Dichlorvos (EHC 79, 1988)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

ENVIRONMENTAL HEALTH CRITERIA 79

DICHLORVOS

This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization.

First draft prepared by Dr. J. Sekizawa
(National Institute of Hygienic Sciences, Japan)
and Dr. M. Eto (Kyushu University, Japan) with
the assistance of Dr. J. Miyamoto and
Dr. M. Matsuo (Sumitomo Chemical Company)

Published under the joint sponsorship of
the United Nations Environment Programme,
the International Labour Organisation,
and the World Health Organization

World Health Orgnization
Geneva, 1989

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR DICHLORVOS

1. SUMMARY AND RECOMMENDATIONS

1.1. General
1.2. Environmental transport, distribution, and transformation
1.3. Environmental levels and human exposure
1.4. Kinetics and metabolism
1.5. Effects on organisms in the environment
1.6. Effects on experimental animals and in vitro test systems
1.7. Effects on man

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1. Identity
2.2. Physical and chemical properties
2.3. Conversion factors
2.4. Analytical methods
2.4.1. Sampling methods
2.4.1.1 Food and feed
2.4.1.2 Blood
2.4.1.3 Air
2.4.2. Analytical methods
2.4.2.1 Analysis of technical and formulated
dichlorvos products
2.4.2.2 Determination of dichlorvos residues
2.4.2.3 Confirmatory tests
2.4.2.4 Food
2.4.2.5 Blood
2.4.2.6 Air
2.4.2.7 Soil and water

3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1. Natural occurrence
3.2. Man-made sources
3.2.1. Production levels and processes
3.2.1.1 Worldwide production figures
3.2.1.2 Manufacturing process
3.2.2. Uses
3.2.3. Accidental release

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

4.1. Transport and distribution between media
4.2. Biotransformation
4.2.1. Abiotic degradation
4.2.2. Biodegradation
4.2.3. Bioaccumulation and biomagnification
4.3. Ultimate fate following use

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1. Environmental levels
5.1.1. Air
5.1.2. Food
5.2. General population exposure
5.3. Occupational exposure during manufacture, formulation, or use
5.3.1. Air

6. KINETICS AND METABOLISM

6.1. Absorption
6.1.1. Human studies
6.2. Distribution
6.2.1. Studies on experimental animals
6.2.1.1 Oral
6.2.1.2 Inhalation
6.2.1.3 Intraperitoneal
6.2.1.4 Intravenous
6.3. Metabolic transformation
6.3.1. Metabolites
6.4. Elimination and excretion in expired air, faeces, and urine
6.4.1. Human studies
6.4.2. Studies on experimental animals
6.4.2.1 Oral
6.4.2.2 Parenteral
6.5. Retention and turnover
6.5.1. Biological half-life
6.5.2. Body burden
6.5.3. Indicator media

7. EFFECTS ON ORGANISMS IN THE ENVIRONMENT

7.1. Microorganisms
7.1.1. Algae and plankton
7.1.2. Fungi
7.1.3. Bacteria
7.2. Aquatic organisms
7.2.1. Fish
7.2.1.1 Acute toxicity
7.2.1.2 Short-term toxicity
7.2.2. Invertebrates
7.3. Terrestrial organisms
7.3.1. Birds
7.3.1.1 Acute oral toxicity
7.3.1.2 Short-term toxicity
7.3.1.3 Field experience
7.3.2. Invertebrates
7.3.3. Honey bees
7.3.4. Miscellaneous

8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

8.1. Single exposures
8.1.1. Domestic animals
8.1.2. Potentiation

8.2. Short-term exposures
8.2.1. Oral
8.2.1.1 Mouse
8.2.1.2 Rat
8.2.1.3 Rabbit
8.2.1.4 Cat
8.2.1.5 Dog
8.2.1.6 Pig
8.2.1.7 Cow
8.2.2. Dermal
8.2.2.1 Rat
8.2.2.2 Livestock
8.2.3. Inhalation
8.2.3.1 Experimental animals
8.2.3.2 Domestic animals
8.2.4. Studies on ChE activity
8.3. Skin and eye irritation; sensitization
8.4. Long-term exposure
8.4.1. Oral
8.4.1.1 Rat
8.4.1.2 Dog
8.4.2. Inhalation
8.4.2.1 Rat
8.5. Reproduction, embryotoxicity, and teratogenicity
8.5.1. Reproduction
8.5.1.1 Effects on testes
8.5.1.2 Effect on estrous cycle
8.5.1.3 Domestic animals
8.5.2. Embryotoxicity and teratogenicity
8.5.2.1 Oral
8.5.2.2 Inhalation
8.5.2.3 Intraperitoneal
8.5.3. Résumé of reproduction, embryotoxicity, and
teratogenicity studies
8.6. Mutagenicity and related end-points
8.6.1. Methylating reactivity
8.6.1.1 In vitro studies
8.6.1.2 In vivo studies
8.6.1.3 Discussion of methylating reactivity
8.6.2. Mutagenicity
8.6.2.1 In vitro studies
8.6.2.2 In vivo studies
8.7. Carcinogenicity
8.7.1. Oral
8.7.1.1 Mouse
8.7.1.2 Rat
8.7.2. Inhalation
8.7.2.1 Rat
8.7.3. Appraisal of carcinogenicity
8.8. Mechanisms of toxicity; mode of action
8.9. Neurotoxicity
8.9.1. Delayed neurotoxicity
8.9.2. Mechanism of neurotoxicity
8.10. Other studies
8.10.1. Immunosuppressive action

8.11. Factors modifying toxicity; toxicity of metabolites
8.11.1. Factors modifying toxicity
8.11.2. Toxicity of metabolites
8.11.2.1 Acute toxicity
8.11.2.2 Short-term exposures
8.11.2.3 Long-term exposure
8.11.2.4 Mutagenicity
8.11.2.5 Metabolism

9. EFFECTS ON MAN

9.1. General population exposure
9.1.1. Acute toxicity
9.1.1.1 Poisoning incidents
9.1.2. Effects of short- and long-term exposure
9.1.2.1 Studies on volunteers
9.1.2.2 Hospitalized patients
9.2. Occupational exposure
9.2.1. Acute toxicity
9.2.1.1 Poisoning incidents
9.2.2. Effects of short- and long-term exposure
9.2.2.1 Pesticide operators and factory workers
9.2.2.2 Mixed exposure

10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT

10.1. Evaluation of human health risks
10.2. Evaluation of effects on the environment
10.3. Conclusions

11. RECOMMENDATIONS

12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

REFERENCES

WHO TASK GROUP ON DICHLORVOS

Members
Dr L. Albert, Environmental Pollution Programme, National Institute of
Biological Resource Research, Veracruz, Mexico
Dr E. Budd, Office of Pesticide Programs, US Environmental Protection
Agency, Washington DC, USA
Mr T.P. Bwititi, Ministry of Health, Causeway, Harare, Zimbabwe
Dr S. Deema, Ministry of Agriculture and Cooperatives, Bangkok,
Thailand
Dr I. Desi, Department of Hygiene and Epidemiology, Szeged University
Medical School, Szeged, Hungary
Dr A.K.H. El Sebae, Pesticides Division, Faculty of Agriculture,
Alexandria University, Alexandria, Egypt
Dr R. Goulding, Keats House, Guy's Hospital, London, United Kingdom
(Chairman)
Dr J. Jeyaratnam, National University of Singapore, Department of
Social Medicine and Public Health, Faculty of Medicine, National
University Hospital, Singapore (Vice-Chairman)
Dr Y. Osman, Occupational Health Department, Ministry of Health,
Khartoum, Sudan
Dr A. Takanaka, Division of Pharmacology, National Institute of
Hygienic Sciences, Tokyo, Japan

Observers
Dr N. Punja, European Chemical Industry, Ecology and Toxicology Centre
(ECETOC), Brussels, Belgium
Ms J. Shaw, International Group of National Associations of
Manufacturers of Agrochemical Products (GIFAP), Brussels, Belgium

Secretariat
Dr M. Gilbert, International Register of Potentially Toxic Chemicals,
United Nations Environment Programme, Geneva, Switzerland
Dr K.W. Jager, International Programme on Chemical Safety, World Health
Organization, Geneva, Switzerland (Secretary)
Dr T. Ng, Office of Occupational Health, World Health
Organization, Geneva, Switzerland
Dr G. Quélennec, Pesticides Development and Safe Use Unit, World Health
Organization, Geneva, Switzerland
Dr R.C. Tincknell, Beaconsfield, Buckinghamshire, United Kingdom
(Temporary Adviser)
Dr G.J. Van Esch, Bilthoven, Netherlands (Temporary Adviser) (Co-
Rapporteur)
Dr E.A.H. Van Heemstra-Lequin, Laren, Netherlands (Temporary Adviser)
(Co-Rapporteur)

NOTE TO READERS OF THE CRITERIA DOCUMENTS

Every effort has been made to present information in the criteria
documents as accurately as possible without unduly delaying their
publication. In the interest of all users of the environmental health
criteria documents, readers are kindly requested to communicate any
errors that may have occurred to the Manager of the International
Programme on Chemical Safety, World Health Organization, Geneva,
Switzerland, in order that they may be included in corrigenda, which
will appear in subsequent volumes.

* * *

A detailed data profile and a legal file can be obtained from the
International Register of Potentially Toxic Chemicals, Palais des
Nations, 1211 Geneva 10, Switzerland (Telephone no. 988400 - 985850).

ENVIRONMENTAL HEALTH CRITERIA FOR DICHLORVOS

A WHO Task Group on Environmental Health Criteria for Dichlorvos
met in Geneva from 1 to 5 December 1986. Dr M. Mercier, Manager, IPCS,
opened the meeting and welcomed the participants on behalf of the heads
of the three IPCS co-sponsoring organizations (UNEP/ILO/WHO). The
Group reviewed and revised the draft criteria document and made an
evaluation of the risks for human health and the environment from
exposure to dichlorvos.

The drafts of the document were prepared by DR E.A.H. VAN
HEEMSTRA-LEQUIN and DR G.J. VAN ESCH of the Netherlands.

Draft summaries of Japanese studies on dichlorvos were prepared and
finalized by DR M. ETO (Kyushu University), and DR J. MIYAMOTO and
DR M. MATSUO (Sumitomo Chemical Co., Ltd), with the assistance of the
staff of the NATIONAL INSTITUTE OF HYGIENIC SCIENCES, Tokyo,
Japan and DR I. YAMAMOTO (Tokyo University of Agriculture).

The proprietary data mentioned in the document were made available
to the Central Unit of the IPCS by Temana International Ltd, Richmond,
United Kingdom for evaluation by the Task Group.

The efforts of all who helped in the preparation and finalization
of the document are gratefully acknowledged.

* * *

The proprietary information contained in this document cannot
replace documentation for registration purposes, because the latter has
to be closely linked to the source, the manufacturing route, and the
purity/impurities of the substance to be registered. The data should
be used in accordance with paragraphs 82-84 and recommendation
paragraph 90 of the 2nd FAO Government Consultation (FAO, 1982).

* * *

Partial financial support for the publication of this criteria
document was kindly provided by the United States Department of Health
and Human Services, through a contract from the National Institute of
Environmental Health Sciences, Research Triangle Park, North Carolina,
USA - a WHO Collaborating Centre for Environmental Health Effects. The
United Kingdom Department of Health and Social Security generously
supported the cost of printing.

1. SUMMARY AND RECOMMENDATIONS

1.1 General

Dichlorvos, an organophosphate, is a direct-acting cholinesterase
(ChE)^a inhibitor. Since 1961, it has been commercially manufactured
and used throughout the world as a contact and stomach insecticide. It
is used to protect stored products and crops (mainly in greenhouses),
and to control internal and external parasites in livestock (granules
of impregnated resin) and insects in houses, buildings, aircraft, and
outdoor areas (as aerosols, liquid sprays, or impregnated cellulosic,
ceramic, or resin strips). The present worldwide production of
dichlorvos is about 4 million kg per year.

The purity of the technical grade product is at least 97%, and the
type of impurities depends on the manufacturing process. In the
presence of moisture, dichlorvos breaks down to form acidic products
that are eventually mineralized. Technical dichlorvos may be stabil-
ized, which improves the storage stability, but it is not normally
necessary to stabilize high purity products. In the past, 2 - 4%
epichlorohydrin has been used for this purpose. Dichlorvos is soluble
in water and miscible with most organic solvents and aerosol
propellants. The vapour pressure of dichlorvos is relatively high (1.6
Pa at 20 °C).

Methods for sampling and analysing dichlorvos in food, feed, and
the environment and for determining the inhibition of ChE activity in
blood, red blood cells, plasma, and brain are described.

1.2 Environmental Transport, Distribution, and Transformation

Dichlorvos is not directly applied to soil, but is added to water
to control invertebrate fish parasites encountered during intensive
fish farming. It breaks down rapidly in humid air, water, and soil,
both by abiotic and biotic processes, whereas on wooden surfaces it may
persist for a longer time (39% remaining after 33 days). It degrades
mainly to dichloro-ethanol, dichloroacetaldehyde (DCA), dichloroacetic
acid, dimethylphosphate, dimethylphosphoric acid, and other water-
soluble compounds, which are eventually mineralized.

Dichlorvos is rapidly lost from leaf surfaces by volatilization and
hydrolysis.

Accidental spillage of dichlorvos may have acute hazardous effects
on man and the environment. However, long-term effects are unlikely,
in view of the volatility and instability in humid environments.
Bioaccumulation or biomagnification do not occur.

------------------------------------------------------------------------
^a Cholinesterase is the enzyme which breaks down acetylcholine (ACh),
the transmitter at cholinergic nerve synapses.

1.3 Environmental Levels and Human Exposure

The indoor air dichlorvos concentrations resulting from house-
hold and public health use depend on the method of application, tem-
perature, and humidity. For example, one impregnated resin strip per
30 m³ results in concentrations of the order of 0.1 - 0.3 mg/m³ the
first week (the latter only in special circumstances), subsequently
decreasing to 0.02 mg/m³ or less over the next few weeks.

Dichlorvos residues in food commodities are generally low and are
readily destroyed during processing. The metabolite DCA may also be
present in detectable amounts. Total-diet studies in the United
Kingdom and the USA have confirmed that no, or very little, dichlorvos
is found in prepared meals.

Exposure of the general population via food and drinking-water as a
result of agricultural or post-harvest use of dichlorvos is negligible.
However, household and public health use do give rise to exposure,
principally through inhalation and dermal absorption.

Similar routes of exposure occur in professional pest
control with dichlorvos. In warehouses, mushroom houses, and
greenhouses, the concentrations of dichlorvos in the air are in general
below 1 mg/m³ when the recommended application rates are used, but in
certain circumstances they may rise considerably above this level.

1.4 Kinetics and Metabolism

Dichlorvos is readily absorbed via all routes of exposure. After
oral administration, it is metabolized in the liver before it reaches
the systemic circulation.

One hour after the oral administration of ³²P-dichlorvos, maximum
concentrations of radioactivity are found in the kidneys, liver,
stomach, and intestines. In bone, the increase is slower, due to
inorganic phosphate entering the phosphate pool of the organism.

Pigs administered a single oral dose of ¹⁴C-labelled dichlorvos as
a slow-release polyvinyl chloride (PVC) formulation, showed
radioactivity in all tissues, the highest level being in the liver
after 2 days, and the lowest being in the brain. Pregnant sows were
fed vinyl-1-¹⁴C-dichlorvos or ³⁶Cl-dichlorvos in PVC pellets at 4 mg
dichlorvos/kg body weight per day during the last third of the
gestation period. Although the tissues of the sows and piglets
contained ¹⁴C or ³⁶Cl ranging from 0.3 to 18 mg/kg tissue, no
radioactivity was associated with dichlorvos or its primary
metabolites.

Up to 70% of the dichlorvos inhaled by pigs is taken up into the
body. When rats and mice inhaled dichlorvos (90 mg/m³ for 4 h), none
or very little (up to 0.2 mg/kg) was found in blood, liver, testes,
lung, or brain. The highest concentrations (up to 2.4 mg/kg tissue)
were found in kidneys and adipose tissue. Dichlorvos rapidly
disappeared from the kidneys with a half-life of approximately 14 min.

Dichlorvos is metabolized mainly in the liver via 2 enzymatic
pathways: one, producing desmethyldichlorvos, is glutathione dependent,
while the other, resulting in dimethyl-phosphate and DCA, is
glutathione independent. The metabolism of dichlorvos in various
species, including man, is rapid and uses similar pathways.
Differences between species relate to the rate of metabolism rather
than to a difference of metabolites.

The major route of metabolism of the vinyl portion of dichlorvos
leads to (a) dichloroethanol glucuronide and (b) hippuric acid, urea,
carbon dioxide, and other endogenous chemicals, such as glycine and
serine, which give rise to high levels of radioactivity in the tissues.
No evidence of the accumulation of dichlorvos or potentially toxic
metabolites has been found.

The major route for the elimination of the phosphorus-containing
moiety is via the urine, with expired air being a less important route.
However, the vinyl moiety is mainly eliminated in the expired air, and
less so in the urine. In cows, elimination is roughly equally
distributed between urine and faeces.

1.5 Effects on Organisms in the Environment

The effect of dichlorvos on microorganisms is variable and species
dependent. Certain microorganisms have the ability to metabolize
dichlorvos but the pesticide may interfere with the endogenous
oxidative metabolism of the organism. In certain organisms it causes
growth inhibition, while in others it has no influence or may even
stimulate growth. Dichlorvos has little or no toxic effect on
microorganisms degrading organic matter in sewage. The above effects
have been seen over the wide dose range of 0.1 - 100 mg/litre.

The acute toxicity of dichlorvos for both freshwater and estuarine
species of fish is moderate to high (96-h LC₅₀ values range from 0.2
to approximately 10 mg/litre). Brain and liver ChE inhibition in
certain fish was found at dose levels of 0.25 - 1.25 mg/litre, but
recovery of ChE activity took place when they were returned to clean
water.

Invertebrates are more sensitive to dichlorvos. Levels above
0.05 µg/litre may have deleterious effects. Dichlorvos also has a
high oral toxicity for birds. The LD₅₀ values are in the range of
5 - 40 mg/kg body weight. In short-term dietary studies, the compound
was slightly to moderately toxic for birds. Brain ChE inhibition was
seen at 50 mg/kg diet or more and at 500 mg/kg diet, half of the birds
died. There have been instances when chickens and ducks have died
after accidental access to dichlorvos-contaminated feed and drinking-
water.

Dichlorvos is highly toxic for honey bees. The LD₅₀ by oral
administration is 0.29 µg/g bee, and after topical application is
0.65 µg/g bee.

1.6 Effects on Experimental Animals and In Vitro Test Systems

Dichlorvos is moderately to highly toxic when administered in single
doses to a variety of animal species by several routes. It directly
inhibits acetylcholinesterase (AChE) activity in the nervous system and
in other tissues. Maximum inhibition generally occurs within 1 h, and
is followed by rapid recovery. The oral LD₅₀ for the rat is 30 - 110
mg/kg body weight, depending on the solvent used. The hazard
classification of dichlorvos by WHO (1986a) is based on an oral
LD₅₀ for the rat of 56 mg/kg body weight. The signs of intoxication
are typical of organophosphorus poisoning, i.e., salivation,
lachrymation, diarrhoea, tremors, and terminal convulsions, with death
occurring from respiratory failure. The signs of intoxication are
usually apparent shortly after dosing, and, at lethal doses, death
occurs within 1 h. Survivors recover completely within 24 h.

Potentiation is slight when dichlorvos is given orally in
combination with other organophosphates, but in combination with
malathion it is marked.

In short-term toxicity studies on the mouse, rat, dog, pig, and
monkey, inhibition of plasma, red blood cell, and brain ChE are the most
important signs of toxicity. After oral administration, approximately
0.5 mg/kg body weight (range, 0.3 - 0.7 mg/kg) did not produce ChE
inhibition. In a 2-year study on dogs, ChE inhibition was noted at
3.2 mg/kg body weight or more.

Flea collar dermatitis has been described in dogs and cats wearing
dichlorvos-impregnated PVC flea collars. This was a primary irritant
contact dermatitis which may have been caused by dichlorvos.

Many short-term inhalation studies on different animal species have
been carried out. Air concentrations in the range of 0.2 - 1 mg/m³ do
not affect ChE activity significantly. Other effects, such as growth
inhibition and increase in liver weight have been reported at dose
levels at least 10 - 20 times higher.

It is possible to produce clinical neuropathy in hens, but the doses
of dichlorvos required are far in excess of the LD₅₀. The effects are
associated with high inhibition of neurotoxic esterase (NTE) in the
brain and spinal cord. In the rat, however, neuropathic changes in the
white matter of the brain have been reported following repeated daily
oral application of an LD₅₀ dose.

Immune suppression has been reported in rabbits. At present, no
evaluation as to the relevance for human beings can be given; more
attention to this aspect is needed.

In a long-term study, rats fed dichlorvos in the diet for 2 years
showed no signs of intoxication. Hepatocellular fatty vacuolization of
the liver and ChE inhibition were significant at the two highest dose
levels (2.5 and 12.5 mg/kg body weight).

In a carefully conducted long-term inhalation study on rats
with whole body exposure (23 h/day, for 2 years), results were compar-
able with those seen in the oral study. No effects were seen at
0.05 mg/m³; inhibition of ChE activity took place at 0.48 mg/m³ or
more.

In several reproduction studies on rats and domestic animals, no
effects were seen on reproduction, and there was no embryotoxicity at
dose levels that did not cause maternal toxicity. At toxic doses,
dichlorvos may cause reversible disturbances of spermatogenesis in mice
and rats. It was not teratogenic in several studies carried out on
rats and rabbits.

Dichlorvos is an alkylating agent and binds in vitro to bacterial
and mammalian nucleic acids. It is mutagenic in a number of microbial
systems, but there is no evidence of mutagenicity in intact mammals,
where it is rapidly degraded by esterases in blood and other tissues.

Dichlorvos carcinogenicity has been investigated in mice (oral
studies) and rats (oral and inhalation studies). The dose levels used
in 2-year oral studies were up to 800 mg/litre drinking-water or
600 mg/kg diet for mice, and up to 280 mg/litre drinking-water or
234 mg/kg diet for rats. In a rat inhalation study, dichlorvos
concentrations in air of up to 4.7 mg/m³ were tested for 2 years. No
statistically significant increase in tumour incidence was found. In
two recent carcinogenicity studies on mice and rats, dichlorvos was
administered by intubation at dose levels between 10 and 40 mg/kg body
weight (mice) and 4 and 8 mg/kg body weight (rat) for up to 2 years.
Only preliminary information has been provided. The evidence for
carcinogenicity in these new studies is difficult to interpret at this
time. Only when complete and final reports become available will it be
possible to draw more definitive conclusions (in this context, see
footnote section 8.7.3).

From acute and short-term studies, it is clear that the metabolites
of dichlorvos are all less toxic than the parent compound. Only DCA
was positive in a few mutagenicity tests.

1.7 Effects on Man

A fatal case of dichlorvos poisoning has been described in the
general population: despite correct treatment, a suicide succeeded with
approximately 400 mg dichlorvos/kg body weight. In another poisoning
case, a woman ingested about 100 mg dichlorvos/kg and survived,
following intensive care for 14 days. Two workers who had skin
exposure to a concentrated dichlorvos formulation, and failed to wash
it off, died of poisoning.

There have been two clinical reports describing four patients
suffering from severe poisoning from dichlorvos, taken orally, who
survived after treatment and who showed delayed neurotoxic effects.
Thus although the possibility of neuropathy in man cannot be excluded,
it is likely to occur only after almost lethal oral doses.

Since the 1960s, field studies in malaria control have been carried
out and the interiors of aircraft have been sprayed with dichlorvos.
Exposure to concentrations in the air of up to 0.5 mg/m³ were without
clinical effects, and no, or only insignificant, inhibition of blood
ChE activity was noted.

When dichlorvos was administered orally to human volunteers (single
or repeated doses of a slow-release PVC formulation), significant
inhibition of red blood cell ChE activity was found at 4 mg/kg body
weight or more. At 1 mg/kg body weight or more, plasma ChE activity
was significantly inhibited. Daily oral doses of 2 mg
dichlorvos/person for 28 days reduced plasma ChE activity by 30%, but
red cell ChE activity was unaffected.

Human volunteers who were exposed to dichlorvos by inhalation for a
certain period per day for a number of consecutive days or weeks showed
ChE inhibition at a concentration of 1 mg/m³ or more, but not at
0.5 mg/m³. These results were confirmed in studies with pesticide
operators who came into contact with dichlorvos.

Hospitalized patients showed similar results after oral
administration or exposure by inhalation. Sick adults and children and
healthy pregnant women and babies in hospital wards treated with
dichlorvos strips (1 strip/30 or 40 m³) displayed normal ChE
activity. Only subjects exposed 24 h/day to concentrations above
0.1 mg/m³ or patients with liver insufficiency showed a moderate
decrease in plasma ChE activity.

No significant effects on plasma or red blood cell ChE activity
were observed in people exposed to the recommended rate of one
dichlorvos strip per 30 m³ in their homes over a period of 6 months,
even when the strips were replaced at shorter intervals than that
normally recommended. The maximum average concentration in the air was
approximately 0.1 mg/m³.

In factory workers exposed to an average of 0.7 mg/m³ for 8
months, significant inhibition of plasma and red blood cell ChE
activity was found.

Cases of dermatitis and skin sensitization due to dichlorvos have
been described in workers handling and spraying different types of
pesticides. In addition cross-sensitization with certain pesticides
has been seen.

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1 Identity

Primary constituent

Chemical structure: O
||
Cl₂C=CHOP(OCH₃)₂

Chemical formula: C₄H₇Cl₂O₄P

Chemical names: 2,2-dichloroethenyl dimethylphosphate (CAS);
2,2-dichlorovinyl dimethylphosphate (IUPAC)

Common synonyms: Bayer-19149, DDVF, DDVP, ENT-20738,
OMS-14, SD 1750, C-177

CAS registry number: 62-73-7

Technical product

Common trade names: Dedevap, Nogos, Nuvan, Phosvit, Vapona^a

Purity: should not be less than 97% (WHO, 1985)

Impurities: depend on the manufacturing process (section
3.2.1.2)

Additives: In the presence of traces of moisture,
dichlorvos slowly breaks down to form acidic
products that catalyse further decomposition
of the compound. In the past, 2 - 4%
epichlorohydrin was added to stabilize the
technical grade product (Melnikov, 1971).
Other stabilizers may now be used in some
products, but improved technology and purity
has largely eliminated the need for
stabilizers.

2.2 Physical and Chemical Properties

Dichlorvos is a colourless to amber liquid with an aromatic odour.

Some physical and chemical properties of dichlorvos are given in
Table 1.

----------------------------------------------------------------------------
^a The Shell trademark Vapona was formerly used exclusively for dichlorvos
and dichlorvos-containing formulations. More recently, this trademark
has been used more widely to include formulations containing other
active ingredients.

Table 1. Some physical and chemical properties of dichlorvos^a
-----------------------------------------------------------------------------
Relative molecular mass 221

Boiling point 35 °C at 6.7 Pa (0.05 mmHg);
74 °C at 133 Pa (1 mmHg)^b

Vapour pressure (20 °C) 1.6 Pa (1.2 x 10-2 mmHg)

Density (25 °C) 1.415

Refractive index N_D²⁵ = 1.4523

Solubility about 10 g/litre water at 20 °C; 2 -
3 g/kg kerosene; miscible with most
organic solvents and aerosol propel-
lants

Stability dichlorvos is stable to heat but is
hydrolysed by water; a saturated
aqueous solution at room temperature
is converted to dimethylphosphate and
dichloroacetaldehyde at a rate of
about 3% per day, more rapidly in
alkali

Corrosivity corrosive to iron and mild steel

Log n-octanol/water partition 1.47^c
coefficient
-----------------------------------------------------------------------------
^a From: Worthing & Walker (1983).
^b From: Melnikov (1971).
^c From: Bowman & Sans (1983).

2.3 Conversion Factors

1 ppm = 10 mg/m³ at 25 °C and 101 kPa (760 mmHg);

1 mg/m³ = 0.1 ppm

2.4 Analytical Methods

The various analytical methods are summarized in Tables 2, 3, 4,
and 5.

Table 2. Analytical methods for dichlorvos residues in food and biological
media recommended by the Codex Working Group on Methods of Analysis
---------------------------------------------------------------------------------------------------------
Sample Extraction Clean-up Detection and Recovery Limit of Reference
quantification detection
---------------------------------------------------------------------------------------------------------
grain methanol gas-liquid 0.02 mg/kg Anon. (1973)
chromatography
with thermionic
phosphorus
detector or
flame
photometric
phosphorus
detector

cereal petroleum ether/ Florisil gas chromato- 70 - 80% 0.0025 mg/kg Mestres et al.
products ethyl ether column graphy with (1979b)
flame photo-
metric detector
or thermionic
ionization
detector

cereals hexane activated gas chromato- 72 - 83% 0.01 ng Aoki et al.
hexane/aceto- charcoal graphy with (sensitivity) (1975)
nitrile benzene column flame photo-
extraction metric
acetone/ detection
hexane

crops dichloromethane steam gas-liquid 80 - 100% 0.01 mg/kg Elgar et al.
or ethylacetate distil- chromato- (1970)
lation graphy with
flame photo-
metric
detector,
thermionic
ionization
detector, or
electron
capture
detector

Table 2 (contd.)
---------------------------------------------------------------------------------------------------------
Sample Extraction Clean-up Detection and Recovery Limit of Reference
quantification detection
---------------------------------------------------------------------------------------------------------

ethylacetate/ Florisil gas chromato- 80% 0.002 - 0.05 Mestres et al.
dichloromethane column graphy with mg/kg (1979a)
flame photo-
metric detector

fruit and acetonitrile extraction gas-liquid approxi- Anon. (1977)
vegetables with chromato- mately 90%
chloroform; graphy with (at 0.5
residue flame photo- mg/kg)
in acetone metric detector
or thermionic
ionization
detector

onions acetonitrile amberlite gas chromato- 82% Iwata et al.
benzene XAD-8 graphy with (1981)
column flame photo-
benzene/ metric
dichloro- detection
methane

chloroform, HCl and gas-liquid approxi- 0.01 mg/kg Krause & Kirch-
methanol Celite chromatography mately 90% hoff (1970)
with thermionic (at 0.05 -
ionization 0.5 mg/kg)
detector

acetone and part- double gas-liquid 90% (at Luke et al.
ition with petro- concentration chromatography 0.1 mg/kg) (1981)
leum ether and with with flame
dichloromethane petroleum photometric
ether detector

eggplant water/methanol gas chromato- 95% 0.004 mg Nakamura &
fruit ether/petroleum graphy with Shiba (1980)
ether flame photo-
metric
detection

plants methanol ether/ gas-liquid 95 - 100% 0.1 mg/kg Dräger (1968)
petroleum chromatography
ether with phosphorus
detector

acetonitrile liquid-liquid thin-layer indo- bromo- Mendoza &
or partitioning chromatography phenyl- indoxyl- Shields (1971)
dichloromethane none enzymatic assay acetate acetate
or using: bee head 5 ng -
methanol/chloro- none extract, pig 5 ng 1 ng
form liver extract, 5 ng 0.1 ng
beef liver
extract

acetone or column thin-layer 1 - 2 ng Ambrus et al.
dichloromethane chromato- chromatography (1981)
graphy enzymatic
assay (horse
serum)

without thin-layer 100 ng
clean-up chromatography
silver nitrate
+ UV

gas-liquid 55 - 80% 0.1 - 1 ng
chromatography 0.01 - 0.05 ng
with thermionic typical limit
ionization of detection
detector or 0.005 - 0.02
electron mg/kg
capture
detector

vegetable acetone; dichloro- sweep co- gas chromato- 75 - 100% Eichner (1978)
and animal methane or aceto- distillation graphy with (at 0.03 -
food, nitrile; dichloro- thermionic 0.5 mg/kg)
tobacco methane phosphorus
detector

whole meal cereal: methanol; depending gas-liquid Abbott et al.
fats: hexane and on type chromatography (1970)
others: of sample with thermionic
acetonitrile phosphorus
detector,
caesium bromide
tips

homogenized silica gel gas chromato- 97 - 100% 0.005 mg/kg Dale et al.
sample, ethyl column; graphy with (sensitivity) (1973)
acetate-hexane elution flame
and HCl with acetone/ photometric
hexane detector

animal dichloromethane steam gas-liquid 80 - 100% 0.01 mg/kg Elgar et al.
tissues or ethylacetate distil- chromatography (1970)
lation with flame
photometric
detector,
thermionic
ionization
detector, or
electron
capture
detector

milk methanol acetonitrile gas chromato- 80 - 90% 0.01 mg/kg Dräger (1968)
and ether/ graphy with (at 0.01 -
petroleum phosphorus 0.1 mg/kg)
ether detector

acetonitrile dichloro- gas-liquid Abbott et al.
methane; chromatography (1970)
methane; with thermionic
residue phosphorus
dissolved detector,
in acetone caesium bromide
tips

Table 3. Other analytical methods for dichlorvos residues in food and biological media
---------------------------------------------------------------------------------------------------------
Sample Extraction Clean-up Detection and Recovery Limit of Reference
quantification detection
---------------------------------------------------------------------------------------------------------
agricultural ethyl none except for gas-liquid chromato- food, crops: Anon.
crops, animal acetate oil extracts graphy with phosphorus 0.02 mg/kg (1972)
tissues, detector
beverages,
food

fruit, hexane/ aluminium thin-layer chromato- Wood &
vegetables acetone oxide column graphy; nitrobenzyl- Kanagasa-
pyridine/triaza un- bapathy
decamethylene diamine (1983)

organs/ ethanol none thin-layer chromato- 0.2 ng Ackerman
tissues; graphy enzymatic et al.
contents of none or none assay (beef liver) (1969)
stomach, chloroform
intestines;
urine

milk, dichloro- silica gel gas chromatography 95% 0.003 mg/kg Ivey &
methane column, mixed with flame photo- Claborn
solvents metric detector (1969)

fat, hexane 80% 0.002 mg/kg Ivey &
chicken, Claborn
skin (1969)

muscle, acetonitrile silica gel 80% 0.002 mg/kg Ivey &
eggs column Claborn
(1969)
animal depending on only for fat gas-liquid chromato- 0.05 - 0.1 Schultz
tissues^a sample tissues graphy with phosphorus mg/kg et al.
and fluids detector (1971)

milk silica gel col- polarography 85% 0.15 mg/kg Davidek
umn; alkaline et al.
condensation (1976)
with o -phenyl-
enediamine
---------------------------------------------------------------------------------------------------------
^a Methods for analysing residues of four metabolites of dichlorvos are also given.

Table 4. Analytical methods for determining the dichlorvos concentration and ChE activity in blood
---------------------------------------------------------------------------------------------------------
Sample Extraction Clean-up Detection and Recovery Limit of Reference
quantification detection
---------------------------------------------------------------------------------------------------------
Dichlorvos concentrations
blood acetonitrile gas chromatography 86% Ivey & Claborn
hexane with flame photo- (1969)
metric detector

blood/serum chloroform none thin-layer chromato- Ackerman et al.
graphy enzymatic (1969)
assay (beef liver)

blood^a water/ethanol none gas-liquid chromato- Schultz et al.
extracted with graphy with phosphorus (1971);
ethyl acetate detector Anon. (1972)

ChE activity
blood electrometric method Michel (1949)
(plasma and for ChE activity,
red cell) release of acetic
acid from ACh; pH change

whole blood ACh-perchlorate tintometric method Edson (1958)
ChE and bromothymol blue

whole blood dithiobis-nitro- colorimetry at Voss & Sachsse
and plasma benzoic acid (DTNB) 420 nm (1970)
ChE + acetylthiocholine
(animal blood) or
propionyl thiocholine
(human blood);
eserine salicylate
(esterase inhibitor)

whole blood DTNB + acetylthio- spectrophotometry Ellman et al.
and erythro- choline iodide at 412 nm (1961); Anderson
cyte ChE et al. (1978)

whole blood dithiodipyridine spectrophotometry Augustinsson et
and erythro- (DTPD) + propionyl at 324 nm al. (1978)
cyte ChE thiocholine; esterase
inhibitor
---------------------------------------------------------------------------------------------------------
^a Methods for analysing concentrations of four metabolites of dichlorvos are also given.

Table 5. Analytical methods for the determination of dichlorvos in air, soil, and water
---------------------------------------------------------------------------------------------------------
Sample Extraction Clean-up Detection and Recovery Limit of Reference
quantification detection
---------------------------------------------------------------------------------------------------------
Air
glass tubes containing:
water electrometric pH Elgar & Steer
method (1972)

ethyl none gas-liquid chromato- 0.01 mg/m³ Anon. (1972)
acetate graphy with phosphorus
detector

potassium elution with gas chromatography 80% Bryant &
nitrate hexane with flame photo- Minett
metric detector (1978)

XAD-2 (per- desorption with gas chromatography 0.2 µg NIOSH
sonal samp- toluene with flame photo- (1979);
ling) metric phosphorus Gunderson
detector (1981)

Soil
soil acetone column thin-layer chromato- 1 - 2 ng Ambrus
chromatography graphy enzymatic et al.
assay (horse serum) (1981)

soil without clean- thin-layer chromato- 100 ng Ambrus
up graphy; silver et al.
nitrate + UV (1981)

soil ether/acetone flame photometric 91% 5 µg Goto
(7:3) detector-gas (1977)
petroleum ether chromatography

Water
water dichloro- column thin-layer chromato- 1 - 2 ng Ambrus
methane chromato- graphy enzymatic et al.
graphy assay (horse serum) (1981)

Table 5 (contd.)
-------------------------------------------------------------------------------------------------------------------------
Sample Extraction Clean-up Detection and Recovery Limit of Reference
quantification detection
-------------------------------------------------------------------------------------------------------------------------

without clean- thin-layer chromato- 100 ng
up graphy; silver
nitrate + UV

gas-liquid chromato- 55 - 70% 0.01 - 0.05 ng;
graphy with electron
capture detector or
thermionic ionization 0.1 - 1 ng
detector typical limit of
detection 0.0001
mg/kg
-------------------------------------------------------------------------------------------------------------------------
2.4.1 Sampling methods

2.4.1.1 Food and feed

The "Codex Recommended Method of Sampling for the Determination of
Pesticide Residues" (Codex Alimentarius Commission, 1979; GIFAP, 1982)
describes sampling rates and acceptance criteria in relation to the
analytical sample and the Codex maximum residue limits (Codex
Alimentarius Commission, 1983).

2.4.1.2 Blood

Where samples cannot be determined immediately, e.g., samples taken
in the field, they must be frozen in order to prevent the reactivation
of inhibited plasma ChE or erythrocyte AChE. When freezing facilities
are limited, or where samples must be transported and/or stored for
several days, samples of whole blood are applied to filter paper.
These samples can be stored at room temperature for at least 2 weeks
and in a refrigerator for more than 6 weeks without reducing the
efficiency of elution from the filter paper (Eriksson & Fayersson,
1980).

2.4.1.3 Air

Methods of sampling air for pesticides have been reviewed by Miles
et al. (1970), Van Dijk & Visweswariah (1975), Lewis (1976), and Thomas
& Nishioka (1985).

Miles et al. (1970) compared the widely-used techniques and came to
the conclusion that, although each method has certain advantages, none
are ideal. Packed adsorption columns are very efficient for trapping
vapours, but recovery of the sample is frequently difficult. Glass
fibre filters or cellulose filter pads permit the collection of large
volumes of air in short periods of time, but their efficiency for
vapours is low, and unknown losses of aerosol samples occur. Membrane
filters are good for liquid aerosols and vapours, but the sampling rate
is slow. However, Tessari & Spencer (1971) considered collection on a
moist nylon net to be the best sampling method for aerosol and vapour-
phase pesticides. Freeze-out traps are of limited value in field work.
Impingers seem to offer a compromise; they can be operated at quite a
fast flow rate, they are efficient for collection of aerosols, and,
with correct solvent selection, they collect vapours efficiently.

Heuser & Scudamore (1966) used dry potassium nitrate in an adsorp-
tion tube and were able to measure less than 1 µg/m³ of dichlorvos
in air.

When Miles et al. (1970) used two Greenburg-Smith-type impingers
containing water, they trapped up to 97% of dichlorvos. However, when
ethylacetate was used instead of water, more than 95% of the available
dichlorvos was collected in the first impinger (Anon., 1972).

For personal sampling of dichlorvos in the work environment,
Gunderson (1981) collected air samples from the worker's breathing zone
in glass tubes packed with XAD-2 (a styrene-divinyl benzene cross-
linked porous polymer) as sorbent. A calibrated personal sampling pump
drew air through the filter.

2.4.2 Analytical methods

2.4.2.1 Analysis of technical and formulated dichlorvos products

Dichlorvos products can be analysed by gas-liquid chromatography,
infrared spectrometry (Oba & Kawabata, 1962), or by reaction with an
excess of iodine which is estimated by titration (CIPAC Handbook,
1980). A colorimetric method to estimate dichlorvos in formulations
was described by Mitsui et al. (1963) and improved by Ogata et al.
(1975). Formulated dichlorvos can be analysed by gas-liquid
chromatography after extraction or dilution with chloroform, or after
partitioning of the dichlorvos into acetonitrile (Anon., 1972). Heuser
& Scudamore (1975) described a method to assess the output of
dichlorvos slow-release strips for insect control. A method for the
analysis of dichlorvos in technical and formulated products was
reported in WHO (1985).

Qualitative methods to identify dichlorvos or to separate and
estimate it in the presence of other organophosphorus compounds were
described by Sera et al. (1959) and Yamashita (1961).

2.4.2.2 Determination of dichlorvos residues

The main methods for determining dichlorvos are:

(a) thin-layer chromatography (TLC);

(b) enzyme-inhibition detection, coupled with TLC;

(d) GC with flame photometric detector (FPD) (the most widely-used
method for the determination of organophosphorus compounds);

(e) GC with thermionic alkaline flame ionization detector (TID),
which is more sensitive to phosphorous-containing compounds
than the FPD, but is less stable (Lewis, 1976).

Mendoza (1974) reviewed the applications of the TLC-enzyme-
inhibition technique for pesticide residues and metabolite analyses
involving determination and confirmation of pesticides.

IUPAC's Commission on Pesticide Chemistry examined simplified
analytical methods for screening pesticide residues and their
metabolites in food and environmental samples (Batora et al., 1981).

The Codex Committee on Pesticide Residues lists recommended methods
for the analysis of dichlorvos (FAO/WHO, 1986).

2.4.2.3 Confirmatory tests

Confirmation of the identity of the residue by an independent test
is an essential part of good laboratory practice. The ultimate choice
of a confirmatory test depends on the technique used in the initial
determination and on the available instrumentation and necessary
expertise. Details of various confirmatory tests have been published
(Mendoza & Shields, 1971; Shalik et al., 1971; Mestres et al., 1977;
Cochrane, 1979).

2.4.2.4 Food

The Working Group on Methods of Analysis of the Codex Committee on
Pesticide Residues has produced guidelines on good analytical practice
in residue analysis and Recommendations of Methods of Analysis for
Pesticide Residues (Codex Alimentarius Commission, 1983). The
recommended methods are mostly multiresidue ones and are suitable for
analysing as many pesticide product combinations as possible up to the
Codex maximum residue limits. The methods are summarized in Table 2.
Other methods for residue analysis are given in Table 3.

2.4.2.5 Blood

Methods for analysing dichlorvos concentrations in blood are given
in Table 4. The determination of the four metabolites of dichlorvos
was described by Schultz et al. (1971).

The most frequently used method for determining ChE activity in
blood is that of Ellman et al. (1961), subsequently modified by Voss &
Sachsse (1970) and Augustinsson et al. (1978). An improvement of this
spectrophotometric method for determining ChE activity in erythrocytes
and tissue homogenates was described by Anderson et al. (1978). The
method of Ellman et al. (1961) has been developed by WHO (1970) into a
field kit for the determination of blood ChE activity.

2.4.2.6 Air

A review of the analysis of airborne pesticides has been published
by Lewis (1976). Methods for determining dichlorvos concentrations in
air are given in Table 5.

2.4.2.7 Soil and water

Methods are summarized in Table 5.

3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1 Natural Occurrence

Dichlorvos does not occur as a natural product.

3.2 Man-Made Sources

3.2.1 Production levels and processes

3.2.1.1 Worldwide production figures

Dichlorvos has been manufactured commercially since 1961 in many
countries. Worldwide production figures for 1984 are given in Table 6.

Table 6. The worldwide production of dichlorvos in 1984
----------------------------------------------------------------------------
Country Production in tonnes
----------------------------------------------------------------------------
Eastern Europe 220

Japan 1100

Latin America 400

Middle East 1200
(including India and Pakistan)

South-East Asia 500

USA 500

Western Europe 300

Total 4220
-----------------------------------------------------------------------------

Of this total production, 60% is used in plant protection, 30% for
public hygiene and vector control, and 10% to protect stored products
(GIFAP, personal communication, 1986).

3.2.1.2 Manufacturing processes

Dichlorvos can be manufactured by the dehydrochlorination of
trichlorphon (chlorophos) through the action of caustic alkalis in
aqueous solution at 40 - 50 °C.

O O
|| ||
(CH₃O)₂PCH(OH)CCl₃ + KOH -> (CH₃O)₂POCH=CCl₂ + KCl + H₂O

The yield of dichlorvos in this process does not exceed 60%.

Another process is the reaction of chloral with trimethyl-
phosphite:
O
||
(CH₃O)₃P + CCl₃CHO -> (CH₃O)₂POCH=CCl₂ + CH₃Cl

Using this method, dichlorvos of 92 - 93% purity can be produced by
either a batch or a continuous process (Melnikov, 1971).

3.2.2 Uses

Dichlorvos is a contact and stomach insecticide with fumigant and
penetrant action. It is used for the protection of stored products and
crops (mainly greenhouse crops), and for the control of internal and
external parasites in livestock and insects in buildings, aircraft, and
outdoor areas.

As a household and public health insecticide with fumigant action,
dichlorvos has widespread use in the form of aerosol or liquid sprays,
or as impregnated cellulosic, ceramic, or resin strips, especially
against flies and mosquitos. For the control of fleas and ticks on
livestock and domestic animals (pets), impregnated resin collars are
used. A granular form of an impregnated resin strip is in use as an
anthelmintic in domestic animals.

The various formulations include emulsifiable and oil-soluble
concentrates, ready-for-use liquids, aerosols, granules, and
impregnated strips. Formulations containing mixtures of dichlorvos
with other insecticides, such as pyrethrins/piperonylbutoxide,
tetramethrin, allethrins, chlorpyriphos, diazinon, propoxur, or
fenitrothion, are also on the market.

3.2.3 Accidental release

Accidental spillages of dichlorvos could cause acute effects in
water (e.g., mortality of aquatic species), but long-term effects are
unlikely in view of its volatility and instability in humid
environments.

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

4.1 Transport and Distribution Between Media

Dichlorvos is not generally used for direct application on soil or
to water. However, in intensive fish farming, dichlorvos is added
directly to water. Any residues in soil resulting from the treatment
of crops will be small and short-lived, due to volatilization and
degradation. Therefore, contamination of ground water or surface water
is unlikely to occur in normal practice. In air, dichlorvos is rapidly
degraded, the rate depending on the humidity of the air.

4.2 Biotransformation

4.2.1 Abiotic degradation

In water, dichlorvos hydrolyses into dimethylphosphoric acid and
DCA.

The photochemical degradation rate constant at environmentally
important wavelengths (around 300 nm) was 265 x 10^-7/s at a
concentration of 0.67 µg dichlorvos/cm² of glass plate, and the half-
life was 7 h (Chen et al., 1984).

The relative persistence of dichlorvos on concrete, glass, and wood
was investigated in the laboratory. The fastest loss occurred when it
was applied to concrete; after 1 h, only 0.7% of the applied amount was
present. This rapid loss was almost certainly due to alkaline
decomposition. The disappearance rate on glass was less rapid, with a
recovery of 1% dichlorvos 3 days after application. On wood,
dichlorvos showed the greatest persistence; 65% and 39% of the applied
dichlorvos still remained after one and 33 days, respectively (Hussey &
Hughes, 1964).

When houses were treated for pest control with a total of 230-330 g
dichlorvos as aerosol and 4 - 50 g as emulsion spray, the mean
dichlorvos residue on the surface was 24 µg/100 cm² at the end of the
first day, and fell to 6 µg/100 cm² by the end of 5 days (Das et al.,
1983).

4.2.2 Biodegradation

Two ponds containing 9200 and 25 000 µg plankton/litre water,
respectively, were treated with dichlorvos by spraying under the
surface of the water. The initial dichlorvos concentration in the
water was 325 µg/litre and the half-lives were 34 and 24 h,
respectively (Grahl, 1979).

The biodegradation of dichlorvos in soil was tested in the
laboratory using moist loam. The percentages of the applied amount
(200 mg/kg soil) remaining in the soil after 1, 2, and 3 days were 93%,
62%, and 37%, respectively. Concentrations of free DCA in the soil
were 9%, 7%, and 4%, respectively (Hussey & Hughes, 1964).

In studies on the fate of dichlorvos in soil, it was shown
that Bacillus cereus grown on a nutrient medium containing 1000 mg
dichlorvos/litre could use this compound as a sole carbon source but
not as a sole phosphorus source. When soil columns were perfused with
an aqueous solution containing 1000 mg dichlorvos/litre, the metabolic
activity of B. cereus accounted for 30% of the loss of dichlorvos from
the system over a 10-day period (Lamoreaux & Newland, 1978).

Dichlorvos in concentrations ranging from 0.1 to 100 mg/litre had
little or no toxicity, as measured by the oxygen depletion caused by
microorganisms degrading organic matter in sewage (Lieberman &
Alexander, 1981, 1983).

Dichlorvos was converted to dichloroethanol, dichloroacetic acid,
and ethyldichloroacetate by a microbial enrichment derived from sewage
containing, principally, two species of Pseudomonas and one
of Bacillus. The compounds were not formed in the absence of microbial
cells. Inorganic phosphate was also generated in the presence of
microorganisms, and dimethylphosphate was produced in the presence or
absence of microbial cells (Lieberman & Alexander, 1981, 1983).

Pseudomonas melophthora, the bacterial symbiont of the apple
maggot (Rhagoletis pomonella), degraded dichlorvos mainly into water-
soluble metabolites, using esterases (Boush & Matsumura, 1967). In
addition, a strain of Trichoderma viride, a fungus isolated from soil,
has the ability to degrade dichlorvos to water-soluble metabolites,
probably through an oxidative pathway (Matsumura & Boush, 1968).

Dichlorvos is rapidly lost from leaf surfaces by volatilization and
by hydrolysis, the half-life under laboratory conditions being of the
order of a few hours. A small percentage of the dichlorvos deposited
appears to penetrate into the waxy layers of plant tissues, where it
persists longer and undergoes hydrolysis to DCA (FAO/WHO, 1968a,
1971a).

4.2.3 Bioaccumulation and biomagnification

Due to the transient nature of dichlorvos, no bioaccumulation or
biomagnification occur in soil, water, plants, vertebrates, or
invertebrates.

4.3 Ultimate Fate Following Use

Direct application of dichlorvos on crops or animals will result in
residues disappearing rapidly by volatilization and hydrolysis.
Airborne dichlorvos arising from fogging, spraying, or volatilization
from impregnated strips is hydrolysed in the atmosphere to
dimethylphosphate and DCA. Losses occur through ventilation and by
absorption and hydrolysis on surfaces. Depending on the material,
dichlorvos may be absorbed and diffuse into the material, or it may be
hydrolysed on the surface.

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1 Environmental Levels

The occurrence of dichlorvos residues in the environment does not
necessarily originate from the use of dichlorvos. It can also occur as
a conversion product of trichlorphon (Miyamoto, 1959) and butonate
(Dedek et al., 1979).

5.1.1 Air

Examples of indoor air concentrations resulting from the household
and public health use of dichlorvos are given in Table 7. The air
concentration varies according to the method of application (strips,
spray cans, or fogging), the temperature, and humidity (Gillett et al.,
1972). Using strips (one strip per 30 m³), the concentration in the
first week is in the range 0.1 - 0.3 mg/m³, depending on the
ventilation. During succeeding weeks, the concentration decreases to
about 0.04 mg/m³ and after 3 months to 0.01 mg/m³ (Elgar & Steer,
1972).

5.1.2 Food

Data on residues in food commodities resulting from pre- or post-
harvest treatment and from use on animals have been summarized by
FAO/WHO (1967a, 1968a, 1971a, 1975a). Maximum residue limits, varying
from 0.02 to 5 mg/kg, have been recommended for a range of
commodities.

Frank et al. (1983) analysed 260 bovine and porcine fat samples
collected in the period 1973-81 in Ontario. Only one sample contained
a trace of dichlorvos.

Dichlorvos residues present in food commodities are readily
destroyed during processing, e.g., washing, cooking. Hence, the chance
that dichlorvos will occur in prepared meals is very low. This was
confirmed by Abbott et al. (1970) in a total-diet study in the United
Kingdom, in which no residues of dichlorvos were detected in the 462
sub-samples analysed.

In total-diet studies (including infant and toddler diets) carried
out from 1964 to 1979 by the US Food and Drug Administration, no
dichlorvos was found (Johnson et al., 1981a,b; Podrebarac, 1984).

Food samples, meals, and unwrapped ready-to-eat foodstuffs exposed
under practical conditions to dichlorvos generated by resin strips
showed mean residues of less than 0.05 mg/kg, with a range of < 0.01 -
0.1 mg/kg (Elgar et al., 1972a,b; Collins & de Vries, 1973). No
residues of DCA (< 0.03 mg/kg; limit of detection) were detected in the
ready-to-eat foodstuffs (Elgar et al., 1972b). Food and beverages
exposed to experimental air concentrations of 0.04 - 0.58 mg/m³ for
30 min contained dichlorvos residues of 0.005 - 0.5 mg/kg, with the
exception of margarine which contained up to 1.6 mg/kg (Dale et al.,
1973).

Table 7. Indoor air concentrations of dichlorvos following various applications
---------------------------------------------------------------------------------------------------------
Location Application Dose^a Temper- RH^b Ventilation Time after Concentration Reference
ature (%) application (mg/m³)
(°C)
---------------------------------------------------------------------------------------------------------
food shops resin strip 1 strip/ normal first week 0.03 Elgar et al.
30 m³ 4 weeks 0.02 (1972b)

houses resin strip 1 strip/ 18-35 20-60 normal first week 0.06 - 0.17 Leary et al.
30 m³ 2 - 3 weeks 0.01 (1974); Elgar
& Steer (1972);
Collins & de
Vries (1973)

hospital resin strip 1 strip/ 20-27 35-70 varied several days 0.10 - 0.28 Cavagna et al.
wards 30 m³ 20 - 30 days 0.02 (1969)

hospital strips of paper 0.2 ml - - 2 h 3 days 0.06 Schulze (1979)
wards drenched in 50% ai/m³
dichlorvos sol- 0.2 ml 17 - 2 h 66 h 0.1 - 0.3
ution hanging ai/m³
in the room for 0.2 ml 17 2 h 90 h 0.3
24 - 36 h ai/m³
0.8 ml 30 high 2 h 3 h 3.7
ai/m³ 46 h 0.6

houses 0.5% solution 225 or 26 47-60 none 0 0.4 Neuwirth & White
according to 1200 ml 8 h 0.2 (1961)
typical pest 24 h < 0.1
control practice

bathroom 0.5% solution 25 ml 26 60 none 0 1.1 Neuwirth & White
(sealed) wall spray 4 h 0.3 (1961)
24 h < 0.1

Table 7 (contd.)
----------------------------------------------------------------------------------------------------------------------------------
Location Application Dose^a Temper- RH^b Ventilation Time after Concentration Reference
ature (%) application (mg/m³)
(°C)
----------------------------------------------------------------------------------------------------------------------------------
living room spray cans 2.3 mg 20-22 30 min 0 0.24 Sagner &
(experimental) ai/m³ 1 h 0 0.13 Schöndube (1982)

fogging 240 mg 20-22 none 1 h 37 Sagner &
ai/m³ none 24 h 5.5 Schöndube (1982)
1 h 1 h 2.5
120 h 1 h < 0.2

apartments 0.5% solution 190 mg 26 82 0 - 2 h 0.5 Gold et al.
ai/m² 2 - 24 h 0.2 (1984)
---------------------------------------------------------------------------------------------------------
^a ai = active ingredient.
^b RH = relative humidity.
5.2 General Population Exposure

Exposure of the general population to dichlorvos via air, water, or
food, as a result of its agricultural or post-harvest use, is
negligible. However, the household and public health use of
dichlorvos is a source of exposure. The dichlorvos slow-release resin
strip leads to exposure principally through inhalation from the air,
but dermal absorption by contact with surfaces and oral ingestion of
exposed food may also occur. Professional pest control with dichlorvos
in buildings results in the same routes of exposure but to lower levels
and for a shorter period (section 5.1).

Other sources of exposure are the use of household sprays and pet
collars.

The increased use of organophosphorus insecticide on lawns and turf
within parks and recreational areas presents a risk to human beings and
animals. They may be potentially exposed to toxic levels of residues,
although most product labels recommend that pets and children be kept
off treated turf until the spray has dried. To safeguard against
potential hazards, safe levels of dislodgeable residue have been
estimated so that safe reentry intervals or reentry precautions can be
established. In California, the estimated safe level of dislodgeable
foliar dichlorvos residue is 0.06 µg/cm².

In studies carried out by Goh et al. (1986a,b), the dislodgeable
foliar dichlorvos residue level immediately after application dropped
rapidly during the first 2 - 6 h, and after 24 - 48 h, the residue was
undetectable.

5.3. Occupational Exposure During Manufacture, Formulation, or Use

5.3.1 Air

Employees in a vaporizer production plant and adjoining packing
rooms were exposed, on average, to 0.7 mg/m³ air. The highest single
value recorded was 3 mg/m³ (Menz et al., 1974).

When air was analysed by Wright & Leidy (1980) in office and
insecticide storage rooms in commercial pest control buildings
and in vehicles, the concentrations of dichlorvos did not exceed
0.001 mg/m³ air.

Gillenwater et al. (1971) measured maximum values of 2.4 -
7 mg/m³ of dichlorvos in a large warehouse during weekly 6-h
application periods. The amounts of dichlorvos dispersed per
application ranged from 25 to 59 mg/m³ and the average air
concentration after 8 applications was 4 mg/m³.

When the floors of a mushroom house were treated with a 10%
solution of a 50% (w/v) dichlorvos emulsion (2 g dichlorvos/m³ of
house volume), air concentrations of dichlorvos were well below
1 mg/m³. The air concentrations of DCA were approximately 1
mg/m³, decreasing over 14 days to 0.3 mg/m³ (Hussey & Hughes, 1964).

During thermal fogging by swingfog of 6 greenhouses (0.2 ml
dichlorvos/m³), the workplace concentration was 7 - 24 mg/m³ (mean:
16 mg/m³). Spraying of 12 glass and plastic green-
houses resulted in workplace concentrations between 0.7 and
2.7 mg/m³ (mean:1.3 mg/m³). Field application by spraying
resulted in air concentrations of 0.01 - 0.26 mg/m³ (mean :
0.08 mg/m³) (Wagner & Hoyer, 1975, 1976).

In a tobacco-drying unit used for mushroom production, dichlorvos
was sprayed at 8 ml ai^a/100 m³, and the unit was kept closed for 24
h. Air concentrations decreased from 3.3 mg/m³ to 0.006 mg/m³ in 24
h. Treatment of the unit with paper strips drenched in 50% dichlorvos
formulation (40 ml/100 m³) resulted in air concentrations of 0.38 and
0.024 mg/m³, 3 and 24 h, respectively, after treatment (Grübner,
1972).

Immediately after spraying plants in greenhouses with a 0.2 - 0.3%
dichlorvos solution, the air concentration was 1.2 mg/m³, decreasing
to 0.01 mg/m³ 24 h later. When the plants were "shaken", air
concentrations increased by 10 - 26% (Zotov et al., 1977).

The air levels of dichlorvos in a room of a residence were moni-
tored during and after treatment with a pressurized home-fogger con-
tainer. The study was performed to determine if the prescribed 30 min
aeration period was sufficient to allow safe re-entry into a home or
room. The air levels were below the industrial workplace permissible
exposure level (PEL) of 1 mg/m³, recommended by US OSHA, at the end
of the aeration period. The dichlorvos dissipated quite slowly after
that. Without ventilation, it took 18 h to reach an acceptable level.
Because there is concern that infants and elderly or diseased persons
occupying rooms almost 24 h/day, 7 days per week, might be more
susceptible, the acceptable level for homes has been established at
1/40 of the PEL. Consequently, rooms treated with this type of
application device and ventilated after treatment should not be re-
entered for 10 h (Maddy et al., 1981a).

Dichlorvos is used to control Phorid flies in mushroom-growing
houses. After its use in one of these houses in Ventura County in the
USA in 1981, some workers complained of headaches and nausea upon re-
entry after 30 min of ventilation. Monitoring of the mushroom houses,
after the same treatment, revealed air concentrations of less than 0.1
mg/m³ (0.01 ppm). Swab samples of exposed horizontal surfaces
revealed a maximum of 0.026 µg/cm² (Maddy et al., 1981b).

-----------------------------------------------------------------------
^a ai = active ingredient.

6. KINETICS AND METABOLISM

6.1 Absorption

Dichlorvos is readily absorbed via all routes of exposure. In the
rat, dichlorvos taken orally is absorbed by the gastrointestinal tract,
transported via the hepatic portal venous system to the liver, and
detoxified before it reaches the systemic circulation (Gaines et al.,
1966; Laws, 1966).

Air exhaled by anaesthetized and tracheotomized pigs exposed by
inhalation to dichlorvos for up to 6 h revealed that, at dichlorvos
concentrations of 0.1 - 2 mg/m³, the pigs retained 15 - 70% of the
inhaled dichlorvos (Kirkland, 1971).

The percutaneous absorption of undiluted dichlorvos and solutions
of dichlorvos applied (under a glass cover slip) to rabbit skin was
calculated from the slope of the whole blood ChE activity inhibition
curve. Water and acetone solutions did not increase absorption,
whereas xylene and dimethylsulfoxide (DMSO) enhanced absorption
(Shellenberger et al., 1965; Shellenberger, 1980). The results are
summarized in Table 8.

Table 8. Effect of solvent on whole blood ChE activities and absorption
rates^a after percutaneous application of dichlorvos to rabbit skin
-----------------------------------------------------------------------------
Solvent ChE inhibition Time after Absorption
(%) application (mg/min per cm²)
-----------------------------------------------------------------------------
0.5 ml undiluted 30 2 h 3.8
dichlorvos

+0.5 ml acetone 45 2 h 4.08

+0.5 ml water 45 2 h 4.29

+0.5 ml xylene 100 40 min 11.96

+0.5 ml DMSO 100 35 min 16.08
-----------------------------------------------------------------------------
^a Calculated from the slope of the enzyme inhibition curve.

6.1.1 Human studies

Dichlorvos was undetectable (less than 0.1 mg/litre) in the blood
of two men immediately after exposure, one to air concentrations of
0.25 mg dichlorvos/m³ for 10 h and one to 0.7 mg dichlorvos/m³ for
20 h (Blair et al., 1975).

6.2 Distribution

6.2.1 Studies on experimental animals

6.2.1.1 Oral

³²P-Dichlorvos administered orally to rats at a single dose of
10 mg/kg body weight was found to be readily absorbed, distributed
among the tissues, hydrolysed, and rapidly metabolized. Radioactivity
was detected in the blood 15 min after administration, and the amount
slowly decreased over subsequent days. The concentrations of ³²P in
kidneys, liver, stomach, and intestines reached their maximum 1 h after
dosing, and decreased within 1 day. The concentration in bone
increased slowly with time due to the ³²P entering the inorganic
phosphate pool of the organism. No sex differences were found (Casida
et al., 1962).

When 1 mg of ¹⁴C-methyldichlorvos was administered orally to
rats, the gut, skin, and carcass contained 0.7%, 1.6%, and 5.2%,
respectively, of the administered radioactivity, 4 days after dosing
(Hutson & Hoadley, 1972b). In an earlier study on rats dosed orally
with 1 mg vinyl-1-¹⁴C-dichlorvos, the gut, skin, and carcass
contained 1.7%, 7.5%, and 14%, respectively, of the ¹⁴C, 4 days after
dosing (Hutson et al., 1971a,b).

Twenty-four hours after the administration of a single oral dose of
0.2 mg vinyl-1-¹⁴C-dichlorvos to mice, 26 - 34% of the radioactivity
was found in the carcass (Hutson & Hoadley, 1972a). Syrian hamsters
dosed with vinyl-1-¹⁴C-dichlorvos retained similar percentages in the
gut, skin, and carcass as did rats (Hutson & Hoadley, 1972a).

Fetuses from rabbits treated with daily oral doses of 5 mg
dichlorvos/kg body weight for 25 days of gestation were found to
contain no dichlorvos (Majewski et al., 1979).

In studies by Potter et al. (1973a), nine pigs received a single
oral dose of vinyl-1-¹⁴C-dichlorvos (approximately 40 mg
dichlorvos/kg feed) formulated as slow-release PVC pellets.
Sacrifices after 2, 7, and 14 days showed that all the tissues
contained ¹⁴C. The highest level of radioactivity, expressed as
dichlorvos equivalent, was found in liver tissue after 2 days
(33 mg/kg) and the lowest in brain tissue (2.5 mg/kg). In another
study, pregnant sows were fed vinyl-1-¹⁴C-dichlorvos or
³⁶Cl-dichlorvos in PVC pellets at 4 mg dichlorvos/kg body weight per
day for the last third of the sow's gestation period. After farrowing,
the sows and piglets, nursing from their own mothers, were kept for 21
days before being sacrificed. The tissues of the sows and piglets
contained ¹⁴C and ³⁶Cl residues ranging from 0.3 to 18 mg/kg tissue
equivalents. In neither study, were residues of dichlorvos, DCA,
desmethyldichlorvos, dichloroacetic acid, or dichloroethanol found in
the tissues (Potter et al., 1973a,b).

No dichlorvos was found in muscle (fat) tissue of rabbits treated
with daily oral doses of 5 mg dichlorvos/kg body weight for 2 weeks and
sacrificed at intervals up to 48 h after the last dose (Majewski et
al., 1979).

6.2.1.2 Inhalation

When groups of 3 rats and mice were exposed by inhalation to a
concentration of 90 mg dichlorvos/m³ air for 4 h, the rats exhibited
mild signs of intoxication (lethargy, pupillary constriction).
Concentrations of dichlorvos were very low or undetectable in blood
(< 0.2 mg/kg), liver, testes, lung, and brain (< 0.1 mg/kg), while the
kidneys and fat contained the highest concentrations (up to 2.4 and
0.4 mg/kg tissue, respectively). In rats, the values for the trachea
were higher than those for the lungs, indicating perhaps that some
dichlorvos is trapped in the trachea. When rats were exposed for 4 h
to 10 mg/m³ air, only the kidneys of the male animals contained
measurable or detectable dichlorvos concentrations (0.08 mg/kg). Mice
gave different results from rats, having higher concentrations of
dichlorvos in fat, lung, and testes, and much lower concentrations in
the kidneys. Exposure of male rats to 0.5 or 0.05 mg/m³ for 14 days
did not result in detectable residues (< 0.001 mg/kg) of dichlorvos in
blood, liver, kidneys, renal fat, or lung tissue. However, in male
rats exposed to approximately 50 mg dichlorvos/m³, dichlorvos (1.7
mg/kg) was found in the kidneys after 2 and 4 h exposure time. On
removal of the rats from the test atmosphere, the dichlorvos rapidly
disappeared from the kidneys, with a half-life of 13.5 min. The rate
of disappearance of dichlorvos in the blood was too rapid to measure;
it could not be detected 15 min after exposure (Blair et al., 1975).

Short-term inhalation trials in anaesthesized pigs did not
show the presence of intact dichlorvos or desmethyldichlorvos in
blood or lung tissues. Even in the 2- to 4-h trials, the
degradation proceeded to the stage where only methylphosphates and
phosphoric acid could be detected (Loeffler et al., 1971). When young
swine were exposed for 24 h to an atmosphere containing about 0.15 mg
vinyl-1-¹⁴C-dichlorvos/m³, the ¹⁴C content varied widely among the
different tissues, but none contained dichlorvos (Loeffler et al.,
1976).

6.2.1.3 Intraperitoneal

Nordgren et al. (1978) showed that within 1 min after a single
intraperitoneal injection of 10 mg dichlorvos/kg body weight to mice,
dichlorvos was detectable in the brain, but its concentration decreased
within a few minutes.

Mice and rats treated repeatedly by intraperitoneal injection with
10 or 4 mg ³²P-dichlorvos/kg body weight showed hydrolysis products in
the tissues within 2 h (Casida et al., 1962). When male rats were
injected intraperitoneally with vinyl-1-¹⁴C-dichlorvos, the mean 24-h
retention percentages of administered radioactivity were: gut, 4%;
skin, 7%; and carcass, 23% (Hutson et al., 1971b). No differences in
the amount or distribution of radioactivity in the tissues of female
rats given either a single oral or intraperitoneal dose of 4 mg vinyl-
1-¹⁴C-dichlorvos/kg body weight were reported (Casida et al., 1962).

6.2.1.4 Intravenous

The dichlorvos concentrations in the kidneys of three male rats, 10
and 30 min after a single intravenous injection, showed a considerable
decrease, suggesting rapid metabolism of dichlorvos. As was the case
after oral administration, dichlorvos could not be detected in the
kidneys of female rats (Blair et al., 1975).

6.3 Metabolic Transformation

Early in vitro and in vivo studies indicated that detoxification of
dichlorvos occurs in the liver (Casida et al., 1962; Hodgson & Casida,
1962; Gaines et al., 1966; Laws, 1966). In vitro studies have shown
that rat liver degrades dichlorvos by two main enzymatic pathways, one
being glutathione dependent and producing desmethyldichlorvos, and the
other being glutathione independent and resulting in dimethylphosphate
and DCA. The degradation of desmethyldichlorvos to DCA and
monomethylphosphate was also found to be glutathione independent
(Dicowsky & Morello, 1971). Sakai & Matsumura (1971) demonstrated
the in vitro degradation of dichlorvos by human brain esterases.

Hodges & Casida (1962) have found that dichlorvos is hydrolysed by
the soluble and mitochondrial fractions of the rat liver but not by the
microsomes. DCA is reduced in the presence of NADH to dichloroethanol
and possibly to dichloroacetate.

The rapidity of dichlorvos metabolism has been demonstrated
in in vitro studies using fresh liver tissue. Ten minutes after
mixing 1 mg dichlorvos with 1 g of liver tissue, 50% dichlorvos was
recovered; after 123 min, only 0.4% remained (Majewski et al., 1979).
However, it is not only liver tissue that metabolizes dichlorvos.
³²P-Dichlorvos was metabolized in the presence of blood and of
adrenal, kidney, lung, and spleen tissues, mainly to dimethylphosphate.
Desmethyldichlorvos, monomethylphosphate, and inorganic phosphate were
also found (Hodgson & Casida, 1962; Loeffler et al., 1971).

The identification of dichlorvos metabolites has been undertaken
in in vivo studies of mice (Casida et al., 1962; Hutson & Hoadley,
1972a,b), rats (Casida et al., 1962; Bull & Ridgeway, 1969; Hutson et
al., 1971b; Hutson & Hoadley, 1972b), Syrian hamsters (Hutson &
Hoadley, 1972a), pigs (Loeffler et al., 1971, 1976; Page et al., 1972;
Potter et al., 1973a,b), goats (Casida et al., 1962), cows (Casida et
al., 1962), and human beings (Hutson & Hoadley, 1972a), after different
routes of administration using radiolabelled dichlorvos. In general,
the metabolism of dichlorvos in the various species is similar and
rapid. Differences between species are related to the rate of
metabolite formation rather than to the nature of the metabolites.

In the mouse, O- desmethylation is a more important route of
dichlorvos detoxification than it is in the rat (Table 9), as indicated
by the larger amounts of radioactivity excreted in the mice as
desmethyldichlorvos.

Table 9. Isotope dilution analysis of urine from mammals treated orally
with vinyl-1-¹⁴C-dichlorvos^a
-----------------------------------------------------------------------------
Metabolite Proportion of administered radioactivity as
measured urinary metabolite (%)
rat mouse hamster man
----------------------------------------------------------------------------
hippuric acid 1.7 0.6 1.0 0.4
desmethyldichlorvos 2.2 18.5 -^b 0.15
urea (isolated as 0.6 0.6 -^b 0.1
the nitrate salt)
-----------------------------------------------------------------------------
^a From: Hutson & Hoadley (1972a).
^b Not measured.

Desmethyldichlorvos arises from the hydrolysis of the methyl
oxygen-phosphate bond and is further degraded into DCA, mono-
methylphosphate, and dimethylphosphate (Casida et al., 1962; Hodgson &
Casida, 1962; Bradway et al., 1977). S- methyl-glutathione is formed
along with desmethyldichlorvos, and is degraded to methylmercapturic
acid and excreted in the urine (Hutson & Hoadley, 1972b).

The two major routes of metabolism of the vinyl portion of the
dichlorvos molecule lead to: (a) dichloroethanol glucuronide, and (b)
hippuric acid, urea, carbon dioxide, and other endogenous biochemicals
which give rise to high levels of radioactivity in the tissues for a
few days after dosing with vinyl-1-¹⁴C-dichlorvos. Both pathways
have been shown to occur in man, owing to the presence of these
compounds in the urine (Hutson & Hoadley, 1972a). In laboratory
animals most of the observed radioactivity in carcasses and tissues was
present as glycine, serine, and other normal body components,
indicating that the vinyl carbon atoms of dichlorvos enter the 2-carbon
metabolic pool (Hutson et al., 1971b; Page et al., 1971; Hutson &
Hoadley, 1972b; Loeffler et al., 1976). No evidence of accumulation of
dichlorvos or potentially toxic metabolites was found. A scheme of the
metabolites of dichlorvos in mammals is given in Fig. 1.

6.3.1 Metabolites

When ³²P-dimethylphosphate (500 mg/kg body weight) was
administered orally to a male rat almost the entire dose was
eliminated. The urine contained about 50% unmetabolized
dimethylphosphate. On the other hand, a rat orally dosed with
³²P-desmethyldichlorvos (500 mg/kg body weight) eliminated about
14% of the dose via urine in 90 h, 86% of the radioactivity being
phosphoric acid and 14% unchanged desmethyldichlorvos. The very
high proportion of radioactivity in the bone was indicative of rapid
degradation to phosphoric acid (Casida et al., 1962).

Following the intraperitoneal injection of 1-¹⁴C-DCA or
1-¹⁴C-dichloroethanol to female rats, 32% of the radioactivity was
expired as carbon dioxide within 24 h (Casida et al., 1962).

6.4 Elimination and Excretion in Expired Air, Faeces, and Urine

6.4.1 Human studies

Eight hours after a human male consumed 5 mg of vinyl-1-
¹⁴C-dichlorvos in orange juice, 27% of the radioactivity had been
eliminated as ¹⁴C-carbon dioxide. Approximately 8% had been excreted
by the urine within one day following dosing. Urinary excretion of
radioactivity decreased gradually and by day 9 none was detectable
(Hutson & Hoadley, 1972a).

The concentration of dimethylphosphate in the urine of three
pesticide control operators spraying houses with dichlorvos ranged from
0.32 to 1.4 µg at the end of the day's work (Das et al., 1983).

6.4.2 Studies on experimental animals

6.4.2.1 Oral

Dosing rats orally with ³²P-dichlorvos (0.1 - 80 mg/kg body
weight) resulted in a recovery of 60 - 70% of the administered
radioactivity in the urine and approximately 10% in the faeces over a
6-day period following dosing (Casida et al., 1962).

After the oral administration of methyl-¹⁴C-dichlorvos to rats
(1 mg) and mice (0.5 mg), the excretion of radioactivity was rapid.
The major route of elimination after 4 days was the urine
(approximately 60%), followed by expired air (approximately 16%)
(Hutson & Hoadley, 1972b).

Rats given an oral dose of vinyl-1-¹⁴C-dichlorvos (1 mg per
animal) eliminated 10 - 20% of the ¹⁴C in the urine, 3 - 5% in the
faeces, and approximately 40% as expired carbon dioxide over 4 days
following dosing (Hutson et al., 1971a,b).

A comparison between the excretion by rat, mouse, hamster, and man
24 h after oral dosing with vinyl-1-¹⁴C-dichlorvos is given in
Table 10 (Hutson & Hoadley, 1972a).

A cow treated orally with 20 mg/kg body weight
³²P-dichlorvos eliminated 40% of the radioactivity in the urine and
50% in the faeces. In the milk, the level of organosoluble radio-
activity was significantly above background only within the first 2 h
(Casida et al., 1962).

Table 10. Comparison of percentages of radioactivity excreted by males
24 h after oral ingestion of vinyl-1-¹⁴C-dichlorvos^a
-----------------------------------------------------------------------------
Excretion route Rat (3) Mouse (1) Hamster (2) Man (1)
-----------------------------------------------------------------------------
urine 9.8 27.4 14.7 7.6

faeces 1.5 3.2 2.9 -

carbon dioxide 28.8 23.1 33.5 27 (8 h only)
-----------------------------------------------------------------------------
^a Number of animals are given in parentheses.

6.4.2.2 Parenteral

The elimination of a single intraperitoneal injection of vinyl-1-
¹⁴C-dichlorvos (4 mg/kg body weight) from female rats was similar to
the elimination after oral dosing. A goat treated subcutaneously with
1.5 mg ³²P-dichlorvos/kg body weight excreted 79% of the radioactivity
in the urine and 11% in the faeces. Two cows received an intravenous
or a subcutaneous injection with 1 mg ³²P-dichlorvos/kg body weight.

Of the radioactivity which was recovered, 70 - 80% was in the urine and
approximately 14% in the faeces (Casida et al., 1962).

6.5 Retention and Turnover

6.5.1 Biological half-life

In studies by Blair et al. (1975), the metabolism of dichlorvos was
found to be so rapid that the biological half-life in blood could not
be determined. No intact dichlorvos could be demonstrated in the blood
or tissues of animals exposed by routes other than parenteral
injection. Only after exposure for 4 h to an atmospheric concentration
of 90 mg dichlorvos/m³ could dichlorvos be detected in most tissues of
the rat and mouse. Following exposure at 50 mg/m³, for 2 or 4 h, the
half-life in the rat kidney was 13.5 min.

The intraperitoneal injection of 10 mg dichlorvos/kg body weight
into mice increased the accumulation of ACh in the brain and caused an
inhibition of ChE activity. Symptoms of toxicity were clearly
recognizable after 15 min, and they disappeared almost completely after
60 min. The ChE activity and ACh levels reached their minimum and
maximum, respectively, at 15 min. The maximum concentration of
dichlorvos in the brain was reached after 1 min and decreased
thereafter, rapidly reaching the baseline level after 3 min (Nordgren
et al., 1978).

6.5.2 Body burden

There is no evidence for the storage of dichlorvos or its
metabolites in the tissues of animals. Small fractions of the carbon,
phosphorus, and chlorine derived from dichlorvos are retained in the
body for several days because their turnover rate is the same as that
for identical materials from other origins.

6.5.3 Indicator media

The determination of dichloroethanol in urine as a means of
monitoring the exposure of human beings to dichlorvos is not
sufficiently sensitive to detect levels arising from vapour exposure
through normal use. However, it could serve as the basis for a
specific detection method for the accidental ingestion of high levels
(Hutson & Hoadley, 1972a). Two other methods can be used: (a)
determination of the blood ChE activity; or (b) determination of
dimethylphosphate in urine by a rather complicated method (Blair &
Roderick, 1976). Neither method is specific when exposure to other
organophosphate or carbamate compounds, or to compounds that also
metabolize to dimethylphosphate, may have occurred.

7. EFFECTS ON ORGANISMS IN THE ENVIRONMENT

7.1 Microorganisms

Lal (1982) reviewed the accumulation, metabolism, and effects of
organophosphorus insecticides on microorganisms.

Microorganisms undoubtedly have the ability to metabolize
organophosphorus insecticides; however, there are still large gaps in
our knowledge. It also seems clear that chemical, photochemical,
physical, and biological factors may influence the metabolism of
dichlorvos by microorganisms.

7.1.1 Algae and plankton

The dose of dichlorvos producing 50% growth inhibition of the
unicellular alga Euglena gracilis has been quoted as 3.5 mg/litre
(Butler, 1977).

Treating eutrophic carp ponds with 0.325 mg/litre killed
Cladocera (predominantly Bosmina and Daphnia species) and decreased
Copepoda (mainly Cyclops ). This was offset by increased development
of Rotatoria (mainly Polyarthra and Brachionus species) and
phytoplankton (mainly Scenedesmus and Pediastrum species), so that
the total plankton biomass changed only slightly (Grahl et al., 1981).

7.1.2 Fungi

Dichlorvos (in the range 10 - 80 mg/litre) has been found to affect
citric acid fermentation in Aspergillus niger grown in an artificial
medium. Inhibition of the fermentation was marked only at 40 and
80 mg/litre (Rahmatullah et al., 1978; Ali et al., 1979c). It appears
from the decreased uptake of inorganic phosphorus that dichlorvos may
have an interfering action on oxidative metabolism in A. niger. The
potential for inhibiting citrinin production by Penicillium
citrinum was investigated. Dichlorvos inhibited citrinin production by
76% at 100 µg/litre and by 48% at 10 µg/litre (Draughon & Ayres,
1978). The effect of dichlorvos on the survival time and the membrane
potential of the slime mould Physarum polycephalum was studied in a
laboratory test system. The threshold value for both these effects was
found to be 300 mg/litre for technical dichlorvos and 30 mg/litre for
the pure chemical (Terayama et al., 1978).

The influence of dichlorvos on 17 soil fungi, cultivated in
artificial medium, was tested. Dose levels of 0, 10, 30, 60, and
120 mg/kg were used during a test period of 21 days, and the effect on
the growth and morphology of the fungi was studied. In general, a
growth depression was found, but its extent depended on the fungal
strain. Occasionally growth was either unaffected