INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
ENVIRONMENTAL HEALTH CRITERIA 76
THIOCARBAMATE PESTICIDES - A GENERAL INTRODUCTION
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World Health Orgnization
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CONTENTS
ENVIRONMENTAL HEALTH CRITERIA FOR THIOCARBAMATE PESTICIDES:
A GENERAL INTRODUCTION
INTRODUCTION
1. SUMMARY
1.1. General
1.2. Properties, uses, and analytical methods
1.3. Sources, environmental transport, and distribution
1.4. Environmental levels and human exposure
1.5. Kinetics and metabolism
1.6. Effects on organisms in the environment
1.7. Effects on experimental animals and in vitro test systems
1.8. Effects on man
2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS
2.1. Identity
2.2. Physical and chemical properties
2.3. Analytical methods
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE
3.1. Natural occurrence
3.2. Man-made sources
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION
4.1. Transport and distribution between media
4.1.1. Soil
4.1.1.1 Persistence and volatilization
4.1.1.2 Leaching
4.1.1.3 Lateral movement
4.2. Biotransformation
4.2.1. Microbial degradation
4.2.2. Photodegradation
5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE
6. KINETICS AND METABOLISM
6.1. Absorption, distribution, and excretion
6.2. Metabolic transformation
6.2.1. Mammals
6.2.2. Plants
7. EFFECTS ON ORGANISMS IN THE ENVIRONMENT
7.1. Microorganisms
7.2. Aquatic organisms
7.3. Terrestrial organisms
7.3.1. Birds
7.3.2. Honey bees
8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS
8.1. Single exposures
8.2. Short- and long-term exposure
8.2.1. Experimental animals
8.2.2. Domestic animals
8.3. Skin and eye irritation; sensitization
8.4. Reproduction, embryotoxicity, and teratogenicity
8.4.1. Reproduction
8.4.2. Teratogenicity
8.5. Mutagenicity and related end-points
8.6. Carcinogenicity
9. EFFECTS ON MAN
9.1. Occupational exposure
10. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES
REFERENCES
ANNEX I NAMES AND STRUCTURES OF SELECTED THIOCARBAMATES
ANNEX II THIOCARBAMATES: JMPR REVIEWS, ADIs, EVALUATION BY IARC,
CLASSIFICATION BY HAZARD, FAO/WHO DATA SHEETS, IRPTC DATA
PROFILE AND LEGAL FILE
WHO TASK GROUP ON THIOCARBAMATE PESTICIDES
Members
Dr U.G. Ahlborg, Unit of Toxicology, National Institute of
Environmental Medicine, Stockholm, Sweden (Vice-Chairman)
Dr R.C. Dougherty, Department of Chemistry, Florida State
University, Tallahassee, Florida, USA
Dr H.H. Dieter, Federal Health Office, Institute for Water,
Soil and Air Hygiene, Berlin (West)
Dr A.H. El Sabae, Pesticide Division, Faculty of Agriculture,
University of Alexandria, Alexandria, Egypta
Dr A. Furtado Rahde, Ministry of Public Health, Porto Alegre,
Brazil (Chairman)
Dr S. Gupta, Department of Zoology, Faculty of Basic Sciences,
Punjab Agricultural University, Ludhiana, Punjab, Indiaa
Dr L.V. Martson, All Union Scientific Research Institute of the
Hygiene and Toxicology of Pesticides, Polymers, and
Plastics, Kiev, USSRa
Dr U.G. Oleru, Department of Community Health, College of Med-
icine, University of Lagos, Lagos, Nigeria
Dr Shou-Zheng Xue, Toxicology Programme, School of Public
Health, Shanghai Medical University, Shanghai, China
Observers
Dr R.F. Hertel, Fraunhöfer Institute for Toxicology and Aerosol
Research, Hanover, Federal Republic of Germany
Dr E. Kramer (European Chemical Industry Ecology and Toxico-
logy Centre), Dynamit Nobel AG, Cologne, Federal Republic of
Germany
Mr G. Ozanne (European Chemical Industry Ecology and Toxico-
logy Centre), Rhone Poulenc DSE/TOX, Neuilly-sur-Seine,
France
Mr V. Quarg, Federal Ministry for Environment, Nature Con-
servation and Nuclear Safety, Bonn, Federal Republic of
Germany
Dr U. Schlottmann, Chemical Safety, Federal Ministry for
Environment, Nature Conservation and Nuclear Safety, Bonn,
Federal Republic of Germany
Dr M. Sonneborn, Federal Health Office, Berlin (West)
Dr W. Stöber, Fraunhöfer Institute for Toxicology and Aerosol
Research, Hanover, Federal Republic of Germany
Dr D. Streelman (International Group of National Associations
of Agrochemical Manufacturers), Agricultural Chemicals
Registration and Regulatory Affairs, Rohm & Haas,
Philadelphia, Pennsylvania, USA
a Invited but unable to attend.
Secretariat
Mrs B. Bender, International Register for Potentially Toxic
Chemicals, Geneva, Switzerland
Dr A. Gilman, Industrial Chemicals and Product Safety Section,
Health Protection Branch, Department of National Health and
Welfare, Tunney's Pasture, Ottawa, Ontario, Canada
(Temporary Adviser)
Dr L. Ivanova-Chemishanska, Institute of Hygiene and Occupa-
tional Health, Medical Academy, Sofia, Bulgaria (Temporary
Adviser)
Dr K.W. Jager, International Programme on Chemical Safety,
World Health Organization, Geneva, Switzerland (Secretary)
Dr E. Johnson, Unit of Analytical Epidemiology, International
Agency for Research on Cancer, Lyons, France
Dr G. Rosner, Fraunhöfer Institute for Toxicology and Aerosol
Research, Hanover, Federal Republic of Germany (Temporary
Adviser)
Dr G.J. Van Esch, Bilthoven, Netherlands (Temporary Adviser)
(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.
ENVIRONMENTAL HEALTH CRITERIA FOR THIOCARBAMATE PESTICIDES
A WHO Task Group on Environmental Health Criteria for
Thiocarbamate Pesticides met at the Fraunhöfer Institute for
Toxicology and Aerosol Research, Hanover, Federal Republic of
Germany from 20 to 24 October, 1986. Professor W. Stöber opened
the meeting and welcomed the members on behalf of the host
Institute, and Dr U. Schlottmann spoke on behalf of the Federal
Government, who sponsored the meeting. Dr K.W. Jager addressed
the meeting on behalf of the three co-sponsoring organizations
of the IPCS (UNEP/ILO/WHO). The Task Group reviewed and revised
the draft criteria document and summarized the health risks of
exposure to thiocarbamate pesticides.
The drafts of this document were prepared by DR L. IVANOVA-
CHEMISHANSKA, Institute of Hygiene and Occupational Health,
Sofia, Bulgaria, and Dr G.J. VAN ESCH of Bilthoven,
Netherlands.
The efforts of all who helped in the preparation and
finalization of the document are gratefully acknowledged.
* * *
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.
INTRODUCTION
The thiocarbamates included in this review are those that
are mainly used in agriculture and form part of the large group
of synthetic organic pesticides that have been developed and
produced on a broad scale in the last 30 - 40 years. Thio-
carbamate derivatives with pesticidal properties were developed
during and after World War II.
In this introductory document, an attempt has been made to
summarize the available data on the thiocarbamates used as
pesticides in order to indicate their impact on man, animals,
plants, and the environment. The review is not intended to be
complete, and more details about certain aspects can be found in
the JMPR and IARC publications.
It should be noted that the design of a number of studies
cited in this document, especially the earlier studies, is
inadequate.
1. SUMMARY
1.1 General
Thiocarbamates are mainly used in agriculture as insect-
icides, herbicides, and fungicides. Additional uses are as
biocides for industrial or other commercial applications, and in
household products. Some are used for vector control in public
health.
The general formula of thiocarbamates is:
O R2
|| /
R1-S-C-N
\
R3
where R1 is an alkyl group attached to the sulfur giving S -
thiocarbamates or to the oxygen giving O-thiocarbamates. R2
and R3 represent either two alkyl groups, or one alkyl and one
cyclic or hexamethylene group.
A whole range of thiocarbamates is known, but it is out of
the scope of this publication to give all the information on
every compound. The intention is to cover the different aspects
of thiocarbamates as a group, making use of publications and
reports available on the compounds that are most used and best
known. Data on carbamates and dithiocarbamates are not
included, because these compounds have been covered in other
Environmental Health Criteria documents.
1.2 Properties, Uses, and Analytical Methods
Thiocarbamates are liquids or solids with low melting
points. They are volatile compounds, and their water
solubilities cover a wide range. Some thiocarbamates are stable
in an acidic aqueous medium. The sequential oxidation of
thiocarbamates to thiocarbamate sulfoxide and thiocarbamate
sulfone decreases the hydrolytic stability.
Some physical and chemical data (chemical structure,
relative molecular mass, vapour pressure, and water solubility)
of individual substances are given in Annex I.
Analytical methods for the determination of thiocarbamates
are outlined in the document and further details, together with
physical and chemical data, can be found in the WHO Technical
Report Series and the IRPTC data profiles.
1.3 Sources, Environmental Transport, and Distribution
Because of their insecticidal, herbicidal, and fungicidal
properties, thiocarbamates have a wide range of uses and
applications throughout the world and, thus, are produced in
great quantities.
Thiocarbamates are volatile and will therefore evaporate
from soil. Leaching and lateral movement in soil may take place
because of their water solubility. Some photodegradation
occurs.
Factors that influence the biodegradation of thiocarbamates
in soil include volatility, soil type, soil moisture,
adsorption, pH, temperature, and photodegradation, all of which
make it unlikely that long-term contamination of the soil will
occur.
Soil microorganisms contribute significantly to the
disappearance of thiocarbamates from the soil. In micro-
organisms and plants, thiocarbamates undergo hydrolysis followed
by transthiolation and sulfoxidation to form carbon dioxide
(CO2) and compounds that enter the metabolic pool.
1.4 Environmental Levels and Human Exposure
Information on the environmental impact of thiocarbamates
with respect to persistence and bioaccumulation in different
species and food chains is limited. On the basis of the
available information, it is likely that most of these compounds
are rapidly degraded.
Estimates of the exposure of the general population to
thiocarbamates are not available.
1.5 Kinetics and Metabolism
As a general rule, thiocarbamates can be absorbed by the
organism via the skin, mucous membranes, and the respiratory and
gastrointestinal tracts. They are eliminated quite rapidly,
mainly via expired air and urine.
Two major pathways exist for the metabolism of
thiocarbamates in mammals. One is via sulfoxidation and
conjugation with glutathione. The conjugation product is then
cleaved to a cysteine derivative, which is metabolized to a
mercapturic acid compound. The second route is oxidation of the
sulfur to a sulfoxide, which is then oxidized to a sulfone, or
hydroxylation to compounds that enter the carbon metabolic
pool.
In plants, thiocarbamates are rapidly metabolized in typical
oxidation reactions, e.g., thiol sulfur oxidation to the corres-
ponding sulfoxides, reactive intermediates that are capable of
reacting with sulfhydryl groups (as in glutathione, cysteine)
to form conjugates. On hydrolysis, mercaptans, carbon dioxide,
and alkylamines may be formed.
While thiocarbamates and their metabolic products can be
found in certain organs, such as liver and kidneys, accumulation
does not take place because of their rapid metabolism.
1.6 Effects on Organisms in the Environment
Soil microorganisms are capable of metabolizing
thiocarbamates. From the limited information available, it
seems that the thiocarbamates and their break-down products can
affect enzyme activities, respiration, and nitrification, at
dose levels of the order of 10 mg/kg dry soil or more.
The acute and long-term toxicities of thiocarbamates must be
considered for each compound, some being more toxic than others.
The acute toxicity of thiocarbamates for fish is of the order of
5 - 25 mg/litre of water.
Thiocarbamates present little or no risk for birds and honey
bees.
1.7 Effects on Experimental Animals and In Vitro Test Systems
The acute oral and dermal toxicities of thiocarbamates are
generally low. Only limited information concerning inhalation
toxicity is available.
Some thiocarbamates, e.g., molinate, have an effect on sperm
morphology and, consequently, on reproduction. However, no
teratogenic effects have been observed. The results of
mutagenicity studies showed that thiocarbamates containing
dichloroallyl groups were highly mutagenic. Negative results
were obtained with other thiocarbamates.
Adequate studies on the carcinogenicity of thiocarbamates
are not available.
1.8 Effects on Man
Data concerning the effects of thiocarbamates on man are
scarce. However, cases of irritation and sensitization have
been observed among agricultural workers.
2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS
2.1 Identity
Thiocarbamates are the semi-sulfur analogues of carbamates
characterized by the presence of:
O
||
-S-C-N=
They exist as salts or esters of carbamic acids. In the esters,
the alkyl substituent is either attached to the oxygen ( O-
thiocarbamates) or to the sulfur ( S- thiocarbamates).
The thiocarbamate herbicides belong to the group of S -
thiocarbamate esters and have the general formula of:
O R2
|| /
R1-S-C-N
\
R3
where R1 is an alkyl group attached to the sulfur, and R2 and R3
represent either 2 alkyl groups, or one alkyl and one cyclic or
hexamethylene group.
The type of pesticidal activity and the chemical structures
of the principle thiocarbamates are listed in Table 1. CAS
numbers, chemical names, common names, molecular formulae,
relative molecular mass, and selected chemical and physical
properties are summarized in Annex I.
For further information on physical and chemical properties,
other sources, such as the JMPR evaluations (Annex II), should
be consulted.
2.2 Physical and Chemical Properties
At room temperature, thiocarbamates are liquids or solids
with a low melting point. As they are usually N,N -dialkyl
substituted and have a sulfur atom in place of oxygen, they are
less polar than methylcarbamates and are miscible with most
organic solvents.
All thiocarbamate herbicides are volatile. Pebulate has the
highest vapour pressure, followed by S -ethyldipropylthio-
carbamate (EPTC), cycloate, molinate, butylate, diallate, and
triallate (IARC, 1976; Worthing & Walker, 1983).
Thiocarbamates such as EPTC, pebulate, or diallate are very
stable at pH 2 or 10. Their sulfoxide and sulfone derivatives
are also stable at pH 2, but much less so at pH 10 (Casida et
al., 1974).
Table 1. Chemical structures and type of pesticidal activity of the
principal thiocarbamates
------------------------------------------------------------------------
Type of Chemical structure Common or other name
activity
------------------------------------------------------------------------
Insecticide
O
|| cartap
R1-S-C-NH2
Herbicide
O R2 butylate, cycloate,
|| / diallate, EPTC,
R1-S-C-N ethiolate, molinate,
\ pebulate, thioben-
R3 carb, triallate
Fungicide
prothiocarb
O R2
|| /
R1-S-C-N
\
H
------------------------------------------------------------------------
The presence of a double bond in the chloroallyl group of
diallate and triallate might increase, compared with that of
other thiocarbamates, the possible range of reactions, e.g., the
introduction of hydroxyl groups on the two-carbon atoms or
methylation and methoxylation (Schuphan & Ebing, 1977).
2.3 Analytical Methods
Analysis for pesticide residues consists of sampling the
environmental material or matrix, extracting the pesticide
residue, removing interfering substances from the extract, and
identifying and quantifying the pesticide contaminant. The
manner in which the matrix material is sampled, stored, and
handled can affect the results. Care should be taken to ensure
that samples are truly representative, and that the pesticide
residues to be measured are not degraded or the sample further
contaminated during handling and storage. Many methods of
detection are available, and the one chosen depends on the
physical and chemical properties of the pesticide as well as on
the equipment available.
A detailed review of all aspects of such analytical
procedures is beyond the scope of this document. However, a
brief summary of some of the procedures is given below.
A variety of techniques has been used for the determination
of thiocarbamate herbicide residues. Hughes & Freed (1961) used
gas-liquid chromatography (GLC) for the measurement of minute
amounts of EPTC in crops. This method is also being used for
the determination of other thiocarbamates. Another method in
use is a colorimetric procedure based on the determination of
the amine after hydrolysis of the thiocarbamate with
concentrated sulfuric acid (Batchelder & Patchett, 1960).
Other methods are available for the determination of EPTC: a
specific method based on gas chromatography (GC) and a method
based on Kjeldahl nitrogen determination. The recommended
method is GC when EPTC is determined with reference to a sample
of known composition (Patchett et al., 1964). EPTC residues
have also been determined by radiotracer techniques (Fang &
Theisen, 1959), by GC (Hughes & Freed, 1961), and by colorimetry
(Batchelder & Patchett, 1960). The GC method has mainly been
used in the analysis of soil samples, but the method can also be
used in the analysis of some crops. For routine crop sample
analyses, the colorimetric method is preferred, because of its
proved reliability and the low background values for a wide
range of sample types. If the equipment is available, a GC
method involving a microcoulometric detector for sulfur can be
used.
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE
3.1 Natural Occurrence
Cartap is a commercial insecticide developed from a zoogenic
substance, nereistoxin, which was found by Nitta in the body of
the marine segmented worm Lumbrineris (Lumbriconereis)
heterepoda, and isolated in 1934 (Okaichi & Hashimoto, 1962;
Sakai, 1969). The chemical structure of these two compounds are
as follows:
CH2-S-CO-NH2 CH2-S
/ /
(CH3)2N-CH (CH3)2N-CH |
\ \
CH2-S-CO-NH2 CH2-S
cartap nereistoxin
3.2 Man-Made Sources
Thiocarbamates are widely used throughout the world and are
produced in great quantities, mainly as herbicides and
fungicides.
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION
Like all pesticides, thiocarbamates can reach the soil via
many routes, ranging from direct application to drift from
foliage treatment. Generally, these compounds are not
persistent and undergo various types of degradation.
4.1 Transport and Distribution Between Media
4.1.1 Soil
4.1.1.1 Persistence and volatilization
Several factors are known to determine the persistence of
herbicides in soil. These include uptake and degradation by
soil microorganisms, pH, temperature, loss through physical
processes (volatilization, leaching), and chemical changes
(photodecomposition, chemical reaction). Volatilization is an
important mechanism in the loss of thiocarbamate herbicides from
soil (Anderson & Domsch, 1980). The loss of EPTC is greater
from moist soils than from dry. Loss through evaporation
correlates significantly with the amount of organic matter
present in the soil, the clay content, and leaching.
Consequently, these factors affect the herbicidal activity (Gray
& Weierich, 1968; Fang, 1975).
The persistence of thiocarbamates in soil, expressed as the
approximate half-life in moist soil, is given in Table 2 (Gray,
1971).
Fang (1975) reported that, during the first 15 min following
spraying on the soil surface, 20% of the applied EPTC
disappeared from dry soil, 27% from moist soil, and 44% from wet
soil. The losses were 23%, 49%, and 69%, respectively, after 1
day and 44%, 68%, and 90%, respectively, after 6 days.
Incorporation to a depth of 5 - 7.5 cm prevented severe loss of
EPTC from soil.
Cycloate was the least volatile of 5 herbicides tested,
followed by molinate, pebulate, vernolate, and EPTC in order of
increasing volatility. Increasing the temperature from 1.7 °C
to 37.7 °C caused an increase in the loss of vernolate from
moist and wet soils. The effect was more pronounced as the soil
moisture content increased (Fang, 1975).
Table 2. Persistence of thiocarbamate herbicides in moist soil
under simulated summer growing conditions
----------------------------------------------------------------
Herbicide Half-life in moist Half-life in Regina heavy
loam soil (21 - clay (25 °C) (weeks)a
32 °C) (weeks)a
________________________________________________________________
EPTC 1 4 - 5
Vernolate 1 - 2 2 - 3
Pebulate 2 2 - 3
Butylate 3 -
Molinate 3 -
Cycloate 3 - 4 -
Diallate > 4 5 - 6
Triallate - 10 - 12
----------------------------------------------------------------
a From: Stauffer Chemicals SA (1978).
4.1.1.2 Leaching
Quantitative leaching tests conducted in soils contained in
glass columns showed that thiocarbamate herbicides leach
downwards in direct relation to their water solubilities.
Molinate leached to the greatest depth followed by EPTC,
vernolate, pebulate, cycloate, and butylate in decreasing
order. Molinate and EPTC leached downwards to a depth of 22.5 -
37.5 cm in sandy soil when incorporated in the upper 7.5 cm of
soil at 11.2 kg/ha and leached with 20 cm of water, but the
other compounds stayed near the top 7.5 - 15 cm of soil when
leached with 20 cm of water. Leaching depth also decreased as
the organic matter content of the soil increased. In peat soil
(containing 35% organic matter), none of the thiocarbamate
herbicides leached out of the treated zone. The leaching data
indicated that, in most soils, the thiocarbamates stayed in the
upper 7.5 - 15 cm of soil. Under most conditions, the compounds
would disappear through microbial action before they could reach
the deeper layers of soil by leaching (Gray & Weierich, 1968;
Gray, 1971).
4.1.1.3 Lateral movement
The lateral movement of thiocarbamates was studied by
placing the compounds on filter paper discs, placed in the soil
together with weed seeds. Using ryegrass or oats as test
species, EPTC, vernolate, and pebulate moved laterally to form a
circle of weed control about 10 - 12.5 cm in diameter.
Molinate, cycloate, and butylate gave smaller zones of weed
control. The thiocarbamates also moved laterally more than most
other commercial herbicides as shown by their effect on grass
weeds. However, the size of the zone depended on both the
activity of the herbicide and the species tested. When a disc
containing EPTC was placed 7.5 cm deep in the soil, no zone of
weed control was detected. The data indicated that the
thiocarbamates moved outwards spherically when applied to a
concentrated spot in the soil. Because of this property of
lateral diffusion, thiocarbamates, applied by injection, have an
effective herbicide action (Gray, 1971).
4.2 Biotransformation
4.2.1 Microbial degradation
Soil microorganisms contribute significantly to the
disappearance of thiocarbamate herbicides from the soil
(Kaufman, 1967). However, the mechanism involved has not been
established, though it has been postulated that these compounds
could undergo hydrolysis at the ester linkage, with the
formation of a mercaptan and a secondary amine. The mercaptan
could then be converted into an alcohol by transthiolation, and
further oxidized to an acid, prior to entering the metabolic
pool. This mechanism has been proposed for the degradation of
EPTC and pebulate in plants and animals (Fang et al., 1964;
Kaufman, 1967) (Fig. 1).
Such a mechanism, i.e., hydrolysis followed by
transthiolation, could explain results observed in persistence
and degradation studies on diallate, carried out by Kaufman
(1967). In two separate studies, a bioassay analysis of treated
soil indicated a partial loss of phytotoxicity, followed by a
temporary increase in, and a subsequent complete loss of,
phytotoxicity. Hydrolysis of the diallate ester linkage,
followed by transthiolation of the allylic group, would result
in the formation of 2,3-dichloroallyl alcohol. However, the
results of unpublished studies indicate a more complex pathway
involving oxidative dealkylation of the amine (Stauffer
Chemicals SA, 1981).
Persistence tests in distilled water and tap water in clear
glass containers showed very slow degradation of thiocarbamates
by hydrolysis over a period of months. However, in pans of
water containing soil, microbes, and growing plants, molinate
and several other thiocarbamates disappeared rapidly within
several weeks (Gray, 1971).
4.2.2 Photodegradation
Little has been reported on the photodegradation of
thiocarbamates. Casida et al. (1975) exposed EPTC, butylate,
cycloate, molinate, vernolate, and pebulate to sunlight on thin-
layer-chromatographic (TLC) plates. After 16 h, none of the
original compounds could be recovered, but trace amounts of the
corresponding sulfoxides of EPTC and pebulate were found.
Minimum effects are to be expected on compounds in the solid
state, because of poor light penetration (DeMarco & Hayes,
1979).
DeMarco & Hayes (1979) studied the photodegradation of EPTC,
pebulate, and cycloate. The products identified for each
herbicide were the corresponding formamide, dialkylamine,
mercaptan, and disulfide, indicating a similar mode of
degradation. Fig. 2 shows a possible photodegradation pathway
suggested by DeMarco & Hayes (1979).
Absorption of light causes the breakage of the carbonyl C-S
bond producing two radicals. These can combine with protons from
the solvent giving the formamide and mercaptan. The formamide
is further degraded by ultraviolet radiation (UVR) to the
dialkylamine by the elimination of carbon monoxide. Collision
of two mercaptan radicals would lead to the formation of a
disulfide. Because the sulfur-sulfur bond is quite susceptible
to photolysis, continued exposure to UVR would result in a
return to separate mercaptan radicals, and the possible
reformation of the disulfide. Changes in the availability of
protons could influence the concentrations of mercaptan and
disulfide formed (DeMarco & Hayes, 1979).
5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE
Data on this subject were not available to the Task Group
with the exception of some occupational exposure data mentioned
in section 9.
6. KINETICS AND METABOLISM
6.1 Absorption, Distribution, and Excretion
Thiocarbamates in the form of an aerosol enter the organism
mainly via the respiratory tract. Absorption through the skin
and mucous membranes also occurs during occupational exposure,
and through the digestive tract.
In metabolic studies on rats, administered 14C-labelled
pebulate orally at 0.16 - 1.95 mg/animal (average weight 235 g),
the radioactivity was rapidly eliminated. An average of 51% was
excreted in the first 24 h and 80% after 3 days. Approximately
55% of the radioactivity was found in expired air as carbon
dioxide (CO2), while 23% was found in the urine and only 5% in
the faeces. Small amounts were detected in organs and tissues,
the highest levels being found in the liver, lungs, and kidneys
(Fang et al., 1964).
In a comparable study on rats, using labelled EPTC (dose
levels of 0.6 - 103 mg/animal), increasing the dose led to a
relative decrease in 14CO2 output with a corresponding increase
in the urinary excretion of radioactivity. Generally, 14CO2
elimination was complete within 15 h at lower dose levels, but
took approximately 35 h at higher doses (Ong & Fang, 1970).
Approximately 97% of an oral dose administered to rats at
72 mg molinate/kg body weight was excreted within 48 h. The
major routes of elimination were the urine (88%) and faeces
(11%); less than 1% was excreted as carbon dioxide (CO2). No
differences were found between males and females. With the
exception of blood, tissue residues decreased over a 7-day
period from an average of 13.8% to 3.7% (DeBaun et al., 1978a).
6.2 Metabolic Transformation
6.2.1 Mammals
One of the two major metabolic pathways for thiocarbamates
in mammals is sulfoxidation, followed by conjugation with
glutathione (GSH) by GSH S -transferase. The GSH conjugate is
then cleaved to the cysteine derivative, which is subsequently
acetylated and excreted as S -carbamoyl-mercapturic acid
(Hubbell & Casida, 1977; Chen & Casida, 1978). This metabolic
pathway is shown in Fig. 3.
Sulfoxidation of thiocarbamates such as EPTC, molinate,
pebulate, and vernolate undoubtedly represents a detoxification
mechanism in mammals, the sulfoxides generally being less toxic
than the parent compounds. The lower toxicity of the sulfoxides
is probably attributable to the high rate of cleavage and
elimination as glutathione conjugates (Casida et al., 1975).
The other mechanism is oxidation of the thiocarbamate
molecule. Metabolism of EPTC by a mouse liver microsome NADPH
system involves oxidative attack at the following sites in
decreasing order of importance: sulfur, alpha-carbon of the ethyl
group, alpha-carbon of the propyl group, ß-carbon of the propyl
group, y-carbon of the propyl group, and ß-carbon of the ethyl
group.
The metabolites hydroxylated at the carbons alpha to the
nitrogen and sulfur decompose at physiological pH, yielding S -
ethyl N -propylthiocarbamate in the case of the former, and
carbonylsulfide and acetaldehyde from the latter, compound. The
sulfoxide is further oxidized to the sulfone. The carbonyl-
sulfide undergoes further metabolism to carbon dioxide (CO2).
These findings indicate the major involvement of the sulfoxide
intermediate and also suggest that hydroxylation is an important
mechanism for thiocarbamate cleavage (De Matteis & Seawright,
1973; Dalvi et al., 1974, 1975; Chen & Casida, 1978).
In mice, urea was identified as one of the many urinary
metabolites. Since urea, amino acids, and small amounts of
propanethiol and propanol were found in the urine, the
thiolcarbamate molecule is probably hydrolysed at the ester
linkage to form n-propyl mercaptan, which is then converted to
propanol by a transthiolation (Fig. 1). The propanol may be
oxidized to a C-3 acid and/or further broken down to a C-2 unit
before entering the metabolic pool. Incorporation into tissue
constituents, such as protein and amino acids, may occur (Fang
et al., 1964; Ong & Fang, 1970).
The available metabolic pathways in rats differ for
thiocarbamates with n-alkyl substituents as opposed to those
with branched alkyl or cyclic substituents on the nitrogen.
Thus, the yield of mercapturic acids and the number of
metabolites are greater with the former than with the latter
(Hubbell & Casida, 1977). Sulfoxides can be detected as
transient metabolites in the liver of mice injected with EPTC,
molinate, or pebulate, but not with butylate or cycloate (Casida
et al., 1975). However, as cycloate and butylate are also
oxidized to sulfoxide, the appropriate mercapturic acid
derivatives can be detected in the urine (Hubbell & Casida,
1977).
Metabolic studies of [ring-14C] molinate in the rat were
carried out by DeBaun et al. (1978b). Unchanged molinate
accounts for only 0.1% of the urinary 14C after an oral dose of
72 mg labelled molinate/kg body weight. The major metabolic
pathway involves sulfoxidation and conjugation with glutathione,
giving rise to a mercapturic acid derivative that accounted for
35% of the urinary 14C. Ring hydroxylation to give 3- and 4-
hydroxymolinate conjugated as O-glucuronides represented
approximately 26%. Hydroxylation in the 2 position of the ring,
and subsequent ring cleavage, occurred only to a minor extent.
Hexamethyleneimine (14.6%) and 3- and 4-hydroxyhexamethylene-
imine (10.3%) were the major metabolites, presumably formed by
hydrolysis of sulfoxidized molinate and its hydroxy deriva-
tives.
6.2.2 Plants
The results of investigations with carbonyl 14C-labelled
materials showed that thiocarbamate herbicides are initially
metabolized in plants by the typical oxidation reactions
observed for other carbamate esters (Hubbell & Casida, 1977;
Carringer et al., 1978; Chen & Casida, 1978), i.e., thiol sulfur
oxidation to the corresponding sulfoxide. The sulfoxide is a
reactive intermediate and is capable of reacting with sulfhydryl
groups (e.g., in glutathione (GSH) or cysteine), to give the
carbamylated derivative (Horvath & Pulay, 1980). These two
conjugates were among the principal metabolites isolated from
the plants. The metabolism of thiocarbamate herbicides in
plants to the respective sulfoxides is of considerable
theoretical importance, since the sulfoxides are believed to be
responsible for the herbicidal activity of the thiocarbamates
(Casida et al., 1974). Furthermore, the reaction between GSH
and the thiocarbamate sulfoxide appears to result in
detoxification in plants. Antidotes such as N,N -diallyl-2,2-
dichloroacetamide, which protect plants from injury by
thiocarbamate herbicides, also increase the levels of GSH and
GSH S -transferase in the plant (Lay & Casida, 1976).
Current knowledge of the metabolism of thiocarbamates and
their mode of action is rather limited. It can be summarized as
follows. Thiocarbamates are readily absorbed by plants, but do
not remain as residues very long. It is generally believed
that, upon hydrolysis, thiocarbamates yield mercaptan, carbon
dioxide (CO2), and dialkylamine: a further cleavage of the
sulfur atom from the mercaptan is possible. Thus, the sulfur
atom can be subsequently incorporated into sulfur-containing
amino acids. The other part of the molecule will become carbon
dioxide (CO2) or will be incorporated into natural plant
constituents.
7. EFFECTS ON ORGANISMS IN THE ENVIRONMENT
7.1 Microorganisms
Endo et al. (1982) studied the influence of cartap on the
enzyme activities, respiration, and nitrification of the soil.
Soil was treated with cartap-HCl to give a final concentration
of 10, 100, or 1000 mg/kg (dry soil weight). The findings
suggested that nitrifying organisms were affected by 100 and
1000 mg cartap, but with 10 mg, no effects on enzyme activities,
respiration, or nitrification were found in soil kept under
upland or flooded conditions.
7.2 Aquatic Organisms
Data concerning the toxicity of thiocarbamates for aquatic
organisms are rather scarce. Acute toxicity data for fish are
given in Table 3, while those for a number of aquatic
invertebrates are summarized in Table 4.
7.3 Terrestrial Organisms
7.3.1 Birds
The results of a number of toxicity studies on birds,
lasting from 5 days to 2 months, are summarized in Table 5. The
results are expressed as LD50 in the diet or as no-observed-
adverse-effect levels. In the species tested, the toxicity of
thiocarbamates was low.
7.3.2 Honey bees
The toxicity (expressed as the LD50) of EPTC, molinate,
cycloate, butylate, pebulate, and vernolate for the honey bee
is > 11 µg/bee. From these results, it can be concluded that
these compounds are relatively non-toxic for the honey bee
(Stauffer Chemicals SA, 1978).
Table 3. Acute toxicity of thiocarbamates for fish
Organism Compound Weight of Temperature 96-h LC50 Comments
fish (g) (°C) (mg/litre)
Rainbow trout vernolate - - 9.6
( Salmo gairdneri)
Bluegill ( Lepomis vernolate - - 8.4
macrochirus)
Mosquitofish vernolate - - 14.5 Vernam 6Ea
( Gambusia affinis)
Rainbow trout vernolate 1.3 12 4.3b
( Salmo gairdneri) (3.9 - 4.7)
Table 3. (contd.)
Organism Compound Weight of Temperature 96-h LC50 Comments
fish (g) (°C) (mg/litre)
Bluegill ( Lepomis vernolate 1.2 24 2.5b
macrochirus) (1.7 - 3.7)
Rainbow trout EPTC - - 19
( Salmo gairdneri)
Bluegill ( Lepomis EPTC - - 27
macrochirus)
Cutthroat trout EPTC 1.0 10 17b
(15 - 19)
Lake trout EPTC 0.9 10 16.2b
(14.8 - 17. 7)
Rainbow trout molinate - - 1.3
( Salmo gairdneri)
Bluegill ( Lepomis molinate - - 29
macrochirus)
Channel catfish molinate - - > 3 no mortalityc
( Ictalurus punc-
tatus)
Carp ( Cyprinus molinate - - > 2 no mortalityd
carpio)
Bluegill ( Lepomis molinate - - > 1 no mortalitye
macrochirus)
Rainbow trout cycloate - - 4.5
( Salmo gairdneri)
Bluegill ( Lepomis cycloate - - 5.6
macrochirus)
Mosquitofish cycloate - - 10 Ro-Neet 6Ef
( Gambusia affinis)
Rainbow trout butylate - - 4.2
( Salmo gairdneri)
Bluegill ( Lepomis butylate - - 6.9
macrochirus)
Mosquitofish butylate - - 8.5 Sutan 6Eg
( Gambusia affinis)
Table 3 (contd).
Organism Compound Weight of Temperature 96-h LC50 Comments
fish (g) (°C) (mg/litre)
Rainbow trout pebulate - - 7.4
( Salmo gairdneri)
Bluegill ( Lepomis pebulate - - 7.4
macrochirus)
Mosquitofish pebulate - - 10 Tillam 6Eh
( Gambusia affinis)
Rainbow trout diallate - - 7.9
( Salmo gairdneri)
Bluegill ( Lepomis diallate - - 5.9
macrochirus)
Rainbow trout triallate - - 1.2
( Salmo gairdneri)
Bluegill ( Lepomis triallate - - 1.3
macrochirus)
a Vernam 6E: herbicide formulation (vernolate).
b From: Johnson & Finley (1980). Other data from: Stauffer Chemicals SA (1978)
and Worthing & Walker (1983).
c After 11 days.
d After 21 days.
e After 35 days.
f Ro-Neet 6E: herbicide formulation (cycloate).
g Sutan 6E: herbicide formulation (butylate).
h Tillam 6E: herbicide formulation (pebulate).
Table 4. Acute toxicity of thiocarbamates for aquatic invertebratesa
-----------------------------------------------------------------------
Organism Compound Stage Temperature 96-h LC50
(°C) (mg/litre)
Asellus communis EPTC mature 15 23b
(isopod) (15 - 36)
Gammarus fasciatus EPTC mature 15 66b
(shrimp)
Cypridopsis vernolate mature 21 0.25b,c
(0.15 - 0.42)
Asellus communis vernolate mature 15 0.23c
(isopod) (0.16 - 0.33)
Gammarus fasciatus vernolate mature 15 14
(shrimp) (9.6 - 20)
Palaemonetes sp. vernolate juvenile 2.1 0.53c
(shrimp) (0.14 - 2.0)
a From: Johnson & Finley (1980).
b 48-h EC50.
c Tested in hard water (272 mg CaCO3/litre).
Table 5. Toxicity of thiocarbamates for birdsa
Product Species Protocol Dose (mg/kg diet) Results
(mg/kg diet)
-------- --------------- ---------------------------- ----------------- ---------------------------
EPTC bobwhite quail 7-day dietary administration 1000 - 32 000 LD50 in diet: 20 000;
of technical EPTC no-observed-adverse-effect
level > 1800
Molinate mallard duck 5-day dietary administration 1000 - 32 000 LD50 in diet: 13 000
Cycloate bobwhite quail 7-day dietary administration 1800 - 56 000 LD50 in diet: 56 000
of Ro-Neet 6Eb
Butylate bobwhite quail 7-day dietary administration 1800 - 56 000 LD50 > 56 000
Pebulate bobwhite quail 7-day dietary administration 1000 - 18 000 LD50 in diet: 8400
of technical pebulate
Pebulate bobwhite quail 7-day dietary administration 1000 - 24 000 LD50 in diet; 9500
of Tillam 6Eb
Vernolate bobwhite quail 7-day dietary administration 1800 - 24 000 LD50 in diet: 12 000
of technical vernolate
a From: Stauffer Chemicals SA (1978).
b Herbicide formulation.
8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS
Yin-Tak Woo (1983) has reviewed the structure-activity
relationships for the different types of thiocarbamates.
8.1 Single Exposures
Data concerning the acute toxicity of thiocarbamates are
summarized in Table 6. Very few results on acute inhalatory
toxicity are available.
The acute oral and dermal toxicities of thiocarbamates are
relatively low. The most toxic representatives of the
thiocarbamates are molinate and diallate. The toxicity of EPTC
for various animal species varies significantly. The cat seems
to be the most sensitive animal species. It should be noted
that this may also be true for other thiocarbamates, but data on
the cat are lacking.
When animals are administered high oral dose levels of
thiocarbamates, signs such as anorexia, squinting, hyper-
salivation, lachrymation, piloerection, laboured breathing,
ataxia, hypothermia, incoordination, depression, pareses, and
muscular fibrillation may be observed, and convulsions followed
by death may occur (Akulov et al., 1972; IARC, 1976).
Lethal doses of diallate given to rats and guinea-pigs
caused restlessness within the first 2 h, followed by lack of
coordination. Animals died from respiratory paralysis. Autopsy
revealed vascular dilatation in the cerebrum, cerebellum, and
abdominal viscera, meningeal haemorrhages, and enlarged adrenal
glands (Doloshitsky, 1969).
In rabbits, a single oral dose of triallate (450 - 500 mg/kg
body weight) decreased acetylcholinesterase (AChE) activity in
some parts of the brain and in red blood cells. The maximum
levels of inhibition were less than 20% in the brain and 42% in
the red blood cells (Zhavoronkov et al., 1974).
8.2 Short- and Long-Term Exposure
8.2.1 Experimental animals
Doloshitsky (1969) carried out studies on albino rats
receiving dose levels of 0.5 - 200 mg diallate/kg body weight
for periods of up to 8 months. Dose levels of 20 mg/kg or more
resulted in a clear increase in mortality. At 50 mg/kg body
weight, 73% of the animals died within 8 months.
Table 6. Acute toxicity of thiocarbamates for experimental animals
Compound Animal Dose Reference
(mg/kg body weight)
Oral Dermal
Butylate rat (male) 3500 - Worthing & Walker
(1983)
rat (female) 3970 - Worthing & Walker
(1983)
rabbit > 2000 Hubbell & Casida
(1977)
Diallate rat 395 Worthing & Walker
(1983)
rat 1000 Doloshitsky
(1969)
rabbit 2000 - 2500 Worthing & Walker
(1983)
dog 510 Worthing & Walker
(1983)
Triallate rat 1471 Rappoport & Pest-
ova (1973)
rat 1675 - 2165 Worthing & Walker
(1983)
rabbit 8200 Worthing & Walker
(1983)
Pebulate rat 1120 Worthing & Walker
(1983)
rabbit 4640 Worthing & Walker
(1983)
Vernolate rat 1780 Stauffer Chemicals
SA (1978)
Molinate rat (male) 369 Worthing & Walker
(1983)
rat (female) 450 Worthing & Walker
(1983)
rabbit > 4640 Worthing & Walker
(1983)
Cycloate mouse 2285 Rebrin & Alexan-
drova (1971)
rat 2710 Worthing & Walker
(1983)
rabbit > 4640 Worthing & Walker
(1983)
EPTC rat 1630 3200 Hubbell & Casida
(1977)
Worthing & Walker (1983) summarized short-term toxicity
tests of a number of thiocarbamates. Rats were administered
400 mg diallate/kg diet for 90 days. Weight loss, irritability,
hyperactivity, and mild cardiac changes, but no deaths, occurred
at 1200 mg/kg diet, the highest dose level tested. In beagle
dogs, adverse effects were observed at 600 mg/kg body weight per
day, but not at 125 mg/kg body weight per day. In a 2-year
feeding trial, no adverse effects were observed in rats
receiving 200 mg triallate/kg diet or in dogs receiving
15 mg/kg, daily. Cycloate did not induce toxicity symptoms in
dogs administered 240 mg/kg daily for 90 days, and butylate was
well tolerated by rats and dogs at a dose level of 40 mg/kg
daily for 90 days.
Rats fed 147 mg triallate/kg body weight in the diet (one-
tenth of the LD50), for 1, 2, or 3 months, showed congestion,
perivascular oedema, chromatolysis, and proliferation of
adventitial cells in the brain. Local fatty degeneration and
dystrophy in the liver and kidneys were also observed (Rappoport
& Pestova, 1973).
8.2.2 Domestic animals
Sheep administered daily oral doses of diallate at 10 mg/kg
body weight for 19 weeks, 25 mg/kg for 20 - 24 weeks, and
50 mg/kg for 25 and 26 weeks became ill only when the dose was
increased to 50 mg/kg body weight. Cholinesterase activity
remained normal. It seems that 10 mg diallate/kg body weight
did not cause any toxic effects (Palmer et al., 1972).
Single oral doses of 300 mg triallate/kg and 720 mg
triallate/kg body weight to sheep and pigs, respectively,
decreased RNA and DNA levels in the leukocytes and increased the
concentration of free nucleotides (Verkhovskiy et al., 1973).
8.3 Skin and Eye Irritation; Sensitization
Worthing & Walker (1983) summarized the skin and eye
irritation potential of a number of thiocarbamates. Butylate is
a mild irritant to the skin and non-irritating to eyes; cycloate
is non-irritating to eyes; diallate is a moderate irritant to
the skin and eyes; molinate is non-irritating to skin and
moderately irritating to eyes; and triallate is moderately
irritating to skin and slightly to eyes. These compounds were
all tested on the skin and eyes of rabbits.
8.4 Reproduction, Embryotoxicity, and Teratogenicity
8.4.1 Reproduction
Daily administration of 3.6 mg molinate/kg body weight for 2
months to 7- to 8-week-old rats caused gonadal and spermatozoal
changes. When intact females were mated with treated males,
resorption, impaired fetal development, and increased lethal
effects in offspring were seen. Unlike molinate, pebulate
administered to male rats at 11.25 mg/kg body weight, daily, for
2 months, did not induce any gonadotoxic effects (Voytenko &
Medved, 1973).
8.4.2 Teratogenicity
Pregnant CF1 mice, Sprague Dawley rats, and golden hamsters
were given cartap hydrochloride orally on days 8 - 13 (mice,
hamsters) or days 9 - 15 (rats) of gestation at dose levels of
50 - 100 mg/kg body weight for mice and rats and 2 - 100 mg/kg
body weight for hamsters. Mice receiving 50 mg and 100 mg, rats
receiving 50 mg, and hamsters receiving 2, 10, and 50 mg/kg
tolerated administration of cartap, except that maternal death
occurred in rats at 50 mg/kg body weight. No significant
increases in fetal abnormalities were found. Treatment of rats
and hamsters with 100 mg/kg body weight resulted in maternal
death and retarded growth. However, the rates of embryonal
resorption and gross malformations were comparable with those in
the controls. Cartap did not induce any fetotoxic or
teratogenic effects in this study (Mizutani et al., 1971).
8.5 Mutagenicity and Related End-Points
Diallate and triallate were mutagenic in the Ames test,
with Salmonella typhimurium strains TA 100 and TA 1535 (base-
pair substitution mutants), but only in the presence of liver
microsomal preparation, indicating the need for chemical
activation. No effects were seen with strains TA 98 and TA 1538
(frameshift mutants) (Sikka & Florczyk, 1978). The mutagenic
activity of these compounds seems to be related to the presence
of the chloroallyl group in the molecule, which is, in fact,
very similar to the known carcinogen and mutagen vinyl
chloride.
Cartap was tested in vivo for cytogenic effects on the bone
marrow cells of CF1 mice and Wistar rats. The compound was
administered at levels of 10, 100, or 150 mg/kg body weight to
adult male rats, in either a single dose or daily for 5
successive days. Cartap was also administered to 3-week-old rats
at an oral dose of 200 mg/kg body weight or intraperitoneally
(ip) at a dose of 30 mg/kg body weight. No chromosomal aber-
rations were found. No mutagenic effects were seen in male mice
using the dominant lethal test after a single, or 5 successive,
oral doses of 100 mg/kg body weight (Kikuchi et al., 1976).
Murnik (1976) showed that butylate and vernolate
significantly increased the level of apparent dominant lethals
in Drosophila melanogaster, probably because of toxicity, since
genetic assays did not clearly indicate an induction of
chromosomal breakage or loss. An increased frequency of sex-
linked recessive lethals was found.
8.6 Carcinogenicity
Increased tumour incidence was observed in mice given
diallate orally at 125 mg/kg body weight per day, from the 7th
day of life, for 4 weeks, and 560 mg/kg diet for a further 73
weeks (Innes et al., 1969).
9. EFFECTS ON MAN
9.1 Occupational Exposure
Data concerning the effects of thiocarbamates on man are
scarce. When soil was treated with Eptam by aircraft and
tractor, the air levels of the herbicide in the working zone
ranged from 8.1 to 210 mg/m3. Some workers reported headache
and nausea, especially following exposure to 135 -210 mg EPTC/m3
(Medved & Ivanova, 1971) and also following brief exposure to
diallate. Skin irritation was also found.
10. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES
The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) and
the International Agency for Research on Cancer (IARC) have
evaluated the toxicity and carcinogenicity data of a few
thiocarbamates. These are referred to in Annex II.
This Annex also gives the WHO recommended hazard
classification. As indicated, WHO/FAO Data Sheets, IRPTC Data
Profiles, and IRPTC Legal Files are not available for these
thiocarbamates.
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Annex I. Names and structures of selected thiocarbamates
Common Trade/ Chemical structure CAS chemical name/ Molecular Relative Vapour Water
name other CAS registry number formula molec- pres- solu-
name ular sure bility
mass (25 °C) (25 °C)
butylate Sutan [(CH3)2CHCH2]2NCOSCH2CH3 carbamothioic acid, C11H23NOS 217.41 170 mPa 46
bis(2-methyl-propyl)-, mg/
S -ethyl ester litrea,b
(2008-41-5)
cartap Padan O carbamothioic acid, C7H15N3O2S 205
|| S,S'-[2-(dimethyl-
(H2N-C-SCH2)2-CH-N(CH3)2 amino)-1,3 propane-
diyll ester
(15263-53-3)
cycloate Ro-Neet O carbamothioic acid, C11H21NOS 215.39 830 mPa 75
Eurex ___ || ethyl(cyclo-hexyl)-, mg/
/ \-N-C-SC2H5 S -ethyl ester litrea,b
\ / | (1134-23-2)
C2H5
diallate Avadex carbamothioic acid, C10H17Cl2NOS 270.24 20 mPa 14
DATC O bis(1-methyl-ethyl)-, mg/
|| S -(2,3-dichloro-2- litreb
[(CH3)2CH]2N-C-SCH2-C-CHC1 propenyl) ester
| (2303-16-4
Cl
EPTC Eptam carbamothioic acid, C9H19NOS 189.35 4.5 Pa 370
Eradicane O bis(1-methyl-ethyl)-, mg/
R-1608 || S -ethyl ester litrea
[(CH3)2CH]2N-C-SC2H5 (759-94-4)
ethiolate Prefox O carbamothioic acid, C7H15NOS 161.29
|| diethyl-, S -ethyl
(C2H5)N-C-SC2H5 ester
(2941-55-1)
Annex I (contd).
Common Trade/ Chemical structure CAS chemical name/ Molecular Relative Vapour Water
name other CAS registry number formula molec- pres- solu-
name ular sure bility
mass (25 °C) (25 °C)
molinate Ordram CH2CH2CH2 O 1H-azepine-1-carbo C9H17NOS 187.33 746 mPa 880
Yalan | \ || thioic acid, hexa- mg/
| N-C-SC2H5 hydro-, S -ethyl litrea,b
| / ester
CH2CH2CH2 (2212-67-1)
pebulate Tillam O carbamothioic acid, C10H21NOS 203.38 4.7 Pa 60
PEBC || butylethyl-, mg/
C2H5-N-C-SC3H7 S -propyl ester litrea,b
| (1114-71-2)
C4H9
prothio- Dynone carbamothioic acid, C8H18N2OS 226.8 1.9 uPa
carb O [3-(dimethyl-amino)-
|| propyl]-, S -ethyl
(CH3)2N-C3H7NH-C-SC2H5 ester
(19622-19-6)
triallate Avadex BW O carbamothioic acid, C10H14Cl3NOS 304.68 16 mPa 4
Far-Go || bis(1-methyl-ethyl)-, mg/
[(CH3)2CH]2N-C-S-CH2C-CCl2 S -(2,3,3-trichloro- litreb
| 2-propenyl) ester
Cl (2303-17-5)
vernolate R-1607 O carbamothioic acid, C10H21NOS 203.38 1.39 Pa 107
Vernam || dipropyl-, S -propyl mg/
(C3H7)2N-C-SC3H7 ester litre
(1929-77-7)
a At 20 °C.
b From: Worthing & Walker (1983).
Annex II, Table 1. Thiocarbamates: JMPR reviews, ADIs, Evaluation by IARC,
Classification by Hazard, FAO/WHO Data Sheets, IRPTC Data profile and
Legal filea
Compound Year of ADIb Evaluation by IARCd Availability WHO recom- FAO/WHO Data
JMPR (mg/kg JMPRc: Evaluation of IRPTCe: mended clas- sheets on
meeting body Published in: of carcino- Data Legal sification pesticidesf
weight) FAO/WHO genicity profile fileg of pesticides
by hazardh
Butylate 0
Cartap 1978 0-0.1 1979 II
1976 0-0.5 1977b
(temporary)
1977a
Cycloate III
Diallate 1976 II
EPTC II
Molinate II
Pebulate II
Prothiocarb III
Triallate III
Vernolate II
a Adapted from: Vettorazzi & Van den Hurk (1984).
b ADI = acceptable daily intake.
c JMPR = Joint Meeting on Pesticide Residues (FAO/WHO).
d IARC = International Agency for Research on Cancer, Lyons, France.
e IRPTC = International Register for Potentially Toxic Chemicals (UNEP, Geneva).
f WHO/FAO Data Sheets on Pesticides with number and year of appearance.
g From: IRPTC (1983).
h From: WHO (1986).
The hazard referred to in this classification is the acute risk for health (that is, the
risk of single or multiple exposures over a relatively short period of time) that might be
encountered accidentally by a person handling the product in accordance with the directions
for handling by the manufacturer, or in accordance with the rules laid down for storage and
transportation by competent international bodies.
The classification relates to the technical material and not to the formulated product.
Annex II, Table 2. WHO recommended hazard classification for
pesticides
Class LD50 for the rat (mg/kg body weight)
Oral Dermal
-------------------- ----------------------
Solids Liquids Solids Liquids
1a Extremely hazardous 5 or less 20 or less 10 or less 40 or less
1b Highly hazardous 5 - 50 20 - 200 10 - 100 40 - 400
II Moderately hazardous 50 - 500 200 - 2000 100 - 1000 400 - 4000
III Slightly hazardous over 500 over 2000 over 1000 over 4000
O Unlikely to present
acute hazard in normal
use