been identified. 

Reproductive Toxicity. No information on reproductive toxicity in humans after dichlorvos 

exposure is available. Dichlorvos did not cause reproductive toxicity by the inhalation route over the 

acute duration in male mice (Dean and Thorpe 1972). No gross or histological evidence of 

treatmentrelated damage to reproductive tissues (prostate, testes, epididymis, ovaries or uterus) was 

seen in rats (4 or 8 mg/kg/day) or mice (10, 20, or 40 mg/kg/day) orally exposed to dichlorvos by 

gavage for 2 years (NTP 1989). No reproductive studies on dichlorvos by the oral or dermal routes are 

available; 
DICHLORVOS 115 

2. HEALTH EFFECTS 

animal reproductive toxicity studies by these routes would be useful. No multi-generational 

reproductive studies on dichlorvos are available. 

Developmental Toxicity. No information on developmental toxicity in humans after dichlorvos 

exposure is available. Dichlorvos did not cause developmental toxicity in rats exposed throughout 

pregnancy by the inhalation route to up to 0.69 ppm or up to 0.44 ppm in rabbits (Thorpe et al. 1972). 

Similar results were obtained with mice and rabbits exposed to 0.44 ppm dichlorvos for 7 hours a day 

during the organogenesis period of gestation (Schwetz et al. 1979). Developmental toxicity was not 

observed in mice exposed orally by gavage to 60 mg/kg/day dichlorvos over gestation days 6-15, or in 

rabbits exposed similarly to 5 mg/kg/day dichlorvos over gestation days 6-18 (Schwetz et al. 1979). 

The database for dichlorvos developmental toxicity is adequate, except that a multi-generation 

developmental study in rabbits would be useful. 

Immunotoxicity. No information was located on immunotoxicity in humans after dichlorvos 

exposure. Only a few studies were located that addressed immunotoxicity in animals after dichlorvos 

exposure. Immunosuppression after oral exposure to dichlorvos in rabbits has been reported in three 

studies (Casale et al. 1983; Desi et al. 1978, 1980). A dose-related suppression of the humoral 

immune response induced by S. typhimurium was observed in rabbits (Desi et al. 1978). A single oral 

dose of 120 mg/kg dichlorvos in male C57B l/6 mice that had been inoculated with sheep erythrocytes 

2 days earlier suppressed the primary IgM response observed 48 hours later (Casale et al. 1983). 

Severe signs of dichlorvos neurotoxicity were noted, and the authors stated that the immunosuppression observed in this study may have been mediated indirectly by toxic chemical stress. It is 

unknown if the immune suppression noted after dichlorvos exposure in these studies is secondary to 

cholinergic stimulation. Immunotoxicity studies employing atropine prophylaxis to counteract the 

anticholinesterase effect of dichlorvos are necessary to resolve this question. Additional studies 

examining potential longer-term effects of dichlorvos on the immune system by all three routes as well 

as short-term effects by the inhalation and dermal routes would be important for estimating human 

susceptibility for populations exposed for varying lengths of time at hazardous waste sites. 

Neurotoxicity. A few case reports in humans indicate that the central and peripheral nervous 

systems are the targets of dichlorvos toxicity after oral and dermal exposure (Hayes 1982). Numerous 

animal studies by the inhalation, oral and dermal routes corroborate these findings (Durham et al. 

1957; Snow and Watson 1973; Stanton et al. 1979) and have identified the molecular target for 
DICHLORVOS 116 

2. HEALTH EFFECTS 

dichlorvos neurotoxicity, neural acetylcholinesterase. The database for neurotoxicity was sufficient to 

derive MRLs for acute-, intermediate-, and chronic-duration inhalation exposure and for acute- and 

intermediate-duration oral exposure based on observation of NOAELs and one less serious LOAEL for 

inhibition of neural and/or erythrocyte acetylcholinesterase. Further studies are needed to elucidate 

the mechanism of adaptation to dichlorvos neurotoxicity. In longer term experiments (Blair et al. 

1976), levels of inhibition that would cause serious toxicity if caused by an acute dose (up to 90% for 

neural acetylcholinesterase) are tolerated without clinical signs of dichlorvos neurotoxicity. Studies 

that determine a threshold dose for dichlorvos neurotoxicity by the dermal route are also needed since 

this is a potential route for exposure to populations near hazardous waste sites. 

The adverse neurological effects of dichlorvos can be explained largely by its inhibition of neural 

acetylcholinesterase, but the possibility exists that other potential targets in the nervous system exist. 

For example, there is evidence that chlorpyrifos oxon (the active metabolite of the organophosporus 

insecticide chlorpyrifos) can inhibit muscarinic receptor binding in vitro. This inhibition occurs at 

concentrations lower than those necessary to inhibit neural acetylcholinesterase (Huff et al. 1994). 

In vitro receptor binding in brain membrane preparations or in cultured cells would determine if 

dichlorvos has a similar effect on muscarinic receptor function. Little is known about the potential for 

interaction between dichlorvos and other neurotoxic agents; further studies on this topic would be 

useful. 

Epidemiological and Human Dosimetry Studies. At the present time, very few people are 

exposed to dichlorvos outside occupational groups. The major group potentially exposed, pest control 

workers, generally use several different pesticides, and it would be virtually impossible to identify a 

group exposed primarily to dichlorvos. The lack of adequate analytical methods that would 

specifically quantify dichlorvos exposure (as opposed to other organophosphorus or carbamate 

pesticides) precludes human dosimetry studies. Thus, no data needs for epidemiological or human 

dosimetry studies were identified. 

Biomarkers of Exposure and Effect. 

Exposure. Reliable biomarkers for exposure to dichlorvos already exist (serum cholinesterase, 

erythrocyte acetylcholinesterase, and clinical symptoms of neurotoxicity). However, reliable methods 
DICHLORVOS 117 

2. HEALTH EFFECTS 

to distinguish dichlorvos intoxication from that caused by other organophosphorus compounds do not 

exist. 

Effect. Reliable biomarkers for the effect of dichlorvos exist (cholinergic symptoms of neurotoxicity 

and erythrocyte acetylcholinesterase). There is no evidence that toxic effects occur in humans at 

levels of dichlorvos that do not significantly inhibit erythrocyte acetylcholinesterase. 

Absorption, Distribution, Metabolism, and Excretion. Very little information is available on 

the toxicokinetics of dichlorvos in humans. Dichlorvos appears to be rapidly absorbed by all routes of 

exposure. This rapid rate of absorption is inferred from the time to onset of clinical signs and/or 

cholinesterase inhibition because of the difficulty in assaying dichlorvos in biological tissues. This is 

due to the rapid hydrolysis of dichlorvos by tissue esterases, particularly in the liver and the serum. 

The half-life of dichlorvos in human blood in vitro is about 10 minutes (Blair et al. 1975). 

Distribution is also inferred from cholinesterase inhibition, but there does not appear to be any 

preferential distribution to particular tissues. Dichlorvos does not appear to be stored or concentrated 

in any tissue (Casida et al. 1962). The major metabolites of the esterase-catalyzed degradation of 

dichlorvos are dimethyl phosphate and dichloroacetaldehyde (Wright et al. 1979). Dimethyl phosphate 

is excreted in the urine, while dichloroacetaldehyde can be reduced to dichlorethanol or dehalogenated 

to glyoxal, which enters 2-carbon metabolism (Hutson et al. 1971). Dichloroethanol is either 

conjugated to glucuronic acid and excreted or dehalogenated and further metabolized. There is also 

some evidence that dichlorvos can be demethylated in a glutathione-dependent process (Blair et al. 

1975). 

Further characterization of the esterases involved in dichlorvos degradation is necessary to determine if 

any possibility exists that human polymorphism may make some groups more susceptible to 

dichlorvos toxicity than others. Since inhalation exposure is the most likely route of exposure at 

hazardous waste sites, determination of the blood-gas partition coefficient for dichlorvos in human 

blood is needed to more accurately quantify the potential health risks for a given atmospheric level of 

dichlorvos. 

Comparative Toxicokinetics. Differences in sensitivity to dichlorvos toxicity appear to exist in 

mammalian test animal species. Generally, for a given dose, rabbits are the most sensitive, followed 

in order by dogs, rats, and mice (NTP 1989; Snow and Watson 1973; Thorpe et al. 1972). The 

comparative toxicokinetic parameters that might explain these differences are unknown. Further 
DICHLORVOS 118 

2. HEALTH EFFECTS 

studies via all three exposure routes in test species would be useful in determining similarities and 

differences between humans and animals and the effects of pregnancy on dichlorvos metabolism. 

Methods for Reducing Toxic Effects. Further studies on retarding gastrointestinal absorption of 

dichlorvos would be useful in the treatment of poisoning. No methods exist for reducing the body 

burden of dichlorvos. The medical management of the toxic effects of dichlorvos (respiratory support, 

atropine treatment, reactivation of neural acetylcholinesterase with oximes) is similar to that for 

poisoning by other organophosphorus pesticides. Any improvements in the management of 

organophosphorus poisoning would apply to dichlorvos. 

2.10.3 Ongoing Studies 

M. Cunningham of the National Institute of Environmental Health Sciences, Research Triangle Park, 

North Carolina, is conducting feeding studies in mice with dichlorvos and several other chemicals to 

investigate the relationship between cell proliferation and carcinogenesis. 
DICHLORVOS 119 

3. CHEMICAL AND PHYSICAL INFORMATION
 

3.1 CHEMICAL IDENTITY
 

Information regarding the chemical identity of dichlorvos is located in Table 3- 1.
 

3.2 PHYSICAL AND CHEMICAL PROPERTIES
 

Information regarding the physical and chemical properties of dichlorvos is located in Table 3-2.
 



DICHLORVOS 123 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL
 

4.1 PRODUCTION 

Initially synthesized in the late 1940s, dichlorvos was not registered for insecticidal use in the United 

States under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) until 1948 (EPA 1987b). 

Until large scale production of dichlorvos began in the late 1950s, the compound was chiefly 

encountered as an impurity in the pesticide trichlorfon (IARC 1979). One method of production is the 

dehydrochlorination of trichlorfon in aqueous alkali at 40-50◦

C (WHO 1989). Dichlorvos is also 

produced commercially by a reaction of trimethyl phosphite and chloral (Cremlyn 1978; Sittig 1980; 

WHO 1989). 

As a pesticide, dichlorvos is commonly referred to as DDVP, which is an abbreviation for 

2,2-dichlorovinyl dimethyl phosphate (Farm Chemical Handbook 1984). Commercially available 

formulations include aerosols and soluble concentrates. Historically, product formulations have also 

included dusts, granules, emulsifiable concentrates, wettable powders, flea collars, baits, and 

impregnated resin strips, and pellets/tablets (EPA 1990b; Farm Chemical Handbook 1984; IARC 1991; 

PIP-Dichlorvos 1993; The Agrochemicals Handbook 1991). Dichlorvos is also formulated in 

combination with a variety of other pesticides including dimethoate, dinocap, fenchlorphos, 

fenitrothion, iodofenphos, lindane, malathion, methoxychlor, phosalone, piperonyl, pirimiphos-methyl, 

propoxpur, tetrasul, pyrethrins, and trichlorfon (IARC 1991; The Agrochemicals Handbook 1991). By 

September 1987, the EPA had issued 885 end-use registrations for dichlorvos products. Of this total, 

94 products were formulation intermediates, 24 were special local need registrations, 13 were technical 

products, and 49 were intrastate products (EPA 1987b). 

In the past, basic producers of dichlorvos in the United States have included: Denka Chemia B.V., 

E.I. du Pont de Nemours and Company, Fermenta Animal Health, Kenco Chemical and Manufacturing 

Corporation, McLaughlin Cormley King Company, Prentiss Drug and Chemical Company, and SDS 

Biotech Corporation (EPA 1987b). Currently, only one manufacturer, AMVAC Chemical Corporation 

in Los Angeles, California, can be clearly documented as producing technical grade dichlorvos in the 

United States (Farm Chemical Handbook 1994; SRI 1994). 
DICHLORVOS 124 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Information on historic production volumes of dichlorvos in the United States is limited. Production 

volumes based on estimates of annual use of dichlorvos in the United States for the years 1971, 1976, 

and 1980, suggest production levels as high as 4.6 million pounds (2.1 million kg) per year (IARC 

1991; WHO 1989). In 1984, estimated production of dichlorvos in the United States was 500,000 kg 

(1.1 million pounds) (IARC 1991). In 1985, the estimated production of dichlorvos (active ingredient) 

in the United States was 2 million pounds (0.9 million kg) (EPA 1988a). Estimates of annual use of 

dichlorvos (active ingredient) in the United States during 1989 were less than 450,000 kg 

(992,000 pounds) and this use level was significantly lower than the total use in previous years (IARC 

1991). It is unlikely, therefore, that production volumes for dichlorvos in the United States increased 

significantly between 1985 and 1989. Information on more recent production volumes was not found; 

however, it is likely that production volumes have decreased since the late 1980s due to changes in 

use patterns and registration cancellations (see Section 4.3). 

Table 4-l lists the facilities in each state that manufacture or process dichlorvos, the intended use, and 

the range of maximum amounts of dichlorvos that are stored on site. The data listed in Table 4-l are 

derived from the Toxics Release Inventory (TR193 1995). Only certain types of facilities were 

required to report (EPA 1995a). Therefore, this is not an exhaustive list. 

4.2 IMPORT/EXPORT 

Official government statistics on imports and exports for chemicals such as dichlorvos are summarized 

under broad generic categories such as “pesticides” or “organophosphates.” No quantitative data on 

current or historic import volumes of dichlorvos were located in the available literature. With respect 

to exports, FIFRA generally prohibits the EPA from releasing complete information on pesticide 

production, sales, and distribution. No governmental agency maintains current records concerning 

what specific pesticides are exported. No quantitative data on current or historic export volumes of 

dichlorvos were located in the available literature. 

4.3 USE 

Dichlorvos has been used widely as an insecticide and miticide since 1961 to control internal and 

external parasites in livestock and domestic animals, to control insects in houses, and for crop 

protection (IARC 1991). It is an organophosphorus insecticide with fumigant and penetrant action that 

DICHLORVOS 126 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

exhibits anticholinesterase effects (EPA 1987b, 1990a; Worthing 1983). Dichlorvos is poisonous if 

swallowed, inhaled, or absorbed through the skin; therefore, it acts as a contact and stomach poison 

(WHO 1985). Because dichlorvos is one of the more volatile pesticides in this class of compounds, it 

has been used primarily for its fumigant action (Cremlyn 1978). It is effective in controlling nuisance 

pests (e.g., caterpillars, flies, mosquitoes, and cockroaches) in and around domestic dwellings, stored 

products, commercial transportation vehicles, and livestock buildings. In 1974, dichlorvos was ranked 

as one of three active ingredients most frequently used by pest control operators. The aerosol 

formulation of dichlorvos was viewed as the most popular (EPA 1976). In 1975, it was estimated that 

approximately 80% of the dichlorvos produced in the United States was formulated into 

polyvinylchloride resin strips containing 20% by weight of dichlorvos (EPA 1976; IARC 1979, 1991). 

Prior to marketing this formulation for controlling flies and mosquitoes in the home in 1967, resin 

strips were introduced to the dairy and poultry industries (IARC 1991). According to the National 

Household Pesticide Usage Study of 1976 and 1977, the most frequently observed pesticide in a 

sample of 8,254 households was dichlorvos (EPA 1987b). Other uses have included direct application 

to packaged nonperishable processed or bulk-stored raw agricultural commodities (EPA 1990b, 

1993b). Dichlorvos also has therapeutic uses; it has been incorporated in animal feed as an 

antihelminthic to treat a variety of internal and external parasites in swine, horses, and dogs (Farm 

Chemical Handbook 1984; HSDB 1996; PIP-Dichlorvos 1993). 

Until the early 1970s, dichlorvos or mixtures containing dichlorvos were routinely used by fisheries 

biologists for the control of nuisance species such as carp (Marking 1992). Dichlorvos also has been 

added directly to water to control parasites in intensive fish farming (WHO 1989). Concern over 

problems associated with toxic and environmentally persistent organochlorine and organophosphate 

pesticide agents has led to restrictions on the use of such agents in natural lakes or other waterbodies, 

but dichlorvos has continued to be used in aquaculture to control various types of fish parasites. The 

use of such methods is very common in some European countries; for example, in Norway it is used 

in the aquaculture production of Atlantic salmon and rainbow trout (Cusack and Johnson 1990; Hoey 

et al. 1991; Horsberg and Hoey 1990; McHenery et al. 1991). Information on the current use of 

dichlorvos in aquaculture in the United States was not found. 

In 1971, a total of 1,116,000 kg (2.44 million pounds) of dichlorvos were used in agricultural 

applications with 16,000 kg (35,000 pounds) being used on crops and 1.1 million kg (2.4 million 

pounds) being used on livestock and livestock buildings (IARC 1979). In 1980, the total usage of 
DICHLORVOS 127 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

dichlorvos (active ingredient) in the United States was estimated to range from 1.58 to 2.1 million kg 

(3.5-4.6 million pounds) (EPA 1980 as cited in IARC 1991). This includes 0.68-1.2 million kg 

(1.5-2.6 million pounds) for agricultural uses, 450,000 kg (1 million pounds) for public health 

applications, and about 450,000 kg (1 million pounds) for household use. With respect to agricultural 

uses of dichlorvos during 1980, approximately 340,000 kg (748,000 pounds) were used on dairy cattle, 

30,000 kg (66,000 pounds) on beef cattle, 6,000 kg (13,200 pounds) on hogs, 2,000 kg (4,400 pounds) 

on poultry, 14,000 kg (30,800 pounds) on other livestock, and 50,000 kg (110,000 pounds) for 

treatment of tobacco. The estimated annual agricultural use of dichlorvos on crops in the United 

States during 1982 was 112,500 kg (248,000 pounds) of active ingredient (Gianessi 1986). From the 

mid- to late-1980s, agricultural applications represented 60% of the total annual usage in the United 

States: 35% was used on beef and dairy cattle, swine, and livestock buildings; and 25% was used on 

sheep, poultry, other livestock, tobacco, and greenhouse-grown food crops including lettuce, 

mushrooms, and tomatoes. Commercial, institutional, and industrial uses accounted for 25% of the 

annual usage; and domestic uses, including household pesticides and pet collars, accounted for 15% of 

the usage. The annual usage of dichlorvos (active ingredient) for 1989 was estimated to be less than 

450,000 kg (990,000 pounds) (IARC 1991). This use level was significantly lower than the total use 

in previous years (IARC 1991). No information on more current use levels was identified in the 

available literature. 

Drastic changes in use patterns (EPA 1993a) and restrictions on or cancellations of some registrations 

(EPA 1991a) are likely to have resulted in decreasing production of dichlorvos. For example, there 

has been a decline in the use of dichlorvos in unique agricultural applications such as ornamental 

perennials (EPA 1993a), and its use on figs was canceled in October 1989 (EPA 1991a). As a result 

of scientific investigations initially begun in the early 1980s and determination that exposure to 

dichlorvos from the registered uses may pose a carcinogenic risk, the EPA announced in February 

1988 that it was initiating a Special Review for products containing dichlorvos (EPA 1991a). 

Dichlorvos has since been classified as a probable human carcinogen based on effects observed in 

mice and rats. The EPA has required cautionary warning labels on products containing dichlorvos; 

and the FDA has required warnings for pest strip products to discourage their use around kitchens, 

restaurants, or other areas where food is prepared. Recently, the EPA issued a “stay” on the effective 

date for the revocation of the food additive regulation for residues of dichlorvos in or on certain 

packaged processed foods (EPA 1993b, 1994a). 
DICHLORVOS 128 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

As of September 28, 1995, the EPA proposed cancellation of most uses of the pesticide dichlorvos and 

proposed restrictions on retained uses (TOXLIST 1995). The proposed uses to be cancelled included 

all home uses such as hanging pest strips, room foggers, and pet flea collars. EPA also proposed that 

most retained uses be restricted to specially trained certified applicators. Because of dietary cancer 

risk, the EPA also proposed cancelling uses of dichlorvos on non-perishable raw and processed 

agricultural commodities which are stored in bulk, packages, or bags. The following uses are being 

proposed for cancellation because of unacceptable risks to persons applying dichlorvos or persons who 

live or work in areas where the chemical is applied: all warehouses, including tobacco warehouses; 

commercial, institutional, and industrial areas including food service, food manufacturing and food 

processing facilities; dichlorvos applied by hand to farm livestock (except poultry); all home uses 

(including uses by residents and commercial applicators); uses on ornamental lawns, turf and plants; 

and in airplanes. The EPA proposes to retain the following uses: mushroom houses and greenhouses 

(only automatic foggers or fogging through a port), kennels, feedlots, insect traps, garbage dumps, 

direct application to poultry, automated application to livestock, animal premises, manure, and in 

passenger buses. The uses in mushroom houses, greenhouses, and passenger buses will also be 

cancelled unless specified re-entry period statements (no re-entry within 48 hours after application 

except in emergency) are added to the product labels. Because of the uncertainty associated with 

continuing the registration of a number of registered uses, it is difficult to predict future production or 

use patterns for the United States. 

4.4 DISPOSAL 

Dichlorvos was designated as a hazardous substance under the Federal Resource Conservation and 

Recovery Act, and the clean-up of discharges of dichlorvos to the environment are further regulated by 

the Clean Water Act (CWA) Amendments of 1977 and 1987 and the Comprehensive Environmental 

Response, Compensation, and Liability Act (CERCLA). Regulations and advisories governing the 

treatment and disposal of dichlorvos-containing waste are detailed in Section 7. Generally, the 

recommended disposal methods for dichlorvos include alkaline hydrolysis, landfilling,and incineration. 

Prior to disposal, the product from the alkali treatment is mixed with soil that is rich in organic matter. 

Another possible disposal technology is to combine residues of dichlorvos with sawdust followed by 

incineration at high temperature in a unit equipped with effluent gas scrubbers (IRPTC 1985). 
DICHLORVOS 129 

4. PRODUCTION, IMPORT/EXPORT. USE, AND DISPOSAL 

No historic or current information was located on the volume of dichlorvos disposed of or on the 

specific disposal method used. 

DICHLORVOS 131 

5. POTENTIAL FOR HUMAN EXPOSURE 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

Dichlorvos is released to the environment solely by human activity. Before the mid-1950s, releases of 

dichlorvos were largely associated with the environmental transformation of the agricultural pesticide 

trichlorfon. Dichlorvos is significantly more volatile than trichlorfon or most other organophosphate 

pesticides. While the relatively high volatility of dichlorvos makes it impractical for application to 

field crops, this property makes the chemical useful as a fogger and fumigant capable of penetrating 

into small interstitial areas in walls and other structural surfaces to kill insects (Hayes 1982). Some of 

the earliest applications were around confined animal-feeding operations to control flies and other 

pests. By the mid-1960s, dichlorvos preparations were developed that could control the release of the 

vapor in a concentration range from 0.015 mg/m3

 (considered the minimum needed to kill flies or 

mosquitoes after an exposure of several hours) to 0.25 mg/m3

. This higher concentration would kill 

insects after exposures of half an hour or less while providing an adequate margin of safety for 

shortterm human exposures (Hayes 1982). 

Some of the earliest applications outside animal agriculture were for the disinsection (to kill insects, 

mites, and other invertebrate pests) of commercial aircraft subject to quarantine requirements when 

crossing international boundaries (Rasmussen et al. 1963); in museum storage areas (Deer et al. 1993); 

and in warehouses, greenhouses, or containerized ships (Hayes 1982). By the late 1960s 

polyvinylchloride plastic resin strips became popular as a way to dispense dichlorvos in a time-release 

fashion. These strips were widely adopted in livestock holding or feeding operations and also were 

widely used in homes. A variety of pest strip products became popular to control insects around kitchens 

or otherhousehold areas, and dichlorvos strips became widely used as an ingredient in pet flea and tick 

collars (Hayes 1982; IARC 1991; PIP-Dichlorvos 1993). During the 1980s, these household uses were 

progressively reduced as the EPA began a Special Review process for existing registered uses of 

dichlorvos. While the Special Review was still ongoing as of the end of 1994, EPA precautionary 

actions by 1988 required household products containing dichlorvos to display the words “DangerPoison.” Manufacturers began switching to other pesticide agents, mostly on a voluntary basis, so that 

by the early 1990s, consumer use of dichlorvos had declined dramatically (EPA 1988a; Mueller 1992; 

PIP-Dichlorvos 1993). Its uses in agriculture and commercial buildings continue. Dichlorvos has also 

found applications in aquaculture to rid fish of various skin parasites (Hoey and Horsberg 1991). In 
DICHLORVOS 132 

5. POTENTIAL FOR HUMAN EXPOSURE 

addition, both dichlorvos and trichlorfon have veterinary and human medicinal uses in the control of 

severe internal and external parasite infestations (IARC 1991; PIP-Dichlorvos 1993). 

Whether applied in a liquid form or dispensed through plastic resin strips or granules, dichlorvos is 

most commonly released to the atmosphere in a gaseous form and will predominate in the vapor phase 

(Eisenreich et al. 1981). Dichlorvos is not expected to undergo degradation from direct photolysis in 

the atmosphere (Gore et al. 1971). While degradation by ozone in the atmosphere is possible, the 

main degradation pathway involves the vapor phase reaction of dichlorvos with photochemically 

produced hydroxyl radicals. The half-life (first-order kinetics) for dichlorvos in the atmosphere has 

been estimated to be less than 2 days (Howard 1991; Kelly et al. 1994). Dichlorvos can be removed 

from the air through rainfall scavenging. When released to water, hydrolysis is the major degradation 

process which proceeds much more rapidly under alkaline pH conditions and with increasing 

temperature. The hydrolysis half-life of dichlorvos in water is highly variable and is dependent both 

on pH and temperature, but is typically on the order of days or weeks (Faust and Suffet 1966; 

Lamoreaux and Newland 1978; Lartiges and Garrigues 1995; Latif et al. 1984). Because of its high 

solubility in water, dichlorvos would not be expected to bioconcentrate in fish or other aquatic life. 

When released to soils, hydrolysis and other non-biological processes account for 70% or more of the 

total degradation of dichlorvos, while bacterial degradation accounts for only 30% (Lamoreaux and 

Newland 1978). In field studies, Menzie (1972) reported a half-life value (first-order kinetics) of 

17 days for dichlorvos in soil (soil type unspecified). Because, dichlorvos does not readily sorb to soil 

particles, spills, or other large amounts of the pesticide, especially when released in a liquid form or 

dissolved in solvent carriers, may migrate through soil profiles or sediments and into groundwater. 

Since dichlorvos will degrade within a few days in the air, surface waters, or wetted soils due 

primarily to hydrolysis reactions, it is not expected to enter into large-scale regional or hemispheric 

fate and transport processes. 

Dichlorvos has not been extensively monitored in most environmental media. It has been detected at 

very low concentrations in outdoor air, but has been detected at higher concentrations-in indoor air 

associated with its use as a fumigant pesticide in homes or during occupational exposures in 

manufacturing and production facilities. It has not been detected in drinking water and no 

environmental monitoring data were found for dichlorvos in surface or groundwater or in soils and 

sediment. Dichlorvos has been detected infrequently and never at concentrations of concern in both 

raw and processed food items. 
DICHLORVOS 133 

5. POTENTIAL FOR HUMAN EXPOSURE 

Since dichlorvos is a breakdown product of trichlorfon and can be generated in many plants through 

the metabolism of the pesticide naled (EPA 1988a; Menzie 1972; PIP-Naled 1994; PIP-Trichlorfon 

1993), it is often difficult to ascertain the original source of the chemical when dichlorvos is detected 

in environmental media. In addition, trichlorfon and naled can be transformed to dichlorvos during 

sample preparation and analysis procedures. The general population may be exposed to dichlorvos 

primarily by inhaling contaminated air or by absorption via dermal exposure during application of 

liquid formulations. Both inhalation of indoor air and direct dermal contact have been identified as 

primary sources of human exposure at the present time. The risk of exposure is greatest to the general 

populations during and/or immediately after its application. Exposures of the general population to 

dichlorvos via consumption of contaminated food and drinking water are negligible to insignificant. 

Because it is rapidly metabolized, dichlorvos has not been detected in blood, adipose tissue, breast 

milk, or any other tissue samples from the general population or from populations with occupational 

exposures. In occupational settings, exposure is via inhalation of contaminated air and/or via dermal 

contact with dichlorvos formulations. 

Dichlorvos has been identified in at least 3 of the 1,428 current or former hazardous wastes sites that 

have been proposed for inclusion on the EPA National Priorities List (NPL) (HAZDAT 1996). 

However, the number of sites evaluated for dichlorvos is not known. The frequency of these sites 

within the United States can be seen in Figure 5-1. 

5.2 RELEASES TO THE ENVIRONMENT 

Releases of dichlorvos are required to be reported under the Superfund Amendments and 

Reauthorization Act (SARA) Section 313; consequently, data are available for this compound in the 

Toxic Release Inventory (TRI) (EPA 1995a). According to the TRI, in 1993 a total of 1,562 pounds 

(709 kg) of dichlorvos were released to the environment from 5 large processing facilities (TR193 

1995). In addition, an estimated 4,660 pounds (2,114 kg) were transferred off-site (TR193 1995). 

Table 5-l lists these releases. The TRI data should be used with caution because only-certain types of 

facilities are required to report (EPA 1995a). This is not an exhaustive list. 

Dichlorvos has been identified in a variety of environmental media collected at 3 of the 1,428 former 

or current NPL hazardous waste sites (HazDat 1996). 


DICHLORVOS 136 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.2.1 Air 

Dichlorvos may be released to the air during production and processing activities or during its various 

use applications as a pesticide. Based on its vapor pressure of 1.2x10-2 mm Hg at 20oC (see 

Table 3-2), a large portion of the dichlorvos contained in plastic or resin strips, or applied in 

concentrated liquid formulations to surfaces within buildings or other enclosures with low humidities 

would be expected to volatilize to the air. However, no data were located providing comprehensive 

estimates of releases to the air. 

According to the TRI, in 1993, releases of 1,307 pounds (593 kg) dichlorvos to the air from 5 large 

processing facilities accounted for about 84% of the estimated total environmental releases (TR193 

1995). Table 5-l lists amounts released from these facilities. The TRI data should be used with 

caution because only certain types of facilities are required to report (EPA 1995a). This is not an 

exhaustive list. 

Dichlorvos has not been found in air samples collected at any of the 3 NPL sites where it was detected 

in some environmental media (HazDat 1996). 

5.2.2 Water 

Dichlorvos may be released to surface water in waste waters generated by its production or fabrication 

into resin strips or other formulations. Some releases to surface water would also occur when 

dichlorvos is used in aquaculture to control fish parasites. Other releases to water might take place as 

the result of spills or other accidents. No data were found providing comprehensive estimates of 

intentional and unintentional releases into water. 

According to the TRI, estimated releases of 5 pounds (2.3 kg) of dichlorvos to surface water from one 

large processing facility in 1993, accounted for about 0.3% of the estimated total environmental 

releases (TR193 1995). Table 5-l lists these releases. The TRI data should be used with caution 

because only certain types of facilities are required to report (EPA 1995a). This is not an exhaustive 

list. 

Dichlorvos has been found in groundwater samples (concentrations unspecified) at 1 of the 3 NPL 

sites where it was detected in some environmental medium (HAZDAT 1996). 
DICHLORVOS 137 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.2.3 Soil 

Dichlorvos may be released to the soil as a result of intentional uses, spills or through waste disposal 

practices associated with its various formulations. According to the TRI, estimated releases of 

250 pounds (113 kg) of dichlorvos to the land from one large processing facilities in 1993 accounted 

for about 16% of the total environmental emissions. In addition, over 4,660 pounds (2,113 kg) were 

disposed of via offsite waste transfer (TR193 1995). The TRI data should be used with caution 

because only certain types of facilities are required to report (EPA 1995a). This is not an exhaustive 

list. 

Environmental releases of dichlorvos to agricultural soils have occurred from its intentional use in 

livestock feeds to control internal parasites and flies (IARC 1979, 1991; OSU 1992) and its use in 

specialty crops (e.g., tobacco and greenhouse-grown food crops) (IARC 1991). Land application of 

the treated livestock manures may contribute to soil releases of dichlorvos (OSU 1992). Any improper 

disposal of plastic resin material wastes containing dichlorvos or other formulations of dichlorvos 

could also release the chemical to soils. The most recent use application data from the mid- to late 

1980’s suggests that agricultural applications of dichlorvos represented 60% of the total annual use of 

dichlorvos in the United States. Commercial, institutional, and industrial uses accounted for 25% of 

annual usage; while domestic uses, including household pest control and pet collars accounted for only 

15% of annual usage (IARC 1991). Releases of dichlorvos to soils in urban areas have occurred from 

its intentional uses in residential, industrial, and commercial areas including food services, food 

manufacturing and processing facilities; in horticultural and turf applications for pest control; and in 

flea collars, room foggers, and no-pest strips. For products composed of polyvinylchloride plastic 

resins impregnated with dichlorvos, such as flea collars, the collar materials were designed to shed off 

small fragments of the plastic material (exfoliation). These small particles tend to spread throughout 

the animal’s coat, which would assist in delivering the pesticide to fleas and other insect parasites. 

Such small particles could also be spread onto floors or land surfaces, where they could be released to 

the soil. Drastic changes in recent use patterns (EPA 1993a) and restrictions on or cancellations of 

some registrations (EPA 1991a) make it difficult to determine the magnitude of current 

uses/applications of dichlorvos are greater in both agricultural and in urban settings 

Dichlorvos has been found in soil samples (concentrations unspecified) at 1 of the 3 NPL sites where 

dichlorvos was detected in some environmental media (HAZDAT 1996). 
DICHLORVOS 138 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.3 ENVIRONMENTAL FATE 

While most initial releases of dichlorvos will be to the air, the solubility of dichlorvos in water will 

quickly lead to its partitioning to water. Once in contact with water. hydrolysis reactions become the 

predominant mechanisms for degradation, with hydrolysis proceeding more rapidly with increasing pH 

and temperatures (Faust and Suffet 1966; Lamoreaux and Newland 1978). In the environment, abiotic 

degradation via hydrolysis is the primary transformation process, although biodegradation by some 

microorganisms also occurs (see Figure 5-2). Dichlorvos shows little tendency to sorb to soil particles 

or bioconcentrate in living tissues, which creates the potential for dichlorvos to leach through soil and 

sediments into groundwater (PIP-Dichlorvos 1993). 

5.3.1 Transport and Partitioning 

Dichlorvos has a high vapor pressure (1.2x10-2 mm Hg) and if released to the atmosphere, it will be 

found predominately in the vapor phase (Eisenreich et al. 1981). Most dichlorvos releases are initially 

intended to reach the air, but if there is high humidity or rain scavenging, dichlorvos will partition into 

water. The Henry’s law constant for dichlorvos has been calculated as 7.01x10-8 atm-m3/mole at 

25 ̊C (see Table 3-2), which is a fairly low value and suggests that dichlorvos, once dissolved in 

water, will remain in aqueous solution for an appreciable period of time. The solubility of dichlorvos 

in water is 16,000 mg/L (Table 3-2), which is quite high compared to other common organophosphate 

pesticides (e.g., <10 mg/L for malathion or parathion and <100 mg/L for diazinon). Based on the 

Henry’s law constant and for aqueous systems with initial dichlorvos concentrations less than the 

saturation levels, the volatilization half-life from a model river was estimated at 57 days, while the 

volatilization half-life from a model pond was estimated at over 400 days (Howard 1991). 

The log Koc (organic carbon partition coefficient) for dichlorvos has been calculated to be 1.45 

(Kenaga 1980), which is very low. This Koc value suggests dichlorvos will not appreciably sorb to 

soil particles; therefore, dichlorvos can be expected to leach through soil columns or sediments and 

into groundwater (Swann et al. 1983). Since natural soils and sediments contain water, hydrolysis 

reactions will also occur as the dichlorvos moves downward through the soil horizon, and this will 

reduce the amount of dichlorvos transported to groundwater. 

 

DICHLORVOS 140 

5. POTENTIAL FOR HUMAN EXPOSURE 

Because of its high water solubility, dichlorvos would not be expected to show a significant tendency 

to bioconcentrate in fish or other aquatic animals. A commonly used quantitative measure of the 

tendency of some chemicals to partition from the water column into the tissues of aquatic organisms is 

the bioconcentration factor (BCF). This BCF value can be empirically determined by measuring the 

chemical concentration in an organism’s tissues after exposing it over a period of time to a specified 

concentration of the chemical in water. The empirical BCF is calculated as the concentration of the 

chemical in an organism divided by the concentration of the chemical in water. BCFs can sometimes 

be estimated based on regression equations developed from data on physical properties such the 

octanol/water partition coefficient and the water solubility. The larger the value of the BCF, the 

greater the tendency for partitioning into the tissues of an organism. No experimental BCF values for 

dichlorvos have been reported for any aquatic species. A calculated BCF of 2.8 has been reported 

(Kenaga 1980), which is intended to be applicable to many fishes. More recently, the EPA’s ASTER 

Toxicology profile database reported a calculated BCF of 1 for the fathead minnow (Pimephales 

promefus) (ASTER 1996). Such BCF values suggest there is no marked tendency for bioaccumulation 

or biomagnification of dichlorvos through the food chain. One short-term exposure study was 

conducted to test the efficacy of dichlorvos as a pest control agent for sea lice on penned salmon. 

Atlantic salmon (Salmo salar) were exposed to dichlorvos at 2 ppm at either 4 or 12 oC for 

60 minutes as a treatment to remove ectoparasitic copepods (Horsberg and Hoy 1990). These authors 

found that at 4 oC, dichlorvos residues averaged 0.094 μg/g (ppm) in muscle and <0.01 μg/g in liver 

tissue immediately post-treatment. At 12 oC, dichlorvos residues averaged 0.046 μg/g (ppm) in muscle 

and 0.041 μg/g (ppm) in liver tissue. At 4 oC, residues in muscle and liver were not detected after 

3 days post-treatment and at 12 oC, residues were not detected in muscle tissue after 1 day 

posttreatmentand in liver tissue 6 days post-treatment. The rapid clearance of dichlorvos from the fish 

tissues was similar to results obtained in other species (see Chapter 2). 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

Dichlorvos does not strongly absorb ultraviolet (UV) light above 240 nm (Gore et al. 1971; Howard 

1991) and is, therefore, unlikely to be subject to direct photolysis in the atmosphere. Based on 

theoretical considerations, dichlorvos may be susceptible to degradation in the air from free radicals 

such as hydroxyl groups or ozone. Figure 5-2 shows the transformation pathways for dichlorvos in the 
 

DICHLORVOS 141 

5. POTENTIAL FOR HUMAN EXPOSURE 

atmosphere. A calculated half-life, assuming first-order kinetics, for a vapor-phase reaction of 

dichlorvos with photochemically produced hydroxyl radicals was reported to be 2 days, assuming an 

atmospheric concentration of 5x105 hydroxyl radicals per cm3 (Howard 1991). With an assumed level 

of 7.0x1011 ozone molecules per cm3, an estimated half-life (first-order kinetics) for dichlorvos of 

320 days was reported (Howard 1991). 

5.3.2.2 Water 

Dichlorvos is highly soluble in water and tends to remain in solution, with very little tendency to sorb 

to sediments. While dichlorvos can re-volatilize to the air, re-volatilization of dichlorvos once it is 

dissolved in water is a fairly slow process. 

When dissolved in water, dichlorvos becomes subject to both abiotic and biological degradation. The 

predominant degradation mechanism is hydrolysis, and dichlorvos is hydrolyzed into dichlorethanol, 

dichloroacetaldehyde, dichloracetic acid, dimethyl phosphate and dimethyl phosphoric acid (WHO 

1989). The hydrolysis reaction is sensitive to pH, with much more rapid degradation taking place at 

higher, more alkaline pH levels. Chemical hydrolysis of dichlorvos in aqueous, buffered, soil-free 

systems showed that hydrolysis did not occur in very acid systems (pH <3.3), but increased with 

increasing pH values (26% in 4 days at pH 6.9), and was most rapid at pH 9.3 (>99% in 2 days). At 

pH values of 2.0, 3.3, 6.2, 6.9, 7.8, 8.2, 8.7, and 9.3, the percent of initial dichlorvos remaining in 

buffered, aqueous solutions after 96 hours was 99, 100, 92, 89, 84, 82, 36, and 10%, respectively 

(Lamoreaux and Newland 1978). Latif et al. (1984)m reported half-life (first-order kinetics) values for 

dichlorvos of 4,620 minutes (3.2 days), 2,100 minutes (1.46 days), 462 minutes (0.32 days), and 

301 minutes (0.2 days) in water at pH 5.4, 6, 7, and 8, respectively. 

In addition to pH, hydrolysis kinetics are affected by temperature. Faust and Suffet (1966) reported 

that the half-life (first-order kinetics) values for dichlorvos in water were 240, 61.5, 17.3, 1.7, and 

0.2 days at 10, 20, 30, 50, and 70 °C, respectively. Lartiges and Garrigues (1995) studied degradation 

of dichlorvos in different types of water (filtered water, natural seawater, natural river water, and 

filtered river water) under different environmental conditions (temperatures of 6 and 22 “C to simulate 

winter and summer conditions, respectively, and pH values ranging from 6.1 to 8.1). The authors 

reported that at the winter temperature, dichlorvos was still present in the filtered water (pH 6.1) after 

180 days. Residues in river water (pH 7.3) and filtered river water (pH 7.3) disappeared after 81 days 
DICHLORVOS 142 

5. POTENTIAL FOR HUMAN EXPOSURE 

and residues in seawater (pH 8.1) disappeared after 34 days. At summer temperatures, dichlorvos 

residues disappeared in filtered water after 81 days. Residues in river water disappeared after 55 days, 

residues in filtered river water disappeared in 34 days, and residues in seawater persisted for 180 days. 

At pH values of 7.8-8.2, reported half-disappearance times were approximately 96 and 48 hours, 

respectively (Lamoreaux and Newland 1978). At pH values of 8.7 and 9.3, the half-disappearance 

time was less than 24 hours and at pH values of less than 6.9, the half-disappearance time was more 

than 96 hours. Therefore, under pH conditions encountered in most natural waters in contact with the 

atmosphere, hydrolysis can degrade dichlorvos at rates considerably more rapid than the rate of 

dichlorvos re-volatilization to the air. Only at low pHs (less than 4) would dichlorvos show 

persistence. The hydrolysis half-life or half-disappearance time in water is highly variable and is 

dependent both on pH and temperature, but is typically on the order of days to weeks. 

Microorganisms found in sewage sludges apparently can biodegrade dichlorvos, but a period of 

acclimation may be needed and the rate of biodegradation may be much less than that from abiotic 

transformation processes (Lieberman and Alexander 1983). Abiotic hydrolysis rates will generally far 

outstrip the biodegradation rate, and the biotic transformations will be sensitive to pH, temperature, 

and the concentrations of dichlorvos or other toxic chemicals present. The environmental 

transformation pathways for dichlorvos in water are shown in Figure 5-2. 

Since the hydrolysis reaction in water is both pH- and temperature-dependent, caution should be 

exercised in making predictions for dichlorvos in groundwater. In groundwater with low pH (pH <4), 

dichlorvos would be expected to persist for moderate periods, with half-disappearance times greater 

than 4 days (PIP-Dichlorvos 1993). 

5.3.2.3 Sediment and Soil 

In soils containing any appreciable amount of moisture, hydrolysis reactions similar to those in 

aqueous solutions are expected to occur (PIP-Dichlorvos 1993), although few quantitative studies of 

half-life or half-disappearance times could be identified in the literature. In field trials, Menzie (1972) 

reported a half-life (first-order kinetics) value for dichlorvos of 17 days; however, the soil type was 

not specified by the author. In laboratory experiments using natural and sterilized Houston black clay 

soils, the rate of dichlorvos disappearance in the soil was related directly to the presence of the 

bacterium Bacillus cereus, the pH of the soil perfusion system, and the extent of dichlorvos adsorption. 
DICHLORVOS 143 

5. POTENTIAL FOR HUMAN EXPOSURE 

Dichlorvos disappearance was most rapid when B. cereus was added to a previously unsterilized soil 

(half-life value of 3.9 days), while under sterile conditions, a half-life value of 10 days was reported 

(Lamoreaux and Newland 1978). Hydrolysis and other non-biological processes accounted for 70% of 

the total degradation of dichlorvos, while bacterial degradation accounted for only 30% in the soil 

perfusion system (Lamoreaux and Newland 1978). 

For sediments, biodegradation processes may often be similar to the results documented for sewage 

sludges. A sewage sludge culture containing the bacterium Pseudomonas aeruginosa and other 

bacteria from the same genus was shown to convert dichlorvos into several metabolites, including 

dichloroethanol, dichloroacetic acid, ethyl dichloroacetate, and inorganic phosphate (Lieberman and 

Alexander 1983). Dichlorvos was still present in the cultures after 7 days of incubation at 29 oC both 

in the presence or absence of microbes. The environmental transformation pathways for dichlorvos in 

soil and sediment are shown in Figure 5-2. Abiotic hydrolytic cleavage of the parent molecule 

presumably gives rise to dichloroacetaldehyde (via rearrangement of l,l-dichloroethenol) and dimethyl 

phosphate. The dichloroacetaldehyde then is converted enzymatically to dichloroethanol, or to 

dichloroacetic acid (Lieberman and Alexander 1983). The dimethyl phosphate is converted to 

inorganic phosphate with monomethyl phosphate being a likely intermediate. 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Dichlorvos has not been routinely included in most national environmental monitoring programs, so 

that broad-based data are lacking for most environmental media. Results from several special studies 

suggest that dichlorvos should not be found above very low levels on a widespread basis in either air 

or in water. Data for soils and sediments are even more limited. When dealing with soils and 

sediments, a complicating factor is that dichlorvos may be found associated with fragments of 

discarded resin strips or in other plastics wastes or containers impregnated with dichlorvos. 

Where dichlorvos is detected in the environment, it may be impossible to determine whether the initial 

release was from dichlorvos directly or from the application of the pesticide trichlorfon which can 

degrade to form dichlorvos or the pesticide naled which can be transformed in some plant tissues to 

dichlorvos. In addition, dichlorvos can be produced from trichlorfon and naled during sample 

preparation and analysis (see Section 6.2). For these reasons, caution must be used in the 

interpretation of data from environmental samples found to contain dichlorvos. Reliable evaluation of 
DICHLORVOS 144 

5. POTENTIAL FOR HUMAN EXPOSURE 

the potential for human exposure to dichlorvos depends in part on the reliability of supporting 

analytical data from environmental samples and biological specimens. In reviewing data on levels 

monitored or estimated in the environment, it should be noted that the amount of the chemical 

identified analytically is not necessarily equivalent to the amount that is bioavailable. 

5.4.1 Air 

Most of the available measurements of dichlorvos in the air have focused on indoor-air settings where 

dichlorvos has been most commonly used as a fumigant-type pesticide agent; however, limited 

information is available for ambient outdoor air. Kelly et al. (1994) reported that dichlorvos 

concentrations measured in 288 samples of ambient outdoor air collected from 2 locations ranged from 

not detected to 150 ng/m3. As part of the Non-Occupational Pesticide Exposure Study based on the 

EPA’s Total Exposure Assessment Methodology (TEAM) approach, dichlorvos was monitored in 

outdoor air samples collected in Springfield, Massachusetts and in Jacksonville, Florida. While 

dichlorvos was not detected in ambient outdoor air in Springfield, Massachusetts, it was detected at 

3.2 ng/m3 in winter samples collected in Jacksonville, Florida (Whitmore et al. 1994). 

Much of the historic indoor-air monitoring literature deals with product uses that have declined 

dramatically, or ceased altogether, since the late 1980s. For instance, air monitoring data were 

gathered while dichlorvos was a major ingredient in pest strips which were widely used in homes, 

hospitals, restaurants, and other public places to kill flies, cockroaches, and other nuisance insects 

(Elgar and Steer 1972; Leary et al. 1974). Other valuable information comes from studies on potential 

occupational exposure to personnel in museums where dichlorvos was used to kill insects in closed 

display cases or storage areas (Deer et al. 1993), exposures to employees at professional pest control 

companies (Wright and Leidy 1980), and exposures to flight crews while it was used as a disinsection 

agent (prophylactic insecticide) in commercial aircraft (Rasmussen et al. 1963). 

By the late 1960s the design of resin strips or application rates of dichlorvos in liquid or fogger 

formulations was guided by the goals of achieving dichlorvos concentrations in the air of at least 

0.015 mg/m3

 for a period of several hours; this goal to achieve good kills of nuisance insects was 

balanced against the rule of thumb that concentrations below 0.25 mg/m3

 provided an adequate margin 

of safety for human health (Hayes 1982). Where adequate precautions are observed, and barring 
DICHLORVOS 145 

5. POTENTIAL FOR HUMAN EXPOSURE 

accidents. concentrations above this 0.25 mg/m3 threshold are uncommon in studies accompanied by 

good sampling programs. 

Results from early work on the use of dichlorvos-impregnated polyvinylchloride resin pest strips for 

insect control in homes in the United Kingdom, Australia, and France suggest that indoor-air 

concentrations in houses that are well ventilated (especially using open windows) will be very low 

(range, 0.01-0.24 μg/L [mg/m3]) (Elgar and Steer 1972). Leary et al. (1974) monitored the 

concentrations of dichlorvos in indoor-room air in homes in Arizona using polyvinylchloride resin 

strips containing dichlorvos. Homes were treated at a rate of one strip per 1,000 cubic feet and 

typically averaged 8-18 strips per residence. One month after installation, new pest strips were placed 

in the kitchen and dining areas at a rate of one strip per 500 cubic feet. Air samples were collected 

prior to installation of the strips and at 1, 2, 3, 4, 6, 7, 10, 13, 16, 21, and 28 days post-application. 

Dichlorvos concentrations in the air peaked at 0.12-0.13 mg/m3 within several days and then declined 

to a plateau level of 0.08-0.09 mg/m3 from day 12 to 28 post-application. The replacement and 

doubling of the number of strips in the dining room and kitchen produced a maximum concentration 

of 0.16 mg/m3 within 2 days and a subsequent decrease to 0.11 mg/m3 by day 15. Removal of all the 

pest strips from the residence resulted in a rapid decline in dichlorvos residues to zero within 17 days. 

In the EPA TEAM study of indoor-air levels of common household pesticides, dichlorvos was 

included as a target analyte, but was not commonly detected in the indoor air of the homes sampled 

(detected in only 1 out of 9 homes sampled) (Lewis et al. 1988). Most recently, as part of the NonOccupational Pesticide Exposure Study based on the EPA’s TEAM approach, dichlorvos was 

monitored in indoor-air samples collected in Springfield, Massachusetts and in Jacksonville, Florida. 

Dichlorvos was detected in ambient indoor air in Springfield, Massachusetts at concentrations of 

4.3 and 1.5 ng/m3

 in spring and winter air samples, respectively. This pesticide was detected at much 

higher concentrations of 134.5, 86.2, and 24.5 ng/m3 in summer, spring, and winter samples, 

respectively, collected in Jacksonville, Florida (Whitmore et al. 1994). 

The highest occupational exposure reported was 3 mg/m3

 (mean concentration of 0.7 mg/m3) that was 

monitored in a vaporizer production plant and its packaging rooms (Menz et al. 1974 in IARC 1991). 

Other valuable information comes from studies on potential occupational exposure to personnel in 

museums where dichlorvos was used to kill insects in closed display cases or storage areas (Deer et al. 

1993), exposures to employees at professional pest control companies (Wright and Leidy 1980), and 
DICHLORVOS 146 

5. POTENTIAL FOR HUMAN EXPOSURE 

exposure to flight crews while it was used as a disinsection agent in commercial aircraft (Rasmussen et 

al. 1963). Air samples were collected in several locations within a museum of natural history’s 

entomological curation area (Deer et al. 1993). The authors reported a significant difference in the 

mean concentrations of dichlorvos in the air collected with the ventilation system on (0.005 mg/m3

) 

and the ventilation system off (0.14 mg/m3

). Ambient air in the storage rooms (where concentrates of 

various chemicals were stored and mixed to appropriate dilutions) and main office areas of four North 

Carolina commercial pest control firms were monitored for dichlorvos for a 4-hour sampling period 

(Wright and Leidy 1980). These authors found that concentrations in the storage rooms averaged 

617 ng/m3

 (range, 147-1,501 ng/m3) and concentrations in the office areas averaged 41 ng/m3 (range, 

19-66 ng/m3

). In addition, mean dichlorvos concentrations of 110 ng/m3 (range, 16-231 ng/m3) were 

detected in the ambient air inside company pickup trucks and vans used by professional pest control 

technicians (Wright and Leidy 1980). The proposed use of dichlorvos as an aircraft disinsectant was 

studied by Rasmussen et al. (1963). Volunteers were exposed to dichlorvos at concentrations varying 

from 0.14 to 0.33 μg/L (mg/m3

) in a setting designed to simulate the maximal exposure that airline 

flight crew personnel could possibly receive during the maximum period of scheduled duty flights 

(39 doses in a 14-day period). 

5.4.2 Water 

Dichlorvos was included as one of 101 pesticide target analytes in EPA’s National Pesticide Survey of 

Drinking Water Wells (EPA PIN 1994). This survey included wells from community systems used in 

towns and cities, non-community systems found in such public places as truck stops, and private 

domestic wells. Dichlorvos was not found above detection limits in any of the drinking water wells 

sampled. While dichlorvos is not ordinarily included in sampling programs for community systems 

that rely on surface water supplies, the nature of the treatment processes used in most community 

systems tends to minimize the possibilities for dichlorvos to persist in the final tap water. In most 

larger community drinking water systems in the United States that use surface water supplies, 

conventional treatment technologies using lime and soda ash will temporarily raise the alkalinity (pH 

>9). These elevated pHs, combined with the ample opportunities for hydrolysis degradation before the 

treated water reaches end users, virtually eliminate any exposure possibilities to dichlorvos in treated 

drinking water. 
DICHLORVOS 147 

5. POTENTIAL FOR HUMAN EXPOSURE 

No other information was found on the concentrations of dichlorvos in surface water or groundwater 

in the United States. While dichlorvos could be released to surface waters during production or on an 

episodic basis as a result of spills, prompt sample collection and analysis would likely be needed to 

document the presence of dichlorvos. For instance, a dichlorvos formulation known as Nuvan® is 

widely used in Europe to control skin parasites in fish culture, especially in the caged cultures of 

Atlantic salmon. In a coastal bay in Ireland, monitoring was carried out during the summer period 

when salmon were being tended in cages in the bay and for a period after the summer to document the 

possible persistence of dichlorvos in seawater and sediments (Tully and Morrissey 1989). In all but 

one of the ambient water samples from the Beirtreach Bay study, dichlorvos levels were below the 

detection limit of 0.02 μg/L (ppb), suggesting that dichlorvos rapidly dissipates or degrades in large 

natural waterbodies. The exceptional seawater sample in which the pesticide was detected, contained 

0.13 μg/L (ppb) of dichlorvos. 

5.4.3 Sediment and Soil 

No information was found on background levels of dichlorvos in either agricultural or urban soils or in 

sediments in the United States. Given the relatively high volatility of dichlorvos combined with its 

low potential to sorb to soil particles, and its rapid degradation via hydrolysis, dichlorvos does not 

appear to be a good candidate analyte for soil or sediment sampling programs. 

Dichlorvos has been identified at unspecified concentrations in soil samples at 1 of the 3 NPL sites 

where it was detected in some environmental media (HazDat 1996). 

5.4.4 Other Environmental Media 

Dichlorvos has been detected in some foods as part of standard FDA residue monitoring or regional or 

state sampling activities using protocols patterned after the FDA methods. FDA regulatory 

surveillance monitoring extends back to the 1970s. The food items sampled include common fruits 

and vegetables, coffee, wine, and milk. In summaries of the FDA pesticide residue monitoring of 

foods, dichlorvos is reported among those chemicals where some detections were documented, but 

never at concentrations of concern. Positive samples have been detected for some food items for 

which tests were performed in the FDA program from 1978 to 1982 (Yess et al. 1991a), from 1983 to 

1986 (Yess et al. 1991b), for 1987 (FDA 1988), 1988 (FDA 1989), 1989 (FDA 1990), 1990 (FDA 

1991), 1991 (FDA 1992), 1992 (FDA 1993), 1993 (FDA 1994), and 1994 (FDA 1995). For chemicals 
DICHLORVOS 148 

5. POTENTIAL FOR HUMAN EXPOSURE 

with such a low incidence of detection, the published literature does not generally record 

concentrations detected, the food items in which the residues were detected or detection limits. 

Concentrations of dichlorvos in ready-to-eat foods were monitored for 10 years from 1982 through 

1991 through the FDA Revised Market Basket Survey (KAN-DO Office and Pesticide Team 1995). 

Dichlorvos was detected in one sample of one food item (rye bread) at a concentration of 0.01 μg/g 

ppm. 

A summary of the results of chemical residue monitoring conducted by 10 state food laboratories from 

1988 to 1989 showed 2 detections of dichlorvos out of 13,085 food items sampled (0.015% positive 

detections), with neither of these detections exceeding any federal or state tolerance limits (Minyard 

and Roberts 1991). A summary of food residue sampling by the State of California included 

dichlorvos in its screening list, but no detections were reported for testing carried out in 1989 

(Okumura et al. 1991). A special study on pesticide residues in infant formulas carried out for the 

National Academy of Sciences included dichlorvos as a target analyte, but no detections were reported 

based on analysis of 24 milk-based and 19 soy-based infant formula samples (Gelardi and Mountford 

1993). Very low percentages of detections and concentrations well below any thresholds of concern 

are typical of food residue monitoring programs in Canada and the United Kingdom (IARC 1991). 

While detections have been documented in food surveys, dichlorvos residues in food are normally 

destroyed by washing and cooking (IARC 1991); therefore, the risk to the general population in the 

United States is insignificant. In a study from Japan, residues of dichlorvos were found on harvested 

rice, where dichlorvos and other pesticide or fumigant agents had been applied to control insects 

during shipping and storage (Nakamura et al. 1993). The levels of dichlorvos decreased during 

storage, falling to below detection levels within 45 days after the initial treatments. In addition, 

ordinary washing and cooking to prepare the rice for human consumption essentially removed all of 

the dichlorvos residues. 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

While no quantitative information is available on the percentage of dichlorvos released to each 

environmental compartment, dichlorvos can be released to any or all environmental media (air, surface 

water, groundwater, and soil). The general population is exposed to dichlorvos primarily through 

inhalation and dermal contact. Exposure to dichlorvos via consumption of contaminated food is 
DICHLORVOS 149 

5. POTENTIAL FOR HUMAN EXPOSURE 

insignificant because daily intakes are extremely low, and washing and general food preparation 

procedures further remove dichlorvos residues (IARC 1991; Nakamura et al. 1993). Based on the 

results of the 2 recent FDA Total Diet Studies conducted in 1991 and 1992, the estimated mean daily 

dietary intakes of dichlorvos were <0.000l, <0.000l, and 0.0001 μg/kg body weight for 

6-l l-month-old infants, 14-16-year-old males, and 60-65year-old women, respectively (FDA 1992). 

Based on the results of the recent analysis of data from the FDA Total Diet Studies conducted from 

1986 to 1991, the estimated mean daily dietary intakes of dichlorvos were <0.000l, <0.000l, and 

<0.000l μg/kg body weight for 6-l l-month-old infants, 14-16-year-old males, and 60-6.5year-old 

women, respectively (FDA 1993). Exposure to dichlorvos via consumption of contaminated drinking 

water also is insignificant. 

The general population is exposed to dichlorvos primarily through inhalation of contaminated indoor 

air either during and/or immediately after application or through use of polyvinylchloride resin strips. 

Exposure would be of most concern in buildings with inadequate or defective ventilation. Since many 

commercial and residential buildings are sprayed with dichlorvos formulations or use pest control 

strips that vaporize dichlorvos, there is the possibility of widespread low-level exposure to many 

individuals in the general population from inhalation of residual vapors in these dichlorvos-treated 

indoor-air spaces. The second major route of exposure to dichlorvos for the general population is 

through direct dermal contact with the chemical spray during domestic applications, contact with 

dichlorvos-treated plant materials such as grass or ornamental plants, or contact with other treated 

surfaces (e.g., furniture) in domestic or office buildings. Through the late 1980s the widespread use 

of dichlorvos in resin strips for the control of insects within houses or other public buildings created 

the potential for widespread low-level exposures to many individuals in the general population. After 

1988, concerns over the carcinogenic potential of dichlorvos led the EPA to require warning labels on 

pest strips. The FDA then disallowed the use of these products in kitchens, restaurants, or other places 

where food is prepared. This led to a dramatic reduction in dichlorvos formulations for home use. As 

of September 28, 1995, the EPA proposed cancellation of dichlorvos for all home uses (pest strips, 

flea collars, room foggers, and on ornamental lawns and plants) and for many commercial and 

industrial uses (TOXLIST 1995). In addition, the EPA proposed that most retained uses be restricted 

to specially trained certified applicators. The current potential for exposure of the general population 

to dichlorvos appears to be very limited compared to past exposures. In addition, if the proposed 

cancellation of all home use and many commercial and industrial uses of dichlorvos becomes final, 

this will further reduce risks to the general population. 
DICHLORVOS 150 

5. POTENTIAL FOR HUMAN EXPOSURE 

Dichlorvos may still be applied by professional exterminators for insect control in buildings (Berteau 

et al. 1989; Gold and Holcslaw 1985; Wright and Leidy 1980) and in turf grass treatments (Goh et al. 

1986). These applications create potential for some exposure for the general population through 

inhalation, dermal contact, and (especially in children) oral intake. These exposure risks would be 

highest for periods immediately following dichlorvos applications and would be of most concern in 

buildings with inadequate or defective ventilation (Gold and Holcslaw 1985). 

Because dichlorvos is metabolized so rapidly by esterases in the liver and blood, it has not been found 

in human adipose tissue, milk, blood or in urine (see Section 2.5). Even the major metabolic products 

of dichlorvos, dimethyl phosphate and the glucuronide conjugate of dichloroethanol, are rapidly 

excreted from the body and will have left the body completely within a day or two of cessation of 

dichlorvos exposure. 

Although many of the uses of dichlorvos have been restricted, occupational exposures may still occur 

among workers at facilities that manufacture or process dichlorvos, among professional exterminators 

or certified pesticide applicators involved in applying dichlorvos, and among workers at hazardous 

waste sites involved in the disposal of dichlorvos. Retained uses under the proposed EPA rule 

(September 28, 1995), would be restricted to trained, certified applicators, thereby eliminating most 

risks associated with application of this pesticide to all but occupational exposures (TOXLIST 1995). 

Dichlorvos is still widely used in agriculture, especially in confined animal breeding and feeding 

operations. Failure to wear protective clothing (especially gloves) or to rinse hands would increase the 

potential risks from dermal exposure for persons handling dichlorvos in concentrated liquid or resinimpregnated forms. Where dichlorvos is applied in concentrated liquid forms in interior spaces with 

poor ventilation (e.g., applications for termite control), inhalation risks could be significant without the 

use of protective clothing and equipment. Gold and Holcslaw (1985) evaluated dermal and inhalation 

exposure of pesticide applicators involved in spraying dichlorvos in domestic residences. Applicators 

wore a one-piece polyester jumpsuit with an open collar and long sleeves, a hard hat, respirator, and 

rubber gloves. The subject applicators were fitted with both inside and outside dermal exposure pads 

placed on the outer clothing and on the skin beneath the clothing. The total exposure calculated for 

the applicators was 0.0284 mg/kg/hour with 0.028 mg/kg/hour coming from dermal exposure and 

0.0004 mg/kg/hour from respiratory exposure. 
DICHLORVOS 151 

5. POTENTIAL FOR HUMAN EXPOSURE 

Information in the National Occupational Exposure Survey (NOES) conducted by NIOSH from 1981 

to 1983 provides estimates of the number of workers and the different types of occupations and 

industries where workers could be potentially exposed to dichlorvos (NOES 1991). The NOES survey 

estimated 24,204 potential occupational exposures. Approximately 95% of these exposures are from 

four Standard Industrial Classification (SIC) codes: (1711) Plumbing, Heating and Air Conditioning; 

(2048) Prepared Feed Products; (2339) Women’s and Misses’ Outerwear; and (7342) Disinfecting and 

Exterminating Services. 

The Occupational Safety and Health Administration (OSHA) has set a Permissible Exposure Limit 

(PEL) of 1.0 mg/m3

 (0.11 ppm) for dichlorvos in the workplace (OSHA 1974). The National Institute 

for Occupational Safety and Health (NIOSH 1992) also recommends an occupational exposure limit 

(time-weighted average [TWA]) of 1.0 mg/m3

 based on a 10-hour average workday and has 

designated a concentration exceeding 200 mg/m3 as immediately dangerous to life and health (NIOSH 

1990). The American Conference of Governmental Industrial Hygienists (ACGIH) recommends a 

Threshold Limit Value (TLV-TWA) of 0.90 mg/m3 (skin) for occupational exposures (ACGIH 1994). 

The notation “skin” refers to the potential contribution to the overall exposure by the cutaneous route, 

including mucous membranes and the eyes, either by contact with vapors or by direct skin contact 

with dichlorvos. The use of this notation is intended to alert the reader that air sampling alone is 

insufficient to accurately quantitate exposure and that measures to prevent significant cutaneous 

absorption many be required (ACGIH 1994). 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

In addition to those individuals occupationally exposed to dichlorvos identified in Section 5.5, several 

groups within the general population may receive potentially higher inhalation exposures to 

dichlorvos. These groups include individuals living near facilities where dichlorvos is produced or 

processed and those individuals living near the 3 NPL hazardous waste sites where this compound is 

present. Although dichlorvos is not tightly bound to soil particles, ingestion of dichlorvos 

contaminated soil or soil where polyvinylchloride resin strips have been disposed of, may be a route of 

exposure particularly for children living in areas near production facilities or near hazardous waste 

sites. Ingestion of contaminated groundwater by individuals living in the vicinity of hazardous waste 

sites may be another possible source of exposure for both adults and children if these individuals use 

untreated well water as their primary source of drinking water. 
DICHLORVOS 152 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.7 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with 

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of dichlorvos is available. Where adequate information is 

not available, ATSDR, in conjunction with the NTP, is required to assure the initiation of a program 

of research designed to determine the health effects (and techniques for developing methods to 

determine such health effects) of dichlorvos. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will 

be evaluated and prioritized, and a substance-specific research agenda will be proposed. 

5.7.1 Identification of Data Needs 

Physical and Chemical Properties. The relevant physical and chemical properties of dichlorvos 

(listed in Table 3-2), are generally known (ASTER 1996; Bowman and Sans 1983; Kenaga 1980; 

Kowamoto and Urano 1989; Merck 1989; Sunshine 1969; Worthing 1983). No major data needs were 

identified for physical and chemical properties. 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are 

required to submit chemical release and off-site transfer information to the EPA. The Toxics Release 

Inventory (TRI), which contains this information for 1993, became available in May of 1995. This 

database will be updated yearly and should provide a list of industrial production facilities and 

emissions. 

As with most pesticide agents, it is virtually impossible to make quantitative estimates of dichlorvos 

production, use, disposal, and imported and exported volumes. While regulations govern the 

registration and labeling of pesticide agents, no national statistics are maintained on the amounts sold 

or actually used. For pesticide agents where production has shown major declines and there are few 
DICHLORVOS 153 

5. POTENTIAL FOR HUMAN EXPOSURE 

remaining plants manufacturin g the pesticide for domestic use, confidentiality considerations may 

prevent the public reporting of production data. Import and export statistics are generally maintained 

only for very broad categories of insecticides and not for specific pesticide agents. Under the federal 

Resource Conservation and Recovery Act (RCRA) system, pesticides are similarly covered under very 

broad waste categories that make it virtually impossible to track disposal patterns for specific pesticide 

agents. This presents some fundamental problems in making more than the most general sorts of 

exposure assessments. While some historic information is available on production and use (Cremlyn 

1978; EPA 1976, 1987b, 1988a. 1991a, 1993a, 1994a; Gianessi 1986; IARC 1979, 1991; Marking 

1992; Menz et al. 1974 in IARC 1991; PIP-Dichlorvos 1993; WHO 1989), current information for any 

of these categories (production. use, import/export, and disposal) is considered a major data need. 

This information would be helpful in evaluating potential exposures and risks to human health. 

Environmental Fate. Empirical data on the environmental fate of dichlorvos are almost 

completely lacking. Because dichlorvos tends to undergo rapid hydrolysis (Howard 1991; PIPDichlorvos 1993) under typical environmental conditions, it has been assumed to degrade rapidly and 

to pose few risks to humans. Dichlorvos is an environmental degradation product of the pesticide 

trichlorfon and can also be metabolized in many plants from the pesticide naled (EPA 1988a; Menzie 

1972; PIP-Naled 1994; PIP-Trichlorfon 1993). In addition, the pesticides trichlorfon and naled can 

decompose to dichlorvos during sample preparation and analysis. These two factors add further 

complications to interpreting detections of dichlorvos in environmental media. Since dichlorvos found 

at NPL or other waste sites may be in the form of discarded resin-plastic materials, further fate and 

transport research would be valuable in explaining how the dichlorvos impregnated in such plastics is 

actually released to air, water, or soils. 

Bioavailability from Environmental Media. Dichlorvos can be absorbed following inhalation of 

contaminated workplace air, through derrnal contact, and through consumption of contaminated food 

or water. Exposure to dichlorvos through inhalation or dermal contact directly with liquid formulations 

or with dichlorvos pest strips and residues on treated surfaces are probably the largest sources of 

exposure for the general population. Exposure to dichlorvos through ingestion of contaminated 

drinking water is expected to be insignificant since the compound is readily hydrolyzed in water, 

except at very low pH values (pH <4). Well water from areas around hazardous waste sites where 

dichlorvos has been detected should be monitored to determine whether exposures are insignificant. 

Exposure to dichlorvos through ingestion of contaminated foods also is expected to be insignificant 
DICHLORVOS 154 

5. POTENTIAL FOR HUMAN EXPOSURE 

since this pesticide is rarely found in raw foods at concentrations of concern and because routine food 

preparation procedures (i.e., washing and cooking) further reduce dichlorvos residues (IARC 1991; 

Nakamura et al. 1993). The lack of information on current levels of use makes precise exposure 

assessments extremely difficult. Since resin-strips are no longer used in households, risks to the 

general population are likely to have declined since the mid-1980s. Risks may still remain for persons 

in some occupations (e.g., professional pesticide applicators or workers in confined animal-feeding 

operations where dichlorvos is still used for pest control, and in veterinary applications) and for those 

people living near production or processing facilities or those living near waste disposal sites. The 

main occupational exposure pathways are from inhalation or dermal exposures. Although dichlorvos is 

not tightly bound to soil particles, dermal contact with or ingestion of dichlorvos contaminated soil or 

soil where polyvinylchloride resin strips have been disposed of, may be a route of exposure 

particularly for children living in areas near hazardous waste sites. Improvements in current estimates 

of the numbers of people in these various groups is a major data need. Information regarding the 

bioavailability of dichlorvos from dermal contact and from ingestion of soil-bound dichlorvos, 

particularly in children, and the levels of dichlorvos in contaminated groundwater would be helpful in 

assessing health risks to populations living near hazardous waste sites. 

Food Chain Bioaccumulation. While virtually no experimental data could be identified, the 

BCF values calculated based on the physical and chemical properties of dichlorvos strongly suggest 

that there is very limited potential for bioaccumulation or biomagnification in the food chain (ASTER 

1996; Kenaga 1980). Additional experimentally determined estimates of BCF in edible fish or 

shellfish would be helpful in verifying that bioaccumulation of dichlorvos is not an important process 

in the transfer of residues to humans. 

Exposure Levels in Environmental Media. Dichlorvos is not commonly included in routine 

monitoring programs for air, water or soil. Additional monitoring data, at least in the form of national 

surveys such as the EPA’s Pesticides in Groundwater project, would be very valuable in assessing 

ambient dichlorvos concentrations. Dichlorvos has been included in the FDA food surveillance 

program, and these data suggest there is no significant risk to the general U.S. population from eating 

dichlorvos in the food supply (FDA 1989, 1990, 1991, 1992, 1993, 1994c, 1995; KAN-DO Pesticide 

Team 1995). Available information also suggests there are few risks associated with ingestion of 

treated drinking water from larger community systems because water treatment procedures operate in 

alkaline conditions that would facilitate more rapid hydrolysis of dichlorvos. Exposures to dichlorvos 
DICHLORVOS 155 

5. POTENTIAL FOR HUMAN EXPOSURE 

from ingestion of contaminated groundwater from domestic wells are not well known. Additional 

monitoring data are needed to determine dichlorvos concentrations in domestic well water, especially 

from wells near waste disposal sites where dichlorvos has been identified and where the well water is 

being used as a drinking water source by local residents. This information is needed to determine 

whether any additional risks exist for populations living in proximity to these hazardous waste sites. 

Since dichlorvos found at NRL or other waste sites may be in the form of discarded resin-plastic 

materials, further research on the degradation of dichlorvos impregnated in such plastics would be 

useful in assessing exposure levels particularly in soil and sediment. 

Exposure Levels in Humans. There are no data concerning levels of dichlorvos in human 

tissues (including adipose tissues, blood, milk, or urine) for members of the general U.S. population or 

in populations with occupational exposure to dichlorvos. Dichlorvos has not been detected in the 

human body and only rarely in animals because of its rapid metabolism by esterases in the liver and 

blood. Additional information on exposure levels in the general population and in individuals in 

occupational settings would be useful. This information is necessary for assessing the need to conduct 

health studies on these populations. 

Exposure Registries. No exposure registries for dichlorvos were found. This substance is not 

currently one of the compounds for which a subregistry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for 

subregistries to be established. The information that is amassed in the National Exposure Registry 

facilitates the epidemiological research needed to assess adverse health outcomes that may be related 

to exposure to this substance. 

5.7.2 Ongoing Studies 

The U.S. Department of Agriculture (USDA) is currently sponsoring several research projects related 

to migration of the pesticide trichlorfon following application to turfgrass (FEDRP 1996). This 

research is important in studying the movement of dichlorvos which is a major degradation product of 

trichlorfon. Researchers at the New York Agricultural Experimental Station in Geneva, New York are 

conducting experiments to determine the extent of downward movement of the pesticide trichlorfon 

commonly applied to creeping bentgrass turf grown on various soil types. Leachates and soils from 
DICHLORVOS 156 

5. POTENTIAL FOR HUMAN EXPOSURE 

the Automated Rain Exclusion System for Turfgrass Studies in Ithaca, New York will be analyzed for 

chemical residues. 

Researchers at Cornell University in Ithaca, New York are conducting experiments to determine the 

extent of downward movement of the pesticide trichlorfon applied to several major soil types using 

normal management practices. The leaching characteristics of trichlorfon will be studied on creeping 

bentgrass turf plots. Leachates and soils from the Automated Rain Exclusion System for Turfgrass 

Studies in Ithaca, New York will be analyzed for chemical residues. 

Researchers at Pennsylvania State University in University Park, Pennsylvania are conducting 

experiments to determine the extent of downward movement of the pesticide trichlorfon applied to 

several major soil types using normal management practices. The runoff and leaching characteristics 

of trichlorfon will be studied on creeping bentgrass turf plots. Leachates and soils from the 

Automated Rain Exclusion System for Turfgrass Studies in Ithaca, New York will be analyzed for 

chemical residues. 

Researcher at the University of Massachusetts at Amherst, Massachusetts are conducting experiments 

to determine the rate of volatile loss and the amount of dislodgeable residues from pesticide-treated 

turfgrass. One of the pesticides being studied is trichlorfon. The fate of the pesticide will be 

evaluated. Concentrations of trichlorfon will be measured in air samples and in dislodgeable residues 

from a one square foot area of treated sod. Preliminary investigations have found that dichlorvos 

concentrations in air may be of concern even three days post-application of trichlorfon on the grass. 
DICHLORVOS 157 

6. ANALYTICAL METHODS
 

The purpose of this chapter is to describe the analytical methods that are available for detecting, and/or 

measuring, and/or monitoring dichlorvos, its metabolites, and other biomarkers of exposure and effect 

to dichlorvos. The intent is not to provide an exhaustive list of analytical methods. Rather, the 

intention is to identify well-established methods that are used as the standard methods of analysis. 

Many of the analytical methods used for environmental samples are the methods approved by federal 

agencies and organizations such as EPA and the National Institute for Occupational Safety and Health 

(NIOSH). Other methods presented in this chapter are those that are approved by groups such as the 

Association of Official Analytical Chemists (AOAC) and the American Public Health Association 

(APHA). Additionally, analytical methods are included that modify previously used methods to obtain 

lower detection limits, and/or to improve accuracy and precision. 

6.1 BIOLOGICAL SAMPLES 

Analytical methods for the determination of dichlorvos in human biological samples are listed in 

Table 6-l. 

Dichlorvos can be recovered from biological media through extraction with an organic solvent 

(Nordgren 1981; Tewari and Harpalani 1977; Tewari et al. 1974), through the use of solid phase 

extraction (SPE) (Kawasaki et al. 1992; Liu et al. 1989), or through a clean-up of the matrix with no 

additional isolation steps (Unni et al. 1992). Determination is via gas chromatography (GC) with mass 

spectrometry (MS), electron capture (ECD), nitrogen-phosphorus (NPD), flame photometric (PPD), or 

flame ionization (FID) detectors, high performance liquid chromatography (HPLC) with 

spectrophotometric detection, or thin layer chromatography (TLC). Limits of detection are generally 

in the sub-ppm range. Reported recoveries for dichlorvos range from 74 to 85% based on 

measurements of dichlorvos made immediately after addition of the compound to the tissue or plasma. 

Dichlorvos is formed in viva from trichlorfon (metrifonate; (o,o-dimethyl-(1 -hydroxy-2,2,2-

trichloroethyl) phosphonate), a drug used to treat schistosomiasis (Nordgren 1981; Unni et al. 1992). In 

addition, the pesticides naled (o,o-dimethyl-o-( 1,2-dibromo-2,2-dichloroethyl)phosphate) and 

trichlorfon can decompose to dichlorvos during sample preparation (see Section 6.2). In light of these 


DICHLORVOS 160 

6. ANALYTICAL METHODS 

transformations, caution must be used in the interpretation of data from samples found to contain 

dichlorvos. It is quite possible that the measured dichlorvos did not arise from exposure to dichlorvos, 

but rather from exposure to trichlorfon or naled. 

6.2 ENVIRONMENTAL SAMPLES 

Analytical methods for the determination of dichlorvos in environmental samples are listed in 

Table 6-2. 

Most of the methods for the determination of dichlorvos in air are based on the interaction of the 

vapor with an adsorbent as air is drawn through a sorbent tube with a sampling pump. Early methods 

used potassium nitrate for adsorption followed by recovery of dichlorvos via elution with hexane 

(Bryant and Minett 1978), or dissolution in water of the salt containing adsorbed dichlorvos (Heuser 

and Scudamore 1966). The dichlorvos in the resulting solution was then determined. The relatively 

high water solubility of dichlorvos allowed for its collection in water as an air sample was bubbled 

through a Drechsel bottle (Elgar and Steer 1972). Quantitation was often based on the ability of the 

desorbed sample to inhibit the enzyme cholinesterase (Elgar and Steer 1972; Heuser and Scudamore 

1966). More recent methods use polymeric sorbents such as polyurethane foam (PUP) (EPA 1988d), 

SPE disks (Markell et al. 1994), XAD (Brouwer et al. 1994; OSHA 1986) or Tenax TA (Roinestad et 

al. 1993). Analyte recovery was via extraction of the polymeric material with organic solvent, and 

determination typically by GC. With very few exceptions, detection was achieved using the nitrogen/ 

phosphorus thermionic detector (NPD), the flame photometric detector (FPD) in the phosphorus mode, 

or the electron capture detector. Confirmation was obtained using MS. Limits of detection were often 

in the sub-ppb and sub-ppt range (OSHA 1986; Roinestad et al. 1993). 

Methods for the recovery of dichlorvos from water, soil, and wastes are based on liquid/liquid 

extraction (ASTM 1994; EPA 1991b, 1992a, 1992b; Kadokami et al. 1991) or SPE (DiCorcia et al. 

1993; Wang and Huang 1994) followed by extract volume reduction or solvent exchange followed by 

volume reduction. Supercritical fluid extraction (SFE) also holds promise for the extraction of 

dichlorvos from soils (Lopez-Avila et al. 1990; Snyder et al. 1992) or as a means to recover 

dichlorvos from an SPE cartridge (Barnabas et al. 1994). The water solubility of dichlorvos can often 

result in poor recoveries from aqueous matrices (EPA 1992b); salt is often added during extraction to 

favor dichlorvos partition into the organic phase (ASTM 1994; EPA 1991b; Kadokami et al. 1991). 







DICHLORVOS 168 

6. ANALYTICAL METHODS 

The pH of liquid samples is often adjusted to 7 prior to extraction to minimize the hydrolysis of 

dichlorvos during extraction (ASTM 1994; EPA 1991b, 1992a, 1992b). 

The determination of dichlorvos in the resulting extracts is typically by GC with selective detection 

such as NPD, FPD, or MS, although HPLC with ultraviolet (UV) absorbance detection (DiCorcia et al. 

1993) and TLC have also been reported (Askew et al. 1969; Shevchuk et al. 1987). Limits of 

detection range from low parts per trillion (ppt) (ng/L) for relatively clean water (ground, drinking 

water) to the mgkg (ppm) range for non-water-miscible wastes. 

Electrochemical sensors have been developed and applied in a research setting. Potentiometric sensors 

(Imato and Ishibashi 1995; Ivnitskii and Rishpon 1994) and amperometric sensors (Hartely and Hart 

1994; Martorell et al. 1994) based on immobilized acetyl- or butyrylcholinesterase have been 

described. Inhibition of the enzyme activity in proportion to the concentration of organophosphorus 

pesticides, including dichlorvos, in water is the basis of their operations. Sensitivities as low as submicromolar concentrations of dichlorvos in water have been demonstrated. However, they are not 

specific to dichlorvos and have not undergone testing for ruggedness in environmental use. 

Significant losses of dichlorvos can occur during preparation of samples for analysis. Some types of 

boiling chips have been found to facilitate the decomposition of dichlorvos during extract volume 

reductions (Hsu et al. 1988). The volatility of dichlorvos can also result in losses during volume 

reductions of extracts (Holland 1977; Lartiges and Garrigues 1993) so care must be taken to avoid 

taking extracts to dryness during solvent exchange operations. Loss of dichlorvos can also result from 

improper storage of soil samples (Snyder et al. 1992) prior to extraction; samples should be kept cold 

and processed as soon as possible. The storage of SPE cartridges onto which dichlorvos has been 

adsorbed, as after collection of dichlorvos from water, can also result in losses (Lacorte et al. 1995). 

It is very important that appropriate control samples be used and that the method be validated prior to 

its use in a critical study. 

Dichlorvos can be produced from other chemicals during sample preparation and analysis. Trichlorfon 

rearranges and is dechlorinated in acidic, neutral, or basic media to form dichlorvos and hydrochloric 

acid (EPA 1992b). In addition, naled can be converted to dichlorvos during sample workup (EPA 

1992b). The analyst must be aware that such transformations can lead to incorrect or misleading 

results for dichlorvos quantitations. High temperatures in the GC injector or oven can facilitate the 
DICHLORVOS 169 

6. ANALYTICAL METHODS 

transformation of naled and trichlorfon to dichlorvos (EPA 1992b; Yamashita et al. 1991) and lead to 

incorrect quantitative results for dichlorvos. The use of cool on-column injection can minimize 

injector-related transformations of trichlorfon (Yamashita et al. 1991), but transformation on-column 

can still occur and can be minimized through the use of short, thin-film columns to facilitate elution at 

lower temperatures (FDA 1994a). 

Dichlorvos residues have been determined in a variety of foods including produce, grain, meats, milk, 

honey, and wine. Dichlorvos is most easily recovered from low-moisture foods, such as grain, by 

homogenization with an organic solvent (Crisp and Tarrant 1971). For non-fatty, high moisture foods, 

the sample is typically homogenized in the presence of a salt such as sodium sulfate and an organic 

solvent (Agiiera et al. 1993; FDA 1994a; Ministry of Agriculture, Fisheries and Food 1977; Roos et al. 

1987; Thier and Zeumer 1987; Zegers et al. 1994). The salt serves to absorb water and to favor the 

partition of dichlorvos into the organic phase. In some cases, homogenized sample is mixed with 

Florisil, as for produce in Kadenczki et al. (1992), or silicic acid, as for milk in Ivey and Clabom 

(1969) to obtain a free-flowing powder that is packed into a column and eluted with organic solvent to 

recover dichlorvos. Column chromatography (gel permeation, adsorption) is often used to remove 

impurities that could interfere with analysis. For fatty foods such as meats, additional chromatographic 

or solvent partition clean-up operations are needed to remove the fats that can foul chromatographic 

systems. Careful use of controls and method validation is indicated because of the sample losses that 

can occur during clean-up. For example, significant losses of dichlorvos occur during clean-up steps 

in FDA PAM1 Method 304 for fatty foods (FDA 199413). Emey (1995) hypothesizes that loss of 

dichlorvos during sample workup of skim milk arises from lack of a fatty “keeper” and subsequent 

volatilization losses of the analyte. The transformation products of dichlorvos, including 

desmethyldichlorvos, dichloroacetaldehyde, dichloroethanol, and dichloroacetic acid have also been 

recovered from pork and other pig tissues and fluids (Schultz et al. 1971). In this case, the chemical 

derivatives of the transformation products are formed before chromatographic analysis. The same 

concerns about chemical transformations during sample preparation discussed above also apply to 

foods. 

Dichlorvos is most often determined in the extracts using GC with selective detection, although one 

method was reported that employed supercritical fluid chromatography (SFC) (Zegers et al. 1994). 

Limits of detection for dichlorvos in produce were reported to be in the ppm to low-ppb range and 

those in animal samples were reported to be in the high-ppb to low-ppb range. 
DICHLORVOS 170 

6. ANALYTICAL METHODS 

6.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with 

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of dichlorvos is available. Where adequate information is 

not available, ATSDR, in conjunction with the NTP, is required to assure the initiation of a program 

of research designed to determine the health effects (and techniques for developing methods to 

determine such health effects) of dichlorvos. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will 

be evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. Exposure to dichlorvos can 

occur from environmental exposure as a result of contacting air (inhalation), water (ingestion), food 

(ingestion), or dermal contact. Methods exist for the determination of dichlorvos in blood and tissues; 

limits of detection in plasma have been reported to be 40 ppb with 8% relative standard deviation 

(RSD) (Unni et al. 1992) and 2 ppb (Kawasaki et al. 1992). Their utility is limited, however, because 

of the short half-life of dichlorvos in these media (Blair et al. 1975; Unni et al. 1992). Dimethyl 

phosphate is more persistent in urine (Das et al. 1983; Takamiya 1994), but is not specific to 

dichlorvos; any organophosphate that contains a dimethyl phosphate moiety will produce dimethyl 

phosphate upon hydrolysis. Dimethyl phosphate can be detected in urine down to concentrations of 

0.02 ppm, although a high (149%) recovery was reported at a concentration of 0.50 ppm (Takamiya 

1994). The bias at the limit of detection is unclear. Additional information would make the method 

more meaningful. Additional transformation products include dichloroacetaldehyde, dichlorethanol, 

and dichloracetic acid (Schultz et al. 1971), which are specific to dichlorvos exposure. 

Dichloroethanol has been detected in human urine after treatment with more glucuronidase followed 

by GC (Hutson and Hoadley 1972b). However, an endogenous interferant resulted in a large 

measurement error and limited application of the method to high exposures. Additional method work 
DICHLORVOS 171 

6. ANALYTICAL METHODS 

could improve that situation. Exposures to naled and trichlorphon, two organophosphates that are 

converted in the body to dichlorvos, would also have to be ruled out before a definitive determination 

of dichlorvos exposure could be made. 

The most sensitive biomarker for exposure to dichlorvos is inhibition of the activity of serum 

cholinesterase. This enzyme is related to the target for dichlorvos toxicity, neural acetylcholinesterase. Neural and erythrocyte acetylcholinesterase are produced by the same gene and a reasonable 

correlation exists in animal studies between neural and erythrocyte acetylcholinesterase inhibition 

resulting from organophosphate exposure. Volunteers who consumed 0.033 mg/kg/day dichlorvos over 

a 21-day period demonstrated a 30% inhibition of serum cholinesterase activity without effect on 

erythrocyte acetylcholinesterase activity or clinical signs of organophosphate neurotoxicity (Boyer et 

al. 1977). 

Serum cholinesterase and erythrocyte acetylcholinesterase are measured by the spectrophotometric 

method of Ellman (Ellman et al. 1961). Blood samples are centrifuged and aliquots of serum are used 

for assay. Erythrocyte acetylcholinesterase can be determined by lysing the pellet in hypotonic 

solution and washing the erythrocyte membranes where the enzyme is located. Samples are added to 

buffer containing the substrate acetylthiocholine and 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB). The 

product of the reaction, thiocholine, reacts with the DTNB to give a yellow product which is measured 

spectrophotometrically. Kits are available from a number of manufacturers to perform these assays 

using autoanalyzer equipment. 

Normal ranges for enzyme activity have been established. Dichlorvos inhibits serum cholinesterase at 

levels that have no effect on erythrocyte acetylcholinesterase in most species, including humans 

(Hayes 1982). Given the variability in normal activities in humans (especially for serum cholinesterase), 

confirmation of exposure is best established by repeated determinations demonstrating an increase in 

activity to a constant level after exposure has ceased. Information on cholinesterase activities can be 

combined with the measurement of other transformation products to increase the certainty that 

exposure to dichlorvos has occurred. 

Methods for Determining Parent Compounds and Degradation Products in 

Environmental Media. If an MRL of 0.00006 ppm (0.0005 mg/m3

) for chronic inhalation 

exposure is assumed, an analytical method for dichlorvos in air must have a limit of detection of 
DICHLORVOS 172 

6. ANALYTICAL METHODS 

0.00006 ppm (0.0005 mg/m3) or less. Limits of detection for dichlorvos in air of 1 ng/m3 (0.11 ppt) 

(Roinestad et al. 1993) and 0.0019 mg/m3 (OSHA 1986) have been reported. The Roinestad method 

is sufficiently sensitive to permit determination of potential inhalation exposures below the MRL. No 

new methods are needed. 

An oral MRL for chronic exposure to dichlorvos has been established as 0.0005 mg/kg/day which 

corresponds to a dose of 0.035 mg/day for a 70-kg person. If a 2 L/day consumption of water is 

assumed, this corresponds to a required limit of detection (LOD) of 0.0175 mg/L (0.0175 ppm, weight 

per volume [w/v]) for drinking water. Most of the methods for drinking water report LODs in the 

low-ppb range (ASTM 1994; DiCorcia et al. 1993; EPA 1991b) and are adequate. No new methods 

for drinking water are needed. If a 2 kg/day consumption of food is assumed, this corresponds to a 

needed LOD in food of 0.0175 mg/kg (0.0175 ppm, weight per weight [w/w]). The FDA method for 

dichlorvos in non-fatty foods (FDA 1994a) has an LOD of 20 ppb and is just outside of the adequate 

range. The methods of Crisp and Tarrant (1971) for wheat (LOD=0.005 ppm) and Kadenczki et al. 

(1992) for dichlorvos on various crops (LOD=5 ppb) are adequate. However, methods for dichlorvos 

in fatty foods are more problematic. The method of Schultz et al. (1971) for dichlorvos in pig tissue 

has an LOD of 0.05-0.1 ppm and is not adequate. The FDA method for fatty foods requires 

additional column chromatography clean-up and is not satisfactory for dichlorvos (FDA 1994b). Thus, 

additional methods for fatty foods are needed. Virtually no information was found on methods for 

environmental transformation products. Methods are needed for these compounds in foods. 

6.3.2 Ongoing Studies 

No ongoing research was found in which new methods for detecting dichlorvos are being developed. 
DICHLORVOS 173 

7. REGULATIONS AND ADVISORIES
 

The international, national, and state regulations and guidelines regarding dichlorvos in air, water, and 

other media are summarized in Table 7- 1. 

ATSDR has derived an acute-duration inhalation minimal risk level (MRL) of 0.002 ppm for 

dichlorvos based on a NOAEL of 1.82 mg/m3 dichlorvos for inhibition of erythrocyte acetylcholinesterase (biomarker for dichlorvos neurotoxicity) in a study in male Sprague-Dawley rats which were 

exposed to atmospheres containing dichlorvos over a 3-day period (Schmidt et al. 1979). 

ATSDR has derived an intermediate-duration inhalation MRL of 0.0003 ppm for dichlorvos based on a 

NOAEL of 0.03 ppm for the neurological effect of brain acetylcholinesterase inhibition in a study in 

pregnant Carworth E rats exposed to atmospheres containing dichlorvos during their 20-day gestation 

period (Thorpe et al. 1972). 

ATSDR has derived a chronic-duration inhalation MRL of 0.00006 ppm for dichlorvos based on a 

NOAEL of 0.006 ppm in male rats for brain and erythrocyte acetylcholinesterase in a 2-year 

inhalation study in Carworth E rats (Blair et al. 1976). Females at this dose had a 12% reduction in 

erythrocyte acetylcholinesterase; this is also a NOAEL, since erythrocyte acetylcholinesterase 

inhibition of 20% or less is not considered an adverse effect. 

ATSDR has derived an acute-duration oral MRL of 0.004 mg/kg/day for dichlorvos based on a 

LOAEL of 4 mg/kg/day for inhibition of brain acetylcholinesterase based on a 14-day study in male 

Sprague-Dawley rats that received 4 mg dichlorvos daily by gavage in corn oil (Teichert et al. 1976). 

ATSDR has derived an intermediate-duration oral MRL of 0.003 mg/kg/day for dichlorvos based on a 

NOAEL of 0.033 mg/kg/day for inhibition of erythrocyte acetylcholinesterase in a 21-day study in 

male volunteers who consumed 0.033 mg/kg/day in either a capsule form or in a 3-ounce container of 

gelatin at meals (Boyer et al. 1977). 

ATSDR has derived a chronic-duration oral MRL of 0.0005 mg/kg/day for dichlorvos based on a 

NOAEL of 0.05 mg/kg/day for inhibition of brain acetylcholinesterase in a 52-week feeding study in 

dogs which consumed 0.05 mg/kg/day by gelatin capsule (AVMAC Chemical Co. 1990; IRIS 1995). 
DICHLORVOS 174 

7. REGULATIONS AND ADVISORIES 

The EPA has established a reference concentration (RfC) of 0.0005 mg/m3 (0.0006 ppm) for 

dichlorvos (IRIS 1996). The EPA has established a reference dose (RfD) of 0.0005 mg/kg/day for 

dichlorvos (IRIS 1996). 

The EPA has identified dichlorvos as a probable human carcinogen (IRIS 1995). The International 

Agency for Research on Cancer (IARC) has determined that dichlorvos is possibly carcinogenic to 

humans (IARC 1991). In studies conducted under the National Toxicology Program (NTP), female 

mice showed some evidence of carcinogenic effect; male rats and mice some evidence; and female rats 

equivocal evidence (NTP 1995). 

Dichlorvos is one of the chemicals regulated under “The Emergency Planning and Community Rightto-Know Act of 1986” (EPCRA) (EPA 1987b). Section 313 of Title III of EPCRA requires owners 

and operators of certain facilities that manufacture, import, process, or otherwise use the chemicals on 

this list to report annually their release of those chemicals to any environmental media. 

OSHA requires employers of workers who are occupationally exposed to dichlorvos to institute 

engineering controls and work practices to reduce and maintain employee exposure at or below 

permissible exposure limits (PEL). The employer must use engineering and work practice controls, if 

feasible, to reduce exposure to or below an g-hour TWA of 1 mg/m3

. Respirators must be provided 

and used during the time period necessary to install or implement feasible engineering and work 

practice controls (OSHA 1974). 

Dichlorvos is designated a hazardous substance and subject to regulations implementing Section 311 

of the Federal Water Pollution Act (EPA 1978) and Section 311 of the Clean Water Act (EPA 1986). 




DICHLORVOS 179 

8. REFERENCES
 

*Abdi YA, Villen T. 1991. Pharmacokinetics of metrifonate and its rearrangement product dichlorvos 

in whole blood. Pharrnacol Toxicol 68(2): 137-139. 

*ACGIH. 1994. 1994- 1995 Threshold Limit Values for chemical substances and physical agents and 

biological exposure indices. American Conference of Governmental Industrial Hygienists. Cincinnati, 

OH. 

“Aguera A, Contreras M, Femandez-Alba AR. 1993. Gas chromatographic analysis of 

organophosphorus pesticides of horticultural concern. J Chromatogr A 655(2):293-300. 

*Ali SF, Chandra 0, Hasan M. 1980. Effects of an organophosphate (dichlorvos) on open field 

behavior and locomotor activity: correlation with regional brain monoamine levels. 

Psychopharmacology (Berl) 68(1):37-42. 

*Ali SF, Hasan M, Tariq M. 1979. Levels of dopamine, norepinephrine & 5-hydroxytryptamine in 

different regions of rat brain & spinal cord following chronic administration of organophosphate 

pesticide dichlorvos. Indian J Exp Biol 17(4):424-426. 

*AMUAC Chemical Corp. 1990. A 52-week chronic toxicity study on DDUP in dogs. Unpublished 

report dated August 6, 1990 submitted by AMUAC Chemical Corp. Los Angeles CA. 

*Andersen ME, Clewell HJ, III, Gargas ML, et al. 1987. Physiologically based phartnacokinetics and 

the risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87: 185-205. 

*Andersen ME, Krishnan K. 1994. Relating in vitro to in vivo exposures with physiologically-based 

tissue dosimetry and tissue response models. Current concepts and approaches on animal test 

alternatives. H. Salem, ed. U.S. Army Chemical Research Development and Engineering Center, 

Aberdeen Proving Ground, Maryland. 

*AOAC. 1990. DDVP in pesticide formulations. Infrared spectrophotometric method. Method 

1.964.04. In: Official methods of analysis of the Association of Official Analytical Chemists. K. 

Helrich, ed. 15th edition. Association of Official Analytical Chemists, Inc., Arlington, VA. 199. 

*Aquilina G, Benigni R, Bignami M. et al. 1984. Genotoxic activity of dichlorvos, trichlorfon, and 

dichloroacetaldehyde. Pestic Sci 15:439-442. 

*Askew J, Ruzicka JHA, Wheals BB. 1969. Determination of organophosphorus pesticide residues in 

river waters and effluents by gas, thin-layer, and gel chromatography. Analyst (London) 

94( 11):275-283. 

*ASTER. 1996. ASTER Ecotoxicology Profile: Phosphoric acid, 2,2-Dichloroethenyl dimethyl ester 

(Dichlorvos). Duluth, MN: U.S. EPA Environmental Research Laboratory. 

*Cited in text 
DICHLORVOS 180 

8. REFERENCES 

*ASTM. 1994. Method D5475-93. Nitrogen and Phosphorus containing pesticides in water by gas 

chromatography with a nitrogen phosphorus detector. Annual book of ASTM standards. Philadelphia, 

PA: American Society for Testing and Materials. 

*ATSDR. 1989. Decision guide for identifying substance-specific data needs related to toxicological 

profiles. Agency for Toxic Substances and Disease Registry, Division of Toxicology, Atlanta, GA. 

*ATSDR/CDC. 1990. Subcommittee report on biological indicators of organ damage. Agency for 

Toxic Substances and Disease Registry, Centers for Disease Control and Prevention, Atlanta, GA. 

*Barnabas IJ, Dean JR, Hitchen SM, et al. 1994. Selective extraction of organochlorine and 

organophosphorus pesticides using a combined solid phase extraction-supercritical fluid extraction 

approach. Anal Chim Acta 291(3):261-267. 

*Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health risk 

assessments. U.S. Environmental Protection Agency. Regul Toxicol Pharmacol 8:47 I-486. 

*Benford DJ, Price SC, Lawrence JN. 1994. Investigations of the genotoxicity and cell proliferative 

activity of dichlorvos in mouse forestomach. Toxicology 92: 1203- 1205. 

*Berteau PE, Knaak JB, Mengle DC, et al. 1989. Insecticide Absorption from Indoor Surfaces: 

Hazard Assessment and Regulatory Requirements. In: Biological Monitoring for Pesticide Exposure: 

Measurement, Estimation and Risk Assessment, R.G.M. Wang, ed. American Chemical Society, 

Washington, DC. 3 15-326. 

*Blair D, Dix KM, Hunt PF, et al. 1976. Dichlorvos -- a 2-year inhalation carcinogenesis study in 

rats. Arch Toxicol 35(4):28 l-294. 

*Blair D, Hoadley C, Hutson DH. 1975. The distribution of dichlorvos in the tissues of mammals 

after its inhalation or intravenous administration. J Toxicol Appl Pharmacol 31(2):243-253. 

*Bowman BT, Sans WW. 1983. Determination of octanol-water partitioning coefficients KOW61 

organophosphorus and carbamate insecticides and their relationship to respective water solubility (S) 

values. J Environ Sci Health [B] 13:667-633. 

*Bayer AC, Brown LJ, Slornka MB, et al. 1977. Inhibition of human plasma cholinesterase by 

ingested dichlorvos: effect of formulation vehicle. J Toxicol Appl Pharmacol 41(2):389-394. 

*Braun R, Schoeneich J, Weissflog L, et al. 1982. Activity of organophosphorus insecticides in 

bacterial tests for mutagenicity and DNA repair. Direct alkylation vs. Metabolic activation and 

breakdown. 1. Butonate, vinyl butonate, trichlorfon, dichlorvos, demethyl dichlorvos, and demethyl 

vinyl butonate. Chem-Biol Interact 39(3):339-350. 

*Brouwer DH, Ravensberg JC, De Kort WL, et al. 1994. A personal sampler for inhalable 

mixed-phase aerosols: Modification to an existing sampler and validation test with three pesticides. 

Chemosphere 28(6):1135-l 146. 

*Bryant RJ, Minett W. 1978. A gas-chromatographic method for the determination of dichlorvos in 

air. Pestic Sci 9(6):525-528. 
DICHLORVOS 181 

8. REFERENCES 

*Carere A, Cardamone G, Ortali V, et al. 1976. Mutational studies with some pesticides in 

Streptomyces coelicolor and Salmonella typhimurium. Mutat Res 38(2):136. 

*Carere A, Ortali VA, Cardamone G, et al. 1978. Microbiological mutagenicity studies of pesticides 

in vitro. Mutat Res 57(3):277-286. 

*Caroldi S, Lotti M. 1981. Delayed neurotoxicity caused by a single massive dose of dichlorvos to 

adult hens. Toxicol Letters 9: 157- 159. 

*Casale G P, Cohen S D, Dicapua R A. 1983. The effects of organophosphate induced cholinergic 

stimulation on the antibody response to sheep erythrocytes in inbred Mice. J Toxicol Appl Pharmacol 

68(2): 198-205. 

*Casale GP, Vennerstrom JL, Bavari S, et al. 1993. Inhibition of interleukin 2 driven proliferation of 

mouse CTLL2 cells, by selected carbamate and organophosphate insecticides and congeners of 

carbaryl. Immunopharmacol Immunotoxicol 15(2-3): 199-215. 

*Casida JE, McBride L, Neidermeier RP. 1962. Metabolism of 2,2-dichlorovinyl dimethyl phosphate 

in relation to residues in milk and mammalian tissue. J Agric Food Chem 10:370-377. 

*CELDs. 1994. Computer-assisted Environmental Legislative Database. University of Illinois at 

Urbana. 

*Given M, Brown CB, Morin RJ. 1977. Effects of organophosphate insecticides on adrenal 

cholesterylester and steroid metabolism. Biochem Pharmacol 26(20):1901-1907. 

*Clewell HJ III, Andersen ME. 1985. Risk assessment extrapolations using physiologically-based 

pharmacokinetic modeling. Toxicol Ind Health 1: 111-131. 

*Coppock RW, Mostrom MS, Khan AA. 1984. A review of nonpesticide phosphate ester-induced 

neurotoxicity in cattle. Vet Human Toxicol 37(6):576-579. 

*Cremlyn. 1978. Pesticides-Preparation and mode of Action. J. Wiley and Sons, LTD. 72 

*Crisp S, Tarrant KR. 1971. The determination of residues of dichlorvos and malathion in wheat 

grain by gas-liquid chromatography. Analyst 96( 14 1):3 10-3 13. 

*Cusack R, Johnson G. 1990. A study of dichlorvos (Nuvan; 2,2-dichloroethenyl dimethyl 

phosphate), a therapeutic agent for the treatment of salmonids infected with sea lice (Lepeophtheirus 

salmonis). Aquaculture 90:101-l 12. 

*Das YT, Taskar PK, Brown HD, et al. 1983. Exposure of professional pest control operator to 

dichlorvos (DDVP) and residue on house structures. Toxicol Lett 17(1-2):95-99. 

*Dean BJ, Blair D. 1976. Dominant lethal assay in female mice after oral dosing with dichlorvos or 

exposure to atmospheres containing dichlorvos. Mutat Res 40( 1):67-72. 

*Dean BJ, Thorpe E. 1972. Studies with dichlorvos vapor in dominant lethal mutation tests on mice. 

Arch Toxicol 30( 1):5 l-59. 
DICHLORVOS 182 

8. REFERENCES 

*Deer HM, Beck ED, Roe AH. 1993. Respiratory Exposure of Museum Personnel to Dichlorvos
 

Insecticide. Vet Hum Toxicol 35(3):226-228.
 

*Degraeve N, Chollet MC, Moutschen J, et al. 1972. Mutagenicity and interaction of chemicals in
 

human gastric juice. Mut Res 97:179.
 

*Degraeve N, Chollet MC, Moutschen J, et al. 1982. Genetic and cytogenetic effects of chronic
 

treatments with organophosphorus insecticides. Mutat. Res. 97:179-180.
 

*Desi I, Varga L, Farkas I. 1978. Studies on the immunosuppressive effect of organochlorine and
 

organophosphoric pesticides in subacute experiments. J Hyg Epidemiol Microbial Immunol 22( 1):
 

115-122.
 

*Di Corcia A, Samperi R, Marcomini A, et al. 1993. Graphitized carbon black extraction cartridges
 

for monitoring polar pesticides in water. Anal Chem 65(7):907-912.
 

*Dieter MP, Jameson CW, French JE, et al. 1989. Development and validation of a cellular
 

transplant model for leukemia in Fischer rats: a short-term assay for potential anti-leukemic chemicals.
 

Leuk Res 13(9):841-849.
 

*Domine D, Devilliers J, Chastrette M, et al. 1992. Multivariate structure-property relationships
 

(MSPR) of pesticides. J Pestic Sci 35:73-82.
 

*DOT. 1989. Department of Transportation. Code of Federal Regulations. 40 CFR 302.4.
 

*Durham, WF, Gaines TB, Hayes WJ. 1956. Paralytic and related effects of certain organic
 

phosphorus compounds. Arch Ind Health 13:326-330.
 

*Durham WF, Gaines TB, McCauley RH, et al. 1957. Studies on the toxicity of
 

O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP). AMA Arch Ind Health 15:340-349.
 

*Dzwonkowska A, Hubner H. 1986. Induction of chromosomal aberrations in the Syrian hamster by
 

insecticides tested in vivo. Arch Toxicol 58(3):152-156.
 

*Ecobichon DJ. 1991. Toxic effects of pesticides. In: Amdur MO, Doull J, Klaassen DC, eds.
 

Casarett and Doull’s Toxicology: The basic science of poisons, 4th ed. New York, NY: McGraw-Hill,
 

Inc. 565-622.
 

*Ehrich M, Jortner BS, Padilla S. 1995. Comparison of the relative inhibition of acetylcholinesterase
 

and neuropathy target esterase in rats and hens given cholinesterase inhibitors. Fund Appl Toxicol
 

24(1):94-101.
 

*Eisenreich SJ, Looney BB, Thornton JD. 198 1. Airborne organic contaminants in the great lakes
 

ecosystem. Environmental Science & Technology. 30-38.
 

*Elgar KE, Steer BD. 1972. Dichlorvos Concentrations in the Air of Houses Arising from the Use of
 

Dichlorvos PVC Strips. Pestic Sci 3:591-600.
 
DICHLORVOS 183 

8. REFERENCES 

*Ellinger C. 1985. Enzyme activities after in vitro and in vivo application of dichlorvos. Biomed
 

Biochim Acta 44(2):3 1 l-3 16.
 

*Ellman GL, Courtney KD, Andres V, et al. 1961. A new and rapid calorimetric determination of
 

acetylcholinesterase activity. Biochem Pharmacol 7:88-95.
 

*EPA. 1976. Investigation of Selected Potential Environmental Contaminants. Haloalkyl Phosphates. 

Environmental Protection Agency, Springfield, VA. NTIS No. PB257-910. 55-56. 

*EPA. 1978. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 116.4. 

*EPA. 1983. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 122 

App. D. 

*EPA. 1984. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 125 

Instructions Form 2c. 

*EPA. 1986. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 117.3.
 

*EPA. 1987a. Guidance for the registration of pesticide products containing DDVP as the active
 

ingredient. Office of pesticides and toxic substances, U.S. Environmental Protection Agency
 

(540/RE-88-016).
 

*EPA. 1987b. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 355
 

App. A.
 

*EPA. 1988a. Dichlorvos: Initiation of Special Review. Federal Register 53:5542-5549 [EPA Notice
 

OPP-30000/56; FRL-3332-71.
 

*EPA. 1988b. Dichlorvos: Notice of initiation of special review. U.S. Environmental Protection 

Agency.Federal Register. Part IV, 53:5542-5549. 

*EPA. 1988~. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 372.65. 

*EPA. 1988d. Method TOlO. Compendium of methods for the determination of toxic organic 

compounds in ambient air. Quality Assurance Division. Environmental Monitoring Systems 

Laboratory Office of Research and Development. U. S. Environmental Protection Agency. Research 

Triangle Park, North Carolina. 

*EPA. 1989. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 302.4. 

*EPA. 1990a. Interim methods for development of inhalation reference doses. U.S. Environmental 

Protection Agency. EPA-600/8-90/066A. 

*EPA. 1990b. pesticide fact handbook, Vol 2. U.S. Environmental protection Agency. Noyes Data 

Corporation. 203-212.
 

*EPA. 1991a. Dichlorvos: Revocation of tolerance and food additive regulations: proposed rule.
 

U.S. Environmental Protection Agency. Federal Register. 56 FR 5788-5789. 
DICHLORVOS 184 

8. REFERENCES 

*EPA. 1991b. Method 507. Determination of nitrogen- and phosphorus-containing pesticides in 

water by gas chromatography with a nitrogen-phosphorus detector. Revision 2.0. In: Methods for the 

determination of organic compounds in drinking water. Environmental Monitoring Systems 

Laboratory, U.S. Environmental Protection Agency, Cincinnati, OH. 

*EPA. 1992a. Method 622. The determination of organophosphorus pesticides in municipal and 

industrial wastewater. In: Methods for the determination of nonconventional pesticides in municipal 

and industrial wastewater. EPA 821 RR-92-002. Office of Water, U.S. Environmental Protection 

Agency, Washington DC. 

*EPA. 1992b. Method 8141A. Organophosphorus compounds by gas chromatography: capillary 

column technique. In: Test methods for evaluating solid waste. Vol lB, Laboratory manual, 

Physical/chemical methods. SW846. U.S. Environmental Protection Agency, Office of Solid Waste 

and Emergency Response, Washington DC, 4th ed. 

*EPA. 1993a. Cancellation of Pesticides for Non-Payment of Registration Maintenance Fees; Notice. 

U.S. Environmental Protection Agency. Federal Register. 58 FR 44828. 

*EPA. 1993b. Dichlorvos; Revocation of Food Additive Tolerance; Final Rule. U.S. Environmental 

Protection Agency. Federal Register. 58 FR 59663. 

*EPA. 1993~. U.S. Environmental Protection Agency. Federal Register. 59 FR 54836. 

*EPA. 1994a. Dichlorvos; Stay of Effective Date for order revoking Food Additive Regulation; Final 

Rule Stay of Effective Date. U.S. Environmental Protection Agency. Federal Register. 59 FR 11556. 

*EPA. 1994b. U.S. Environmental Protection Agency. Federal Register. 59 FR 15504. 

*EPA. 1995a. Toxic chemical release inventory reporting form R and instructions. U. S. 

Environmental Protection Agency. 745-K-95-05 1. 

*EPA. 1995b. U. S. Environmental Protection Agency. Federal Register. 60 FR 19580. April 19, 

1995. 

*EPA. 1995c. U. S. Environmental Protection Agency. Federal Register. 60 FR 50338. September 

28, 1995. 

*EPA PIN. 1994. Pesticide Monitoring Information (PMI) Facility: Project Summary of the EPA 

National Pesticide Survey of Drinking Water Wells. Washington, DC: EPA OPP Pesticide 

Information Network (PIN) On-line BBS. 

*Epstein SS, Arnold E, Andrea J, et al. 1972. Detection of chemical mutagens by the dominant lethal 

assay in the mouse. Toxicol Appl Pharmacol 23:288-325. 

*Emey DR. 1995. Determination of organophosphorus pesticides in whole-chocolate-skim-milk and 

infant formula using solid-phase extraction with capillary gas chromatography-flame photometric 

detection. HRC Journal of High Resolution Chromatography 18( 1):59-62. 
DICHLORVOS 185 

8. REFERENCES 

*Farm Chemical Handbook. 1984. Farm Chemical Handbook: Pesticide Dictionary. Meister 

Publishing Company, Willoughby, OH. C70-C71. 

*Farm Chemical Handbook. 1994. Farm Chemical handbook: pesticide dictionary. Meister 

Publishing Company, Willoughby, OH. cl 11. 

*FASE. 1996. Pesticide exports from U. S. ports, 1992-1994. Foundation for Advancement in 

Science and Education. 

*Faust SD, Suffet IH. 1966. Recovery, separation and identification of organic pesticides from 

natural and potable waters. Residues Reviews 45-l 16. 

*FDA. 1988. Food and Drug Administration Pesticide Program: Residue in Foods-1987. J Assoc Off 

Anal Chem Int 71(6):A156-A174. 

*FDA. 1989. Food and Drug Administration Pesticide Program: Residue in foods-1988. J Assoc Off 

Anal Chem Int 72(5):133-152A. 

*FDA. 1990. Food and Drug Administration Pesticide Program: Residue in foods-1989. J Assoc Off 

Anal Chem Int 73(5):127A-146A. 

*FDA. 1991. Food and Drug Administration Pesticide Program: Residue Monitoring 1990. J Assoc 

Off Anal Chem Int 74(5):A121-A140. 

*FDA. 1992. Food and Drug Administration Pesticide Program: Residue Monitoring 1991. J Assoc 

Off Anal Chem Int 75(5):A135-A157. 

*FDA. 1993. Food and Drug Administration Pesticide Program: Residue Monitoring 1992. J Assoc 

Off Anal Chem Int 76(5):A127-A148. 

*FDA. 1994a. Dichlorvos. Method 302. In: Pesticide analytical manual. Vol. 1: Multiresidues 

methods, 3rd ed. Food and Drug Administration, Public Health Service, U.S. Department of Health 

and Human Services. 

*FDA. 1994b. Method 304. In: Pesticide analytical manual. Vol. 1: Multiresidues methods, 3rd ed. 

Food and Drug Administration, Public Health Service, U.S. Department of Health and Human 

Services. 

*FDA. 1994c Residue monitoring, 1993 (8th annual FDA pesticide residue monitoring program 

report). Journal of AOAC International 77(5): 163A-185A. 

*FDA. 1995. Food and Drug Administration Pesticide Program: Pesticide residue mbnitoring 

program. J Assoc Off Anal Chem Int 73(5): 127A-146A. 

*Fedrip. 1994. Federal Research In Progress. November 1994. 

*Fedrip. 1996. Federal Research In Progress. May 1996. 
DICHLORVOS 186 

8. REFERENCES 

*Fitzgerald BB, Costa LG. 1993. Modulation of muscarinic receptors and acetylcholinesterase 

activity in lymphocytes and in brain areas following repeated organophosphate exposure in rats. Fund 

Appl Toxicol 20:210-216. 

*Francis BM, Metcalf RL, Hansen LG. 1985. Toxicity of organophosphorus esters to laying hens 

after oral and dermal administration. J Environ Sci Health [B] 20(1):73-95. 

*Gaines THB, Hayes WJ, Jr., Linder RE. 1966. liver metabolism of anticholinesterase compounds in 

live rats: relation to toxicity. Nature (London) 2098889. 

*Gajewski D, Katkiewicz M. 198 1. Activity of certain enzymes and histomorphological changes in 

subacute intoxication of rats with selected organophosphates. Acta Physiol Pol 32(5):507-520. 

*Gallo MA, Lawryk NJ. 1991. Organic phosphorous pesticides In: Hayes WJ, Laws ER eds, 

Handbook of Pesticide Toxicology 2:990-l 001. 

*Garcia MA, Femandez MI, Melgar JM. 1995. Contamination of honey with organophosphorus 

pesticides. Bulletin of Environmental Contamination and Toxicology 54(6):825-832. 

*Gelardi RC, Mountford MK. 1993. Infant Formulas: Evidence of the Absence of Pesticide Residues. 

Reg Toxicol Pharrnacol 17:181-192. 

*Gianessi LP. 1986. A national Pesticide Usage Data Base. Renewable Resources Division, 

Resources for the future, 1616 P Street NW, Washington, DC, 20036. 

*Goh KS, Edmiston S, Maddy KT, et al. 1986. Dissipation of Dislodgeable Foliar Residue for 

Chlorpyrifos and Dichlorvos Treated Lawn: Implications for Safe Reentry. Bull Environ Contam 

Toxicol 37:33-40. 

*Gold RE, Holcslaw T. 1985. Dermal and Respiratory Exposure of Applicators and Residents to 

Dichlorvos-Treated Residences. In: Dermal Exposure Related to Pesticide Use: Discussion of Risk 

Assessment, Honeycutt RC, Zweig G, Ragsdale NN, eds. American Chemical Society, Washington, 

DC. 253-264. 

*Gore RC, Hannah RW, Pattacini SC, et al. 1971. Pesticide Residues: Infrared and Ultraviolet 

Spectra of Seventy-six Pesticides. J Assoc Off Anal Chem 54(5): 1040-1081. 

*Green MH, Medcalf AS, Arlett CF, et al. 1974. DNA strand breakage caused by dichlorvos, methyl 

methanesulphoneate and iodoacetamide in escherichia coli and cultured Chinese hamster cells. Muta 

Res 24(3):365-378. 

*Gupta AK, Singh J. 1974. Dichlorvos (DDVP) induced breaks in the salivary gland-chromosomes 

of Drosophila melanogaster. Cut-r Sci 43(20):661-662. 

*Haley TJ, Farmer JH, Harmon JR, et al. 1975. Estimation of the LDl and extrapolation of the 

LDO. 1 for five organophosphate pesticides. Arch Toxicol 34(2): 103- 109. 

*Hanna PJ, Dyer KF. 1975. Mutagenicity of organophosphorus compounds in bacteria and 

Drosophila. Mutat Res 28:405-420. 
DICHLORVOS 187 

8. REFERENCES 

*Haraguchi K. Kitamura E, Yamshita T, et al. 1995. Simultaneous determination of trace pesticides 

in urban precipitation. Atmospheric Environment 29(2):247-253. 

*Hartley IC, Hart JP. 1994. Amperometric measurement of organophosphate pesticides using a 

screen-printed disposable sensor and biosensor based on cobalt phthalocyanine. Analytical 

Proceedings, 31(11):333-337. 

*Hatch FF, Anderson TM, Lubet RA, et al. 1986. Chemical enhancement of SA7 virus 

transformation of hamster embryo cells: Evaluation by interlaboratory testing of diverse chemicals. 

Environ Mutagen 8(4):5 15-53 1. 

*Hayes WJ, Jr. 1963. Clinical handbook on economic poisons: emergency information for treating 

poisoning. Public Health Service publication no. 476. Communicable Diseases Center, Public Health 

Service, US Department of Health, Education, and Welfare. Atlanta, GA. 

*Hayes WJ, Jr. 1982. Organic phosphorus pesticides. In: Pesticides Studied in Man. Williams & 

Wilkins, Baltimore, MD. 343-351. 

*HazDat. 1995. Hazardous substances Database. Agency for Toxic Substance and Disease Registry 

(ATSDR), Atlanta, GA. 

*HazDat. 1996. Hazardous substances Database. Agency for Toxic Substance and Disease Registry 

(ATSDR), Atlanta, GA. 

*Heuser SG, Scudamore KA. 1966. A rapid method for sampling dichlorvos vapor in air. Chem Ind 

(London) 50:2093-2094. 

*Hoey T, Horsberg TE, Wichstrom R. 1991. Inhibition of acetylcholinesterase in rainbow trout 

following dichlorvos treatment at different water oxygen levels. Aquaculture 95133-40. 

*Holland PT. 1977. Routine methods for analysis of organophosphorus and carbamate insecticides in 

soil and ryegrass. Pestic Sci 8(4):354-358. 

*Holland PT, McNaughton DE, Malcolm CP. 1994. Multiresidue analysis of pesticides in wines by 

solid-phase extraction. J Assoc Off Anal Chem Int 77(1):79-86. 

*Holstege DM, Scharberg DL, Richardson ER, et al. 199 1. Multiresidue screen for organophosphorus 

insecticides using gel permeation chromatography - silica gel cleanup. J Assoc Off Anal Chem 

74(2):394-399. 

*Horsberg TE, Hoey T. 1990. Residues of dichlorvos in Atlantic Salmon (Salmon salar) after 

delousing. J Agric Food Chem 38:1403-1406. 

*Howard PH. 1991. Handbook of Environmental Fate and Exposure Data for Organic Chemicals. 

Vol. III. Lewis Publishers, Chelsea, MI. 251-258. 

*Howden CW, Bimie CC, Brodie MJ. 1989. Drug Metabolism in liver disease. Pharmacol Ther 

40:439-474. 
DICHLORVOS 188 

8. REFERENCES 

*HSDB. 1994. Hazardous Substance Data Bank. National Library of Medicine, National Toxicology 

Program. Bethesda MD. November 1994. HSN 319. 

HSDB. 1996. Hazardous Substance Data Bank. National Library of Medicine, National Toxicology 

Program. Bethesda MD. May 1996. 

*Hsu JP, Wheeler HG Jr., Camann DE, et al. 1988. Analytical methods for detection of 

nonoccupational exposure to pesticides. J Chromatogr Sci 26(4): 18 l- 189. 

*Huff RA, Corcoran JJ, Anderson JK, et al. 1994. Chlorpyrifos oxon binds directly to muscarinic 

receptors and inhibits CAMP accumulation in rat striatum. J Pharmacol Exp Ther 269:329-335. 

*Hutson DH, Hoadley EC. 1972a. The comparative metabolism of [ 14C-vinyl] dichlorvos in animals 

and man. Arch Toxicol 30(1):9-l8. 

*Hutson DH, Hoadley EC. 1972b. The metabolism of [14 C-methyl] dichlorvos in the rat and the 

mouse. Xenobiotica 2: 107- 116. 

*Hutson DH, Hoadley EC, Pickering BA. 1971. The metabolic fate of [vinyl-I-14C] dichlorvos in 

the rat after oral and inhalation exposure. Xenobiotica 1(6):593-611. 

*IARC. 1979. IARC monographs on the evaluation of carcinogenic risk to humans. Occupational 

exposure in insecticide application, and some pesticides, vol. 20. International Agency for Research 

on Cancer, Lyon, France. 

*IARC. 1991. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Occupational 

Exposures in Insecticide Application, and Some Pesticides; Dichlorvos, Vol. 53. International Agency 

for Research on Cancer, UN World Health Organization, Geneva, Switzerland. 267-307. 

*Ikeda T, Kojima T, Yoshida M, et al. 1990. Pretreatment of rats with an organophosphorus 

insecticide, chlorfenvinphos, protects against subsequent challenge with the same compound. Fundam 

Appl Toxicol 14(3):560-567. 

*Imato T, Ishibashi N. 1995. Potentiometric butyrylcholine sensor for organophosphate pesticides. 

Biosensors & Bioelectronics 10(5):435-441. 

*IRIS. 1995. Integrated Risk Information System. U.S. Environmental Protection Agency, 

Environmental Criteria and Assessment Office, Cincinnati, OH. 

*IRIS. 1996. Integrated Risk Information System. U.S. Environmental Protection Agency, 

Environmental Criteria and Assessment Office, Cincinnati, OH. 

*IRPTC. 1985. Treatment and disposal methods for waste chemicals (IRPTC file). Data profile 

series no. 5. Geneva, Switzerland: United Nations Environmental Programme. 

*Ivey MC, Clabom HV. 1969. GLC (gas-liquid-chromatographic) determination of dichlorvos in 

milk, eggs, and various body tissues of cattle and chickens. J Assoc Off Anal Chem 52(6): 1248- 1251. 
DICHLORVOS 189 

8. REFERENCES 

*Ivnitskii DM, Rishpon J. 1994. A potentiometric biosensor for pesticides based on the thiocholine 

hexacyanoferrate (iii) reaction. Biosensors & Bioelectronics 9(8):569-576. 

*Jayasuriya VU, De S, Ratnayake WE. 1973. Screening of some pesticides on Drosophila 

melanogaster for toxic and genetic effects. Drosophila Inf Serv 50: 184-186. 

*Johnson MK. 1978. The anomalous behavior of dimethyl phosphates in the biochemical test for 

delayed neurotoxicity. Arch Toxicol 41: 107-l 10. 

*Johnson MK. 198 1. Delayed neurotoxicity: Do trichlorfon and/or dichlorvos cause delayed 

neuropathy in man or test animals ? Acta Pharmacol Toxicol 49:87-98. 

*Julka D, Pal R, Gill KD. 1992. Neurotoxicity of dichlorvos: effect on antioxidant defense system in 

the rat central nervous system. Exp Mol Path01 56(2):144-152. 

*Kadenczki L, Arpad Z, Gardi I, et al. 1992. Column extraction of residues of several pesticides 

from fruits and vegetables: A simple multiresidue analysis method. J Assoc Off Anal Chem Int. 75 

1:53-61. 

*Kadokami K, Morimoto M, Haraguchi K, et al. 1991. Multiresidue determination of trace pesticides 

in water by gas chromatography/mass spectrometry with selected ion monitoring. Anal Sci 

7(2):247-252. 

*Kan-Do Office and Pesticide Team. 1995. Accumulated pesticide and industrial chemical findings 

from a ten year study of ready-to-eat foods. J AOAC Int 78(3):614-630. 

*Kawamoto K, Urano K. 1989. Parameters for predicting fate of organochlorine pesticide in the 

environment (1) Octanol-water and air-water partition coefficients. Chemosphere 18: 1986- 1989. 

*Kawasaki S, Ueda H, Itoh H, et al. 1992. Screening of organophosphorus pesticides using liquid 

chromatography-atmospheric pressure chemical ionization mass spectrometry. J Chromatogr 

595(1-2):193-202. 

*Kelly TJ, Mukund R, Spicer CW, et al. 1994. Concentrations and transformations of hazardous air 

pollutants. Environ Sci Technol 28(8):378A-387A 

*Kenaga EE. 1980. Predicted bioconcentration factors and soil sorption coefficients of pesticides and 

other chemicals. Ecotox Environ Safety 9(4):26-38. 

*Kikuchi H, Suzuki Y, Hashimoto Y. 1981. Increase of beta glucuronidase activity in the serum of 

rats administered organophosphate and carbamate insecticides. J Toxicol Sci 6( 1):27-36. 

*Kligerman AD, Exexson GL, Wilmer JL. 1985. Induction of sister chromatid exchange (SCE) and 

cell-cycle inhibition in mouse peripheral blood B lymphocytes exposed to mutagenic carcinogens in 

vivo. Mutat Res 157:181-187. 

*Kozlowska A, Sadurska B, Szymczyk T. 1988. Effect of dichlorvos on the activity of lipoprotein 

lipase from adipose tissue, on plasma lipids and posthepatin lipolytic plasma activity in rats. Arch 

Toxicol 62(2-3):227-229. 
DICHLORVOS 190 

8. REFERENCES 

*Kramers PGN, Knaap AGAC. 1978. Absence of a mutagenic effect after feeding dichlorvos to 

larvae of Drosophila melanogaster. Mutat Res 57( 1): 103-105. 

*Krishnan K, Andersen ME. 1994. Physiologically-based pharmacokinetic modeling in toxicology. 

In: Principles and methods of toxicology. 3rd edition, Wallace Hayes, ed. Raven Press, Ltd. New 

York, NY. 

*Krishnan K, Andersen ME, Clewell HJ III, et al. 1994. Physiologically-based pharmacokinetic 

modeling of chemical mixtures. In: Toxicology of chemical mixtures, R.S.A. Yang, ed. Academic 

Press, New York, NY. 

*Kusic R, Jovanovic D, Randjelovic S, et al. 1991. HI-6 in man: efficacy of the oxime in poisoning 

by organophosphorus insecticides. Hum Exp Toxicol l0(2): 113- 118. 

*Lacorte S, Ehresmann N, Barcelo D. 1995. Stability of organophosphorus pesticides on disposable 

solid-phase extraction precolumns. Environ Sci Tech 29( 11):2834-2841. 

*Lamoreaux RF, Newland LW. 1978. The Fate of Dichlorvos in Soil. Chemoshpere 10:807-814. 

*Lartiges S, Garrigues P. 1993. Determination of organophosphorus and organonitrogen pesticides in 

water and sediments by GC-NPD and GC-MS. Analusis 21(3):157-165. 

*Lartiges SB, Garrigues PP. 1995. Degradation kinetics of organophosphorus and organonitrogen 

pesticides in different waters under various environmental conditions. Environ Sci Technol 

29: 1246- 1264. 

*Latif S, Haken JK, Wainwright S, et al. 1984. Gas chromatographic analysis of insecticidal 

preparations using carbon dioxide propellants. J Chromatogr 287:77-84. 

*Leary JS, Kenae WT, Fontenot C, et al. 1974. Safety Evaluation in the Home of Polyvinyl Chloride 

Resin Strip Containing Dichlorvos (DDVP). Arch Environ Health 29:308-314. 

*Lehotay SJ, Eller KI. 1995. Development of a method of analysis for 46 pesticides in fruits and 

vegetables by supercritical fluid extraction and gas chromatography/ion trap mass spectrometry. J 

AOAC Int 78(3):821-830. 

*Leighton BL, Cheek TG, Gross JB, et al. 1986. Succinylcholine pharmacodynamics in peripartum 

patients. Anesthesiology 64(2):202-205. 

*Leung H. 1993. Physiologically-based pharmacokinetic modeling. General and Applied Toxicology. 

Vol. I. Ballantine B, Marro T, Turner T, eds. Stockton Press, New York, NY. 153-164. 

*Lewis RG, Bond AE, Johnson DE, et al. 1988. Measurement of Atmospheric Concentrations of 

Common Household Pesticides: A Pilot Study. Environ Monit Assess 10:59-73. 

*Lieberman MT, Alexander M. 1983. Microbial and Nonenzymatic Steps in the Decomposition of 

Dichlorvos (2,2-Dichlorovinyl O,O-Dimethyl Phosphate). J Agric Food Chem 31(2):265-267. 
DICHLORVOS 191 

8. REFERENCES 

*Liu J, Suzuki O, Kumazawa T, et al. 1989. Rapid isolation with Sep-Pak Cl8 cartridges and 

wide-bore capillary gas chromatography of organophosphate pesticides. Forensic Sci Int 41( 1):67-72. 

*Lockridge O. 1990. Genetic variants of human serum cholinesterase influence metabolism of the 

muscle relaxant succinylcholine. Pharmacol Ther 47( 1):35-60. 

*Loeffler JE, De Vries DM, Young R, et al. 1971. Metabolic fate of inhaled dichlorvos in pigs. 

Toxicol Appl Pharmacol 19:378. 

*Loeffler JE, Potter JC, Scordelis SL, et al. 1976. Long term exposure of swine to a 14C dichlorvos 

atmosphere. J Agric Food Chem 24(2):367-371. 

*Lofroth G. 1970. Alkylation of DNA by dichlorvos. Radiobiology Department of the Biochemistry 

Institute University of Stockholm, Stockholm, Sweden. 

*Lopez-Avila V, Dodhiwala NS, Beckert WF. 1990. Supercritical fluid extraction and its application 

to environmental analysis. J Chromatogr Sci 28(9):468-476. 

*Lotti M, Johnson MK. 1978. Neurotoxicity of organophosphorus pesticide: Predictions can be based 

on in vitro studies with hen and human enzymes. Arch Toxicol 41:215-221. 

*Mackison FW. 1981. Occupational health guidelines for chemical hazards. U.S. Department of 

Health and Human Services, Public Health Service, Washington, DC. DHHS (NIOSH) Publ. No. 

81-123. 

*Mali BD, Garad MV, Patil VB, et al. 1995. Thin-layer chromatographic detection of dichlorvos and 

dimethoate using orcinol. J Chromatogr A 704(2):540-543. 

*Markell CG, Hagen DF, Luedtke JD. 1994. Solid phase extraction medium for wastewater 

treatment. U.S. Patent No. 5,279,742. 

*Marking LL. 1992. Evaluation of Toxicants for the Control of Carp and other Nuisance Fishes. 

Fisheries 17:6- 11. 

*Martorell D, Cespedes F, Martinez FE, et al. 1994. Amperometric determination of pesticides using 

a biosensor based on a polishable graphite-epoxy biocomposite. Analytica Chimica Acta 

290(3):343-348. 

*Maslinska D, Lewandowska I, Prokopczyk J. 1981. Effect of prolonged acetylcholinesterase 

inhibition on postnatal brain development in rabbit. I. Level of serotonin in different brain regions. 

Acta Neuropathol Suppl (Berl) 7:52-55. 

*Maslinski S, Ciurzynska G, Maslinska D. 1979. Dichlorvos intoxication and gastric secretion. Acta 

Physiol Pol 30(5-6):657-660. 

*Mathias CG. 1983. Persistent contact dermatitis from the insecticide dichlorvos. Contact Derm 

9(3):217-218. 
DICHLORVOS 192 

8. REFERENCES 

*Maxwell DM. 1992. The specificity of carboxylesterase protection against the toxicity of 

organophosphorus compounds. Toxicol Appl Pharmacol 114:306-3 12. 

*McHenery JG, Saward D, Seaton DD. 1991. Lethal and sub-lethal effects of the salmon delousing 

agent dichlorvos on the larvae of the lobster (Homarus gammarus L.) and herring (Clupea harengus 

L.). Aquaculture 98:331-347. 

*Menz M Luetkemeier, H. Sachsse K. 1974. Long-term exposure of factory workers to dichlorvos 

(DDVP) insecticide. Arch environ health 28:72-76. 

*Menzie CM. 1972. Fate of Pesticides in the Environment. Ann Rev Entomol 17:199-222. 

*Merck. 1989. Merck index: an encyclopedia of chemicals, drugs, and biologicals. 1 lth ed. 

Budavari S, ed. Merck & Co., Inc., Rahway, NJ. 

*Ministry of Agriculture, Fisheries and Food. 1977. Determination of residues of organophosphorus 

pesticides in fruits and vegetables. Analyst 102:858-868. 

*Minyard JP Jr., Roberts WE. 1991. State Findings on Pesticide Residues in Foods 1988 and 1989. J 

Assoc Off Anal Chem 74(3):438-452. 

*Miyahara M, Okada Y, Takeda H, et al. 1994. Multiresidue procedures for the determination of 

pesticides in food using capillary gas chromatographic, flame photometric, and mass spectrometric 

techniques. Journal of Agricultural and food Chemistry 42( 12):2795-2802. 

*Mohammad FK, al-Kassim NA, Abdul-Latif AR. 1989. Effect of diphenhydramine on 

organophosphorus insecticide toxicity in mice. Toxicology 58(1):91-95. 

*Moriearty PL, Thornton SL, Becker RE. 1993. Transdermal patch delivery of acetylcholinesterase 

inhibitors. Meth Find Exp Clin Pharmacol 15(6):407-412. 

*Moriya M, Kato K, Shirausu Y. 1978. Effects of cysteine and a liver metabolic activation system on 

the activities of mutagenic pesticides. Muta Res 57:259-263. 

*Moriya M, Ohta T, Watanabe K, et al. 1983. Further mutagenicity studies on pesticides in bacterial 

reversion assay systems. Mutat Res 116: 185-216. 

*Moutschen-Dahmen J, Moutschen-Dahmen M, Degraeve N. 198 1. Metrifonate and dichlorvos: 

cytogenetic investigations. Acta Pharmacol Toxicol (Copenh) 49:29-39. 

*Mueller DK. 1992. Dichlorvos Under Siege. Pest Control 60(1):44-46. 

*Nag M. 1992. Effect of organophosphate pesticides on glutaminase synthetase activity in rat brain. 

Indian J Exp Biol 30(6):543-545. 

*Nakamura Y, Sekiguchi S, Hasegawa S, et al. 1993. Reductions in Postharvest-Applied Dichlorvos, 

Chlorpyrifos-methyl, malathion, Fenitrothion, and Bromide in Rice during Storage and Cooking 

Processes. J Agric Food Chem 41(11):1910-1915. 
DICHLORVOS 193 

8. REFERENCES 

*Nakamura Y, Tonogai Y, Sekiguchi Y, et al. 1994. Multiresidue analysis of 48 pesticides in 

agricultural products by capillary gas chromatography. Journal of Agricultural and Chemistry 

42(11):2508-2518. 

*NAS/NRC. 1989. Biologic markers in reproductive toxicology. National Academy of 

Sciences/National Research Council. National Academy Press, Washington, DC. 15-35. 

*NCI. 1977. Bioassay of dichloryos for possible carcinogenicity (CAS No. 62-73-7). Carcinogenesis 

technical report series No. 10. National Cancer Institute, National Institutes of Health, Public Health 

Service, Department of Health, Education, and Welfare, Bethesda, MD. l-98. 

*Nichol AW, Angel LA. 1984. A comparative study of porphyrin accumulation in tissue cultures of 

chicken embryo hepatocytes treated with organophosphorus pesticides. Biochem Pharmacol 

33(15):2511-2515. 

*Nicholas AH, Vienne M, Van Den Berghe H. 1978. Sister chromatid exchange frequencies in 

cultured human cells exposed to an organophosphorus insecticide dichlorvos. Toxicol Lett 2:271-275. 

*Nicolau GY. 1983. Circadian rhythms of RNA, DNA and protein in the rat thyroid, adrenal and 

testis in chronic pesticide exposure. III. Effects of the insecticides (dichlorvos and trichlorphon). 

Physiologie 20(2):93-101. 

*NIOSH. 1990. NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety 

and Health, U.S. Dept. of Health and Human Services, Cincinnati, OH. 

*NIOSH. 1992. NIOSH recommendations for occupational safety and health, compendium of policy 

documents and statements. National Institute for Occupational Safety and Health, U.S. Dept. of Health 

and Human Services, Cincinnati, OH. 

*NIOSWOSHA. 198 1. Occupational Health Guidelines for Chemical Hazards. U. S. Department of 

Health and Human Services, Public Health Services, Centers for Disease Control, National Institute for 

Safety and Health Administration. Publication No. 81-123. 

*Nishio A, Uyeki EM. 1982. Nuclease sensitivity of methylated DNA as a probe for chromatin 

reconstitution by genotoxicants. Biochemical Biophysical Research Communications 107(2):485-491. 

*NOES. 1991. National Occupational Exposure Survey (198 l- 1983): Dichlorvos. National Institute 

for Occupational Safety and Health, U.S. Department of Health and Human Services, Cincinnati, OH. 

*Nordgren I. 1981. Quantitation of metrifonate and dichlorvos in blood and tissues by gas 

chromatography-mass spectrometry. Fundam Appl Toxicol 1(2):230-237. 

*Nordgren I, Bengtsson E, Holmsted B, et al. 1981. Levels of metrifonate and dichlorvos in plasma 

and erythrocytes during treatment of schistosomiasis with Bilarcil. Acta Pharmacol Toxicol Suppl. 

49(5):79-86. 

*NTP. 1989. Toxicology and carcinogenesis studies of dichlorvos in F344/N rats and B6C3Fl mice 

(gavage studies). NTP Technical Report TR 324, NIH Publication No. 89-2398. National Toxicology 
DICHLORVOS 194 

8. REFERENCES 

Program, National Institutes of Health, U. S. Department of Health and Human Services. Research 

Triangle Park, NC. 

*NTP. 1995. Printed long term technical reports and short term toxicity study reports. National 

Toxicology Program. Management Status Report. Division of Toxicology Research and Testing. 

National Institute of Environmental Health Sciences. July 7, 1995. 

*Okumura D, Melnicoe R, Jackson T, et al. 199 1. Pesticide Residues in Food Crops Analyzed by the 

California Department of Food and Agriculture in 1989. Rev Environ Contam Toxicol 118:87-151. 

*OSHA. 1974. U.S. Occupational Safety and Health Administration. Code of Federal Regulations. 29 

CFR 1910.1000. 

*OSHA. 1986. Chlorpyrifos, DDVP, diazinon, malathion, parathion. Method 62. Organic Methods 

Evaluation Branch, OSHA Analytical Laboratory, Occupational Safety and Health Administration, 

Salt Lake City, UT. 

*OSU. 1992. Ohio Livestock Manure and Wastewater Management Guide. Bulletin 604. Ohio 

Cooperative Extension Service, Ohio State University, Columbus, OH. 

*OTA. 1990. Neurotoxicology: Identifying and controlling poisons of the nervous system. Office of 

Technology Assessment, Washington, DC. OTA-BA-438. 

*Pachecka J, Grzadkowska K, Gajewski K. 1980. The activity of plasma phosphatases in rats treated 

with single doses of dichlorvos and trichlorphon. Acta Physiol Pol 31(5):555-559. 

*Pachecka J, Sulinski A, Traczykiewicz K. 1977. The effect of acute intoxication by dichlorvos and 

trichlorphon on the activities of some rat brain esterases. Neuropatol Pol 15(1):85-92. 

*Paik SG, Lee SY. 1977. Genetic effects of pesticides in the mammalian cells. I. Induction of 

micronucleus. Korean J Zoo 120: 19-28. 

*PIP-Dichlorvos. 1993. EXOTOXNET Profile for Dichlorvos. Extension Toxicology Network, 

Pesticide Information Project, Cornell University, Ithaca, NY. 

*PIP-Naled. 1994. EXOTOXNET Profile for naled. Extension Toxicology Network, Pesticide 

Information Project, Cornell University, Ithaca, NY. 

*PIP-Trichlorfon. 1993. EXOTOXNET Profile for Trichlorfon. Extension Toxicology Network, 

Pesticide Information Project, Cornell University, Ithaca, NY. 

*Potter JC, Boyer AC, Marxmiller RL, et al. 1973a. Radioisotope residues and residues of dichlorvos 

and its metabolites in pregnant sows and their progeny dosed with dichlorvos-14C or dichlorvos- 36Cl 

formulated as PVC pellets. J Agric Food Chem 21(4):734-738. 

*Potter JC, Loeffler JE, Collins RD, et al. 1973b. Carbon-14 balance and residues of dichlorvos and 

its metabolites in pigs dosed with dichlorvos-14C. J Agric Food Chem 21(2):163-166. 
DICHLORVOS 195 

8. REFERENCES 

*Rasmussen WA, Jensen JA, Stein WJ, et al. 1963. Toxicological Studies of DDVP for Disinsection 

of Aircraft. Aerospace Med 34593-600. 

*Reiner E, Plestina R. 1979. Regeneration of cholinesterase activities in humans and rats after 

inhibition by O,O-dimethyl-2,2-dichlorovinyl phosphate. J Toxicol Appl Pharmacol 49(3):451-454. 

*Reiner E, Simeon V, Skrinjaric-Spoljar M. 1980. Hydrolysis of O,O-dimethyl-2,2-dichlorovinyl 

phosphate (DDVP) by esterases in parasitic helminths, and in vertebrate plasma and erythrocytes. 

Comp Biochem Physiol 66(2):149-152. 

*Roinestad KS, Louis JB, Rosen JD. 1993. Determination of pesticides in indoor air and dust. J 

Assoc Off Anal Chem Int 76(5):1121-l 126. 

*Roes AH, Van Munsteren AJ, Nab FM, et al. 1987. Universal extraction/cleanup procedure for 

screening of pesticides by extraction with ethyl acetate and size exclusion chromatography. Anal 

Chim Acta 196:95- 102. 

*Schmidt G, Schmidt M, Nenner M, et al. 1979. Effects of dichlorvos (DDVP) inhalation on the 

activity of acetylcholinesterase in the bronchial tissue of rats. Arch Toxicol 42(3): 191-198. 

*Schultz DR, Marxmiller RL, Koos BA. 197 1. Residue determination of dichlorvos and related 

metabolites in animal tissue and fluids. J Agric Food Chem 19(6):1238-1243. 

*Schwetz BA, Ioset HD, Leong BK, et al. 1979. Teratogenic potential of dichlorvos given by 

inhalation and gavage to mice and rabbits. Teratology 20 (3):383-387. 

*Segerback D, Ehrenberg L. 1981. Alkylating properties of dichlorvos (DDVP). Acta Pharmacol 

Toxicol 49:56-66. 

*Shellenberger TE, Newell GW, Okamoto SS, et al. 1965. Response of rabbit whole blood 

cholinesterase in vivo after continuous intravenous infusion and percutaneous application of dimethyl 

organophosphate inhibitors. Biochem Pharm 14:943-952. 

*Shevchuk IA, Dubchenko YG, Grudneva GE. 1987. Solvent extraction isolation and separate 

determination of glyphosate and dichlorvos in aqueous solutions. J Anal Chem USSR 42(2):267-270. 

*Shirasu Y, Moriya M, Kato K, et al. 1976. Mutagenicity screening of pesticides in the microbial 

system. Mutat Res 40( 1): 19-30. 

*Siers DG, Schooley MA, Brown LJ, et al. 1977. Management program for improving sow and gilt 

performance by feeding dichlorvos. Am J Vet Res 38( 12): 1997- 1999. 

*Sittig M. 1980. Pesticide Manufacturing and Toxic Materials Control Encyclopedia. Noyes Data 

Corporation, Park Ridge, NJ. 293-294. 

*Sittig M. 1985. Handbook of Toxic and Hazardous Chemicals and Carcinogen, Second Edition. 

Noyes Data Corporation, Park Ridge, NJ. 334-335. 
DICHLORVOS 196 

8. REFERENCES 

*Sittig M. 1994. World-wide limits for toxic and hazardous chemicals in air, water and soil. Noyes 

Data Corporation, Park Ridge, NJ. 

*Smart NA. 1977. Determination of residues of organophosphorus pesticides in fruits and vegetables. 

Analyst (LONDON) 202(1):858-868. 

*Snow DH, Watson AD. 1973. The acute toxicity of dichlorvos in the dog. 1. Clinical observations 

and clinical pathology. Aust Vet J 49(3):113-l 19. 

*Snyder JL, Grob RL, Mcnally ME, et al. 1992. Comparison of supercritical fluid extraction with 

classical sonication and soxhlet extractions for selected pesticides. Anal Chem 64( 17): 1940-1946. 

*Sobels FH, Todd NK. 1979. Absence of a mutagenic effect of dichlorvos in Drosophila 

melanogaster. Mutat Res 67(1):89-92. 

*SRC. 1994. Syracuse Research Center. Henry’s Law Program (HENRYWIN) version 2.50, serial 

H0142. Chemical hazard assessment division, Environmental Chemistry Center, Syracuse, NY. 

*SRC. 1995. Syracuse Research Center. Atmospheric Oxidation Program(AOPWIN) version 1.65, 

serial 0156. Chemical Hazard Assessment Division, Environmental Chemistry Center, Syracuse, NY. 

*SRI. 1994. Stanford research institute. 1994 Directory of chemical producers, United states of 

America. SRI international, Menlo park, CA. 103. 

*Stanton HC, Albert JR, Mersmann HJ. 1979. Studies on the pharmacology and safety of dichlorvos 

in pigs and pregnant sows. Am J Vet Res 40(3):315-320. 

*Sunshine. 1969. Handbook of Analytical Toxicology. 

*Swarm RL, Laskowski DA, McCall PJ, et al. 1983. A rapid method for the estimation of the 

environmental parameters 0ctanoVwater partition coefficient, soil sorption constant, water to air ratio, 

and water solubility. Bow Chemical Company, Springer-Veriag New York Inc. 

*Takahashi H, Kato A, Yamashita E, et al. 1987. Potentiations of N-methylcarbamate toxicities by 

organophosphorus insecticides in male mice. Fundam Appl Toxicol 8(2):139-146. 

*Takamiya K. 1994. Monitoring of urinary alkyl phosphates in pest control operators exposed to 

various organophosphorus Insecticides. Bull Environ Contam Toxicol 52(2): 190- 195. 

*Taylor P, Li Y, Camp S, et al. 1993. Structure and regulation of expression of the 

acetylcholinesterase gene. Chem Biol Interactions 87: 199-207 

*Teichert K, Szymczyk T, Consolo S, et al. 1976. Effect of acute and chronic treatment with 

dichlorvos on rat brain cholinergic parameters. J Toxicol Appl Pharmacol 35(1):77-81. 

*Tewari SN, Harpalani SP. 1977. Determination of DDVP insecticide (dichlorvos) in biological 

fluids using TLC and calorimetry. J Indian Acad Forensic Sci 16(2):14-19. 
DICHLORVOS 197 

8. REFERENCES 

*Tewari SN, Harpalani SP, Shatma VK. 1974. Toxicological analysis of autopsy tissues in cases of 

suicide by Flit insecticide. Proc Nat1 Acad Sci India, Sect. A 44 (Pt. 3):206-210. 

*Tezuka H, Ando N, Suzuki R, et al. 1980. Sister chromatid exchanges and chromosomal aberrations 

in cultured Chinese hamster cells treated with pesticide positive in microbial reversion assays. Muta 

Res 78(2):177-191. 

*The Agrochemicals Handbook. 1991. Dichlorvos. Royal Society of Chemistry Information services. 

Thomas Graham House Science Park, Milton Rd. 

*Thier HP, Zeumer H. 1987. Manual of pesticide residue analysis, VOL. 1. H.P. Thier and H. 

Zeumer, eds. VCH Publishers, INC., New York, NY. 

*Thorpe E, Wilson AB, Dix KM, et al. 1972. Teratological studies with dichlorvos vapor in rabbits 

and rats. Arch Toxicol 30(1):29-38. 

*Toxlist. 1995. EPA proposes to cancel most uses of pesticide dichlorvos and restrict retained uses. 

Fax Correspondence. 

*Traverse R, Moretto A, Lotti M. 1989. Human serum "A"-esterases. Hydrolysis of 

O,O-dimethyl-2,2-dichlorovinyl phosphate. Biochem Pharmacol 38(4):671-676. 

*TRI92. 1994. Toxic chemical release inventory. Office of toxic Substances, U.S. Environmental 

Protection Agency, Washington, DC. 

*TRI93. 1995. Toxics Release Inventory 1992. Office of Toxic Substances, U.S. Environmental 

Protection Agency, Washington, DC. 

*Tully 0, Monissey D. 1989. Concentrations of Dichlorvos in Be&each Bui Bay, Ireland. Mar 

Pollut Bull 20(4): 190-191. 

*Ueda A, Aoyama K, Manda F, et al. 1994. Delayed-type allergenicity of triforine (saprol (R) ) 

Contact Dermatitis 31 (3): 140-145. 

*UN. 1985. Treatment and Disposal Methods for Waste Chemicals. Data Profile Series No. 5. 

International Register of Potentially Toxic Chemicals, United Nations Environment Programme, 

Geneva, Switzerland. 

*Unni LK, Hannant ME, Becker RE. 1992. High-performance liquid-chromatographic method using 

ultra-violet detection for measuring metriphonate and dichlorvos levels in human plasma. J 

Chromatogr Biomed Appl (111):99-103. 

*Volpe LS, Biagioni TM, Marquis JK. 1985. In vitro modulation of bovine caudate muscarinic 

receptor number by organophosphates and carbamates. J Toxicol Appl Pharmacol 78(2):226-234. 

*Wagstaff DJ, Winston FB. 1980. Infrared photographic measurement of pupillary effects of 

dichlorvos in Beagles. Am J Vet Res 41(6):958-959. 
DICHLORVOS 198 

8. REFERENCES 

*Wang WK, Huang SD. 1994. Determination of organophosphorus pesticides in water using Cl8 or 

Florisil Sep-Pak cartridge and gas chromatography with flame-photometric detection. J Chin Chem 

Sot (Taipei) 41(1):109-113. 

*Whitmore RW, Immerman FW, Camann DE, et al. 1994. Non-Occupational exposures to pesticides 

for residents of two U. S. cites. Arch Environ Contam Toxicol 26:45-59. 

*WHO. 1985. Specifications for pesticides used in public health insecticides, molluscicides, 

repellents, methods. 6th Edition. World Health Organization, Geneva, Switzerland. 

*WHO. 1989. Dichlorvos. Environmental Health Criteria #79. World Health Organization, Geneva, 

Switzerland. 

*WHO. 1992. Trichlorfon. Environmental Health Criteria #132. World Health Organization, Geneva, 

Switzerland. 

*Witter RF, Gaines TB, Short JG, et al. 1961. Studies on the safety of DDVP for the disinsection of 

commercial aircraft. Bull World Health Org 24:635-642. 

*Wooder MF, Wright AS, King LJ. 1977. In vivo alkylation studies with dichlorvos at practical use 

concentrations. Chem Biol Interact 19( 1):25-46. 

*Worthing CR. 1983. The pesticide manual: A world compendium. 7th ed. British Crop Protection 

Council. 

*Wright AS, Hutson DH, Wooder MF. 1979. The chemical and biochemical reactivity of dichlorvos. 

Arch Toxicol 42(1):1-18. 

*Wright CG, Leidy RB. 1980. Insecticide Residues in the Air of Buildings and Pest Control 

Buildings. Bull Environ Contam Toxicol 24:582-589. 

*Wyrobek AJ, Bruce WR. 1975. Chemical induction of sperm abnormalities in mice. Proc Natl 

Acad Sci USA 72( 11):4425-4429. 

*Yamano T, Morita S. 1992. Hepatotoxicity of trichlorfon and dichlorvos in isolated rat hepatocytes. 

Toxicology 76( 1):69-77. 

*Yamashita S, Miyajima T, Takino A, et al. 1991. Analysis for pesticides in natural water by 

capillary GC and GC/MS. Anal Sci 7(Su):1165-1166. 

*Yess NJ, Houston MG, Gunderson EL. 1991a. Food and Drug Administration Pesticide Residue 

Monitoring of Foods: 1978-1982. J Assoc Off Anal Chem 74(2):265-272. 

*Yess NJ, Houston MG, Gunderson EL. 1991b. Food and Drug Administration Pesticide Residue 

Monitoring of Foods: 1983-1986. J Off Anal Chem 74(2):273-280. 

*Zegers BN, Hogenboom AC, Dekkers SEG, et al. 1994. Packed capillary supercritical fluid 

chromatography of organophosphorus pesticides: Selective detection and applications. J Microcolumn. 

55-62. 
DICHLORVOS 199 

9. GLOSSARY
 

Acute Exposure-Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption Coefficient (Koc)-The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)-The amount of a chemical adsorbed by a sediment or soil (i.e., the solid 

phase) divided by the amount of chemical in the solution phase, which is in equilibrium with the solid 

phase, at a fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per 

gram of soil or sediment. 

Bioconcentration Factor (BCF)-The quotient of the concentration of a chemical in aquatic 

organisms at a specific time or during a discrete time period of exposure divided by the concentration 

in the surrounding water at the same time or during the same period. 

Cancer Effect Level (CEL)-The lowest dose of chemical in a study, or group of studies, that 

produces significant increases in the incidence of cancer (or tumors) between the exposed population 

and its appropriate control. 

Carcinogen-A chemical capable of inducing cancer. 

Ceiling Value-A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure- Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Developmental Toxicity-The occurrence of adverse effects on the developing organism that may 

result from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any 

point in the life span of the organism. 

Embryotoxicity and Fetotoxicity-Any toxic effect on the conceptus as a result of prenatal exposure 

to a chemical; the distinguishing feature between the two terms is the stage of development during 

which the insult occurred. The terms, as used here, include malformations and variations, altered 

growth, and in utero death. 

EPA Health Advisory-An estimate of acceptable drinking water levels for a chemical substance 

based on health effects information. A health advisory is not a legally enforceable federal standard, 

but serves as technical guidance to assist federal, state, and local officials. 

Immediately Dangerous to Life or Health (IDLH)-The maximum environmental concentration of a 

contaminant from which one could escape within 30 min without any escape-impairing symptoms or 

irreversible health effects. 
DICHLORVOS 200 

9. GLOSSARY 

Intermediate Exposure-Exposure to a chemical for a duration of 15-364 days. as specified in the 

Toxicological Profiles. 

Immunologic Toxicity- The occurrence of adverse effects on the immune system that may result 

from exposure to environmental agents such as chemicals. 

In Vitro-Isolated from the living organism and artificially maintained, as in a test tube. 

In Viva-Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)-The lowest concentration of a chemical in air which has been 

reported to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)-A calculated concentration of a chemical in air to which exposure 

for a specific length of time 1s expected to cause death in 50% of a defined experimental animal 

population. 

Lethal Dose(LO) (LDLO)-The lowest dose of a chemical introduced by a route other than inhalation 

that is expected to have caused death in humans or animals. 

Lethal Dose(50) (LD50)-The dose of a chemical which has been calculated to cause death in 50% of 

a defined experimental animal population. 

Lethal Time(50) (LT50)-A calculated period of time within which a specific concentration of a 

chemical is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)-The lowest dose of chemical in a study, or 

group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Malformations-Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level-An estimate of daily human exposure to a dose of a chemical that is likely to 

be without an appreciable risk of adverse noncancerous effects over a specified duration of exposure. 

Mutagen-A substance that causes mutations. A mutation is a change in the genetic material in a 

body cell. Mutations can lead to birth defects, miscarriages, or cancer. 

Neurotoxicity-The occurrence of adverse effects on the nervous system following exposure to 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)-The dose of chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen 

between the exposed population and its appropriate control. Effects may be produced at this dose, but 

they are not considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)-The equilibrium ratio of the concentrations of a 

chemical in n-octanol and water, in dilute solution. 
DICHLORVOS 201 

9. GLOSSARY 

Permissible Exposure Limit (PEL)-An allowable exposure level in workplace air averaged over an 

8-hour shift. 

q1*-The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The ql* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually pg/L for water, mg/kg/day for food, and 

pg/m3

 for air). 

Reference Dose (RfD)-An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of 

deleterious effects during a lifetime. The RfD is operationally derived from the NOAEL (from animal 

and human studies) by a consistent application of uncertainty factors that reflect various types of data 

used to estimate RfDs and an additional modifying factor, which is based on a professional judgment 

of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects such as 

cancer. 

Reportable Quantity (RQ)-The quantity of a hazardous substance that is considered reportable 

under CERCLA. Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an 

amount established by regulation either under CERCLA or under Sect. 3 11 of the Clean Water Act. 

Quantities are measured over a 24-hour period. 

Reproductive Toxicity-The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the 

related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual 

behavior, fertility, pregnancy outcomes, or modifications in other functions that are dependent on the 

integrity of this system. 

Short-Term Exposure Limit (STEL)-The maximum concentration to which workers can be exposed 

for up to 15 min continually. No more than four excursions are allowed per day, and there must be at 

least 60 min between exposure periods. The daily TLV-TWA may not be exceeded. 

Target Organ Toxicity- This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single 

limited exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen-A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)-A concentration of a substance to which most workers can be 

exposed without adverse effect. The TLV may be expressed as a TWA, as a STEL, or as a CL. 

Time-Weighted Average (TWA)-An allowable exposure concentration averaged over a normal 8­

hour work-day or 40-hour workweek. 

Toxic Dose (TD50)-A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Uncertainty Factor (UF)-A factor used in operationally deriving the RfD from experimental data. 

UFs are intended to account for (1) the variation in sensitivity among the members of the human 

population, (2) the uncertainty- in extrapolating animal data to the case of human, (3) the uncertainty in 
DICHLORVOS 202 

9. GLOSSARY 

extrapolating from data obtained in a study that is of less than lifetime exposure, and (4) the 

uncertainty in using LOAEL data rather than NOAEL data. Usually each of these factors is set equal 

to 10. 
DICHLORVOS A-1 

ATSDR MINIMAL RISK LEVEL
 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorizarion Act (SARA) [Pub. L. 

99-4991, requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop 

jointly with the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous 

substances most commonly found at facilities on the CERCLA National Priorities List (NPL); prepare 

toxicological profiles for each substance included on the priority list of hazardous substances; and 

assure the initiation of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available 

toxicological information and epidemiologic evaluations of a hazardous substance. During the 

development of toxicological profiles Minimal Risk Levels (MRLs) are derived when reliable and 

sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a 

specific duration for a given route of exposure. An MRL is an estimate of the daily human exposure 

to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health 

effects over a specified duration of exposure. MRLs are based on noncancer health effects only and 

are not based on a consideration of cancer effects. These substance-specific estimates, which are 

intended to serve as screening levels, are used by ATSDR health assessors to identify contaminants 

and potential health effects that may be of concern at hazardous waste sites. It is important to note 

that MRLs are not intended to define clean-up or action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect-level/uncertainty 

factor approach. They are below levels that might cause adverse health effects in the people most 

sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate ( 15 

364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of 

exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not 

yet identified a method suitable for this route of exposure. MRLs are generally based on the most 

sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects 

(such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for 

establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will 

occur. 

MRLs are intended only to serve as a screening tool to help public health professionals decide where 

to look more closely. They may also be viewed as a mechanism to identify those hazardous waste 
DICHLORVOS A-2 

APPENDIX A 

sites that are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty 

because of the lack of precise toxicological information on the people who might be most sensitive 

(e.g., infants, elderly, nutritionally or immunologically compromised) to the effects of hazardous 

substances. ATSDR uses a conservative (i.e., protective) approach to address this uncertainty 

consistent with the public health principle of prevention. Although human data are preferred, MRLs 

often must be based on animal studies because relevant human studies are lacking. In the absence of 

evidence to the contrary, ATSDR assumes that humans are more sensitive to the effects of hazardous 

substances than animals and that certain persons may be particularly sensitive. Thus, the resulting 

MRL may be as much as a hundredfold below levels that have been shown to be nontoxic in 

laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within 

the Division of Toxicology, expert panel peer reviews, and agencywide MRL Workgroup reviews, 

with participation from other federal agencies and comments from the public. They are subject to 

change as new information becomes available concomitant with updating the toxicological profiles. 

Thus MRLs in the most recent toxicological profiles supersede previously published levels. For 

additional information regarding MRLs, please contact the Division of Toxicology, Agency for Toxic 

Substances and Disease Registry, 1600 Clifton Road, Mailstop E29, Atlanta, Georgia 30333. 














 DICHLORVOS B-l 

APPENDIX B 

USER’S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it 

would still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence 

that will direct the reader to chapters in the profile that will provide more information on the given 

topic. 

Chapter 2 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (2-1, 2-2, and 2-3) and figures (2-1 and 2-2) are used to summarize health effects and illustrate 

graphically levels of exposure associated with those effects. These levels cover health effects observed 

at increasing dose concentrations and durations, differences in response by species, minimal risk levels 

(MRLs) to humans for noncancer endpoints, and EPA’s estimated range associated with an upperbound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and 

figures for a quick review of the health effects and to locate data for a specific exposure scenario. The 

LSE tables and figures should always be used in conjunction with the text. All entries in these tables 

and figures represent studies that provide reliable, quantitative estimates of No-Observed-AdverseEffect Levels (NOAELs), Lowest-Observed- Adverse-Effect Levels (LOAELs), or Cancer Effect 

Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 2-l and Figure 2-l are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See LSE Table 2-1 

(1) Route of Exuosure One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. When 

sufficient data exist, three LSE tables and two LSE figures are presented in the document. The 

three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and 

dermal (LSE Table 2-1, 2-2, and 2-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 2-l) and oral (LSE Figure 2-2) routes. Not all substances will have data on each 

route of exposure and will not therefore have all five of the tables and figures. 

(2) Exuosure Period Three exposure periods - acute (less than 15 days), intermediate (1.5-364 days), 

and chronic (365 days or more) are presented within each relevant route of exposure. In this 

example, an inhalation study of intermediate exposure duration is reported. For quick reference 
DICHLORVOS B-2 

APPENDIX B 

to health effects occurring from a known length of exposure, locate the applicable exposure 

period within the LSE table and figure. 

(3)	 Health Effect The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the “System” column of the LSE table (see key number 

18). 

(4)	 Key to Figure Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the 2 “18r” data points in Figure 2-l). 

(5)	 Species The test species, whether animal or human, are identified in this column. Section 2.4, 

“Relevance to Public Health,” covers the relevance of animal data to human toxicity and 

Section 2.3, “Toxicokinetics,” contains any available information on comparative 

toxicokinetics. Although NOAELs and LOAELs are species specific, the levels are 

extrapolated to equivalent human doses to derive an MRL. 

(6)	 Exposure Frequency/Duration The duration of the study and the weekly and daily exposure 

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to toxaphene via inhalation 

for 6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the dosing 

regimen refer to the appropriate sections of the text or the original reference paper, i.e., 

Nitschke et al. 1981. 

(7)	 System This column further defines the systemic effects. These systems include: respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. “Other” refers to any systemic effect (e.g., a decrease in body weight) not 

covered in these systems. In the example of key number 18, 1 systemic effect (respiratory) was 

investigated. 

(8)	 NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at 

which no harmful effects were seen in the organ system studied. Key number 18 reports 

a’NOAEL of 3 ppm for the respiratory system which was used to derive an intermediate 

exposure, inhalation MRL of 0.0005 ppm (see footnote ‘lb”). 

(9)	 LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the 

study that caused a harmful health effect. LOAELs have been classified into “Less Serious” 

and “Serious” effects. These distinctions help readers identify the levels of exposure at which 

adverse health effects first appear and the gradation of effects with increasing dose. A brief 

description of the specific endpoint used to quantify the adverse effect accompames the 

LOAEL. The respiratory effect reported in key number 18 (hyperplasia) is a Less serious 

LOAEL of 10 ppm. MRLs are not derived from Serious LOAELs. 

(10) Reference The complete reference citation is given in chapter 8 of the profile. 

(11) CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of 

carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious 
DICHLORVOS B-3 

APPENDIX B 

effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report 

doses not causing measurable cancer increases. 

(12) Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote “b” indicates the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.0005 ppm. 

LEGEND 

See Figure 2-1 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13) Exposure Period The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the intermediate and chronic exposure periods are illustrated. 

(14) Health Effect These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15) Levels of Exposure concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the 

log scale “y” axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is 

reported in mg/kg/day . 

(16) NOAEL In this example, 1% NOAEL is the critical endpoint for which an intermediate 

inhalation exposure MRL is based. As you can see from the LSE figure key, the open-circle 

symbol indicates to a NOAEL for the test species-rat. The key number 18 corresponds to the 

entry in the LSE table. The dashed descending arrow indicates the extrapolation from the 

exposure level of 3 ppm (see entry 18 in the Table) to the MRL of 0.0005 ppm (see footnote 

“b” in the LSE table). 

(17) CEL Key number 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The 

diamond symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 

corresponds to the entry in the LSE table. 

(18) Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the 

upper-bound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are 

derived from the EPA’s Human Health Assessment Group’s upper-bound estimates of the slope 

of the cancer dose response curve at low dose levels (ql*). 

(19) Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. 


DICHLORVOS B-6 

APPENDIX B 

Chapter 2 (Section 2.4) 

Relevance to Public Health 

The Relevance to Public Health section provides a health effects summary based on evaluations of 

existing toxicologic, epidemiologic, and toxicokinetic information. This summary is designed to 

present interpretive, weight-of-evidence discussions for human health endpoints by addressing the 

following questions. 

1. What effects are known to occur in humans? 

2 . What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around hazardous

 waste sites? 

The section covers endpoints in the same order they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data 

are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In 

vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this section. If data are located in the scientific literature, a table of genotoxicity 

information is included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer endpoints (if 

derived) and the endpoints from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to 

public health are identified in the Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for 

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). 

These MRLs are not meant to support regulatory action; but to acquaint health professionals with 

exposure levels at which adverse health effects are not expected to occur in humans. They should 

help physicians and public health officials determine the safety of a community living near a chemical 

emission, given the concentration of a contaminant in air or the estimated daily dose in water. MRLs 

are based largely on toxicological studies in animals and on reports of human occupational exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. 

Chapter 2.4, “Relevance to Public Health,” contains basic information known about the substance. 

Other sections such as 2.6, “Interactions with Other Substances,” and 2.7, “Populations that are 

Unusually Susceptible” provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 
DICHLORVOS B-7 

APPENDIX B 

To derive an MRL, ATSDR generally selects the most sensitive endpoint which, in its best judgement. 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is 

available for all potential systemic, neurological, and developmental effects. If this information and 

reliable quantitative data on the chosen endpoint are available, ATSDR derives an MRL using the 

most sensitive species (when information from multiple species is available) with the highest NOAEL 

that does not exceed any adverse effect levels. When a NOAEL is not available, a lowest-observedadverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor (UF) of 10 

must be employed. Additional uncertainty factors of 10 must be used both for human variability to 

protect sensitive subpopulations (people who are most susceptible to the health effects caused by the 

substance) and for interspecies variability (extrapolation from animals to humans). In deriving an 

MRL, these individual uncertainty factors are multiplied together. The product is then divided into the 

inhalation concentration or oral dosage selected from the study. Uncertainty factors used in developing 

a substance-specific MRL are provided in the footnotes of the LSE Tables.