Dimethylarsinic acid, methanearsonic acid, and salts (HSG 69, 1992)

IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 69

DIMETHYLARSINIC ACID, METHANEARSONIC ACID, AND SALTS
HEALTH AND SAFETY GUIDE

UNITED NATIONS ENVIRONMENT PROGRAMME

INTERNATIONAL LABOUR ORGANISATION

WORLD HEALTH ORGANIZATION

WORLD HEALTH ORGANIZATION, GENEVA 1992

Published by the World Health Organization for the International
Programme on Chemical Safety (a collaborative programme of the
United Nations Environment Programme, the International Labour
Organisation, and the World Health Organization)

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

WHO Library Cataloguing in Publication Data

Dimethylarsinic acid, methanearsonic acid, and salts: health and
safety guide.

(Health and safety guide ; no. 69)

1. Arsenicals - standards 2. Arsenicals - toxicity
3. Environmental exposure I.Series

ISBN 92 4 151069 2 (NLM Classification: QV 294)
ISSN 0259-7268

The World Health Organization welcomes requests for permission to
reproduce or translate its publications, in part or in full.
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CONTENTS

INTRODUCTION

NOTE TO READERS

1. PRODUCT IDENTITY AND USES
1.1. Identity
1.2. Physical and chemical properties
1.3. Analytical methods
1.4. Production and uses

2. SUMMARY AND EVALUATION
2.1. Human exposure
2.2. Effects on organisms in the environment
2.3. Uptake, metabolism, and excretion
2.4. Effects on experimental animals
2.5. Effects on humans

3. CONCLUSIONS AND RECOMMENDATIONS
3.1. Conclusions
3.2. Recommendations

4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY
ACTION
4.1. Human health hazards, prevention and
protection, first aid
4.1.1. First aid
4.2. Advice to physicians
4.2.1. Treatment
4.3. Explosion and fire hazards
4.4. Storage and transport
4.5. Spillage
4.6. Disposal

5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
6.1. Previous evaluations by international bodies
6.2. Exposure limit values
6.3. Specific restrictions
6.4. Transport and labelling

BIBLIOGRAPHY

INTRODUCTION

This Health and Safety Guide is not based on an existing
Environmental Health Criteria document, but on critical national
reviews. The hazard evaluation in the Health and Safety Guide was
made on the basis of carefully selected studies, after scrutiny of
the original publications.

In order to assist the peer-review process of the present Health and
Safety Guide, a background companion document was prepared by the
IPCS and can be obtained from the Director on request; the IPCS does
not intend that the background document should be published.

The first three sections of this Health and Safety Guide present
essential technical information and the hazard evaluation. Section 4
includes advice on preventive and protective measures and emergency
action; health workers should be thoroughly familiar with the
medical information to ensure that they can act efficiently in an
emergency. The section on regulatory information has been extracted
from the legal file of the International Register of Potentially
Toxic Chemicals (IRPTC) and from other United Nations sources.

The target readership includes occupational health services, those
in ministries, governmental agencies, industry, and trade unions who
are involved in the safe use of chemicals and the avoidance of
environmental health hazards, and those wanting more information on
this topic. An attempt has been made to use only terms that will be
familiar to the intended user. However, sections 1 and 2 inevitably
contain some technical terms.

Revision of the information in this Guide will take place in due
course, and the eventual aim is to use standardized terminology.
Comments on any difficulties encountered in using the Guide would be
very helpful and should be addressed to:

The Director
International Programme on Chemical Safety
World Health Organization
1211 Geneva 27
Switzerland

THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING
POINT TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME

NOTE TO READERS

Organic arsenic compounds comprise a large number of alkyl and aryl
derivatives; these have widely different uses and toxicological
properties and do not form a homogeneous group. Also, the available
information on most of these compounds is insufficient to allow for
an adequate evaluation of the health and environmental hazards
associated with their use. For these reasons, this Health and Safety
Guide deals only with dimethylarsinic acid, methanearsonic acid, and
their sodium salts.

It is important to emphasize, however, that some of the compounds
not covered in this Guide are more hazardous than the derivatives
that are described, and should be handled with great caution.

1. PRODUCT IDENTITY AND USES

1.1 Identity

The formulas, chemical names, CAS numbers, synonyms and trade names
of the dimethylarsinic and methanearsonic acids and their sodium
salts are included in Table 1.

1.2 Physical and chemical properties

Dimethylarsinic acid is stable in storage. Nascent hydrogen, formed
by the action of acids on active metals, will reduce the substance
to highly toxic dimethylarsine. Aqueous solutions are mildly
corrosive. Some physical properties of these compounds are shown
above, in Table 2.

1.3 Analytical methods

The most common method involves reduction to the corresponding
arsine by sodium-borohydride, followed by determination of the
latter by atomic-absorption spectroscopy.

Another sensitive method for the separation and quantitative
determination of arsenical pesticide residues and their metabolites
is based on the use of high-pressure liquid chromatography coupled
with graphite furnace, atomic-absorption spectroscopy.

Paper chromatographic separation and detection methods, as well as
the use of ion-exchange chromatography in combination with
thin-layer chromatography, have been described for the determination
of dimethyl-arsinic acid and other organic arsenical compounds.

1.4 Production and uses

Substantial amounts of methanearsonic acid, dimethylarsinic acid
(cacodylic acid), and their salts, are used as non-selective contact
herbicides, especially for the control of Johnson grass in cotton
fields. Dimethylarsinic acid is used extensively in some areas for
cotton defoliation. It has also been used as an insecticide (e.g.,
against bark beetles), as a soil sterilant, and as a silvicide in
forest control (timber thinning).

Dimethylarsinic acid (cacodylic acid) is available as a technical
grade product, containing 65% active ingredient and the following
possible impurities: sodium chloride, sodium sulfate, methanearsonic
acid, and arsenic acid.

Table 1. Formulas, chemical names and synonyms of dimethylarsinic and methanearsonic acids
and their sodium salts

Chemical name Formula CAS-No. Synonyms and trade names

Dimethylarsinic (CH₃)₂AsO(OH) 75-60-5 Arsine oxide, hydroxydimethyl-;
acid arsinic acid, dimethyl-; cacodylic
acid; hydroxy-dimethylarsine oxide;
Agent Blue; Ansar 138; Arsan; Dilic;
Phytar 138; Phytar 560; Rad-E-Cate
25; Silvisar 510

Methanearsonic CH₃AsO(ONa)₂ 144-21-8 arsinyl; arsonic acid, methyl-,
acid, disodium disodium salt; disodium
salt methanearsenate; disodium
methanearsonate; disodium
methylarsonate; Arrhenal; Ansar 184;
Ansar 8100; Ansar DSMA Liquid;
Arsynal; Cacodyl New; Chipco Crab
Kleen; Cralo-E-Rad; Dal-E-Rad 100;
Diarsen; Disomear; Di-Tac; DMA;
DMA 100; DSMA; DSMA Liquid;
Methar; Metharsan; Metharsinat;
Namate; Neo-Asycodile; Sodar;
Somar; Stenosine; Tonarsen; Tonarsin;
Weed Broom; Weed-E-Rad;
Weed-E-Rad DMA Powder;
Weed-E-Rad 360; Weed-Hoe

Table 1 (continued)

Chemical name Formula CAS-No. Synonyms and trade names

Methanearsonic CH₃AsO(OH)ONa 2163-80-6 Arsonic acid, methyl-, monosodium
acid, mono- salt; monosodium acid
sodium salt methanearsonate; sodium
monosodium acid metharsonate;
monosodium methanearsonate;
monosodium methylarsonate; MSMA;
sodium acid methanearsonate;
methylarsenic acid, sodium salt;
Ansar 170H.C.; Ansar 170 L; Ansar
529 H.C.; Arsonate Liquid; Bueno 6;
Daconate 6; Dal-E.Rad; Herb-All;
Merge 823; Mesamate; Mesamate
H.C.; Mesamate Concentrate;
Mesamate 400; Mesamate 600;
Phyban H.C.; Silvisar 550; Target
MSMA; Trans-Vert; Weed 108;
Weed-E.Rad; Weed-Hoe

Sodium (CH₃)₂AsO(ONa) 124-65-2 Arsine oxide, hydroxydimethyl-,
cacodylate sodium salt; arsinic acid, dimethyl-
sodium salt; cacodylic acid, sodium
salt; [(dimethylarsino)oxy]-sodium-As-
oxide; hydroxydimethylarsine oxide,
sodium salt; sodium dimethylarsinate;
sodium dimethylarsonate; Alkarsodyl;
Arsecodile Arsicodile; Arsycodile;
Boll's Eye; Phytar 560; Rad-E-Cate 25;
Silvisar

Table 2: Physical properties of dimethylarsinic acid and its sodium salt and of methanearsonic
acid monosodium and disodium salts

Compound Melting point (°C) Description Solubility (g/litre)

Dimethylarsinic 195-196 white, very soluble in water (2000),
acid crystalline ethanol; insoluble in ether
solid

Methanearsonic 132-139 crystalline very soluble in water (1000),
acid disodium solid methanol; insoluble in organic
salt solvents

Methanearsonic 115-119 crystalline soluble in water (570), methanol;
acid mono- solid insoluble in organic solvents
sodium salt

Sodium 200 crystalline very soluble in water (2000);
cacodylate solid soluble in ethanol

Methanearsonic acid, disodium salt, is available for farm
applications as a solution containing added surfactant.
Methanearsonic acid, monosodium salt, is available for farm
applications as a technical grade product in combination with a
surfactant, or in combination with sodium cacodylate,
dimethylarsinic acid, and a surfactant.

Sodium cacodylate is available for farm applications as concentrated
solutions, as a 25% solution with surfactant, in combination with
dimethyl-arsinic acid or in combination with methane-arsonic acid,
monosodium salt, and surfactant.

2. SUMMARY AND EVALUATION

2.1 Human exposure

Since inorganic arsenic can be converted to methylated species by
living organisms, human exposure to these compounds through food is
universal. Arsenic in fish is mainly present as organic compounds,
which, in general, are less toxic than the inorganic derivatives.
Marine fish and crustaceans commonly contain 2-20 mg arsenic/kg on a
wet weight basis, although higher values (up to 50-100 mg/kg) have
been reported.

In occupational exposure, inhalation is the main route of
absorption.

2.2 Effects on organisms in the environment

The acute toxicities of dimethylarsinic acid and its salts for fish
are moderate to low. The long-term effect of methylated arsenicals
on non-target organisms is not known. Biological transformations in
soil result in the production of more toxic arsenic compounds, such
as the volatile dimethyl- and trimethylarsines, as well as inorganic
arsenic. In a model ecosystem, algae and daphnia accumulated these
compounds. Methyl arsenic derivatives are phytotoxic. Very few
studies are available on the environmental effects of organoarsenic
compounds.

2.3 Uptake, metabolism, and excretion

Following ingestion or inhalation, methylated arsenic compounds are
rapidly and extensively taken up by mammals, including humans. They
are eliminated, mainly in the urine, within a period of 2-4 days.
Apart from species-related retention in the red blood cells of rats,
no appreciable accumulation seems to occur in mammals.
Dimethylarsinic acid penetrates the intact skin, and has been shown
to cross the placental barrier. In the hamster, dimethylarsinic acid
forms small amounts of volatile arsines, such as trimethylarsine.

2.4 Effects on experimental animals

In contrast to most inorganic arsenic compounds, the acute oral,
dermal, and inhalation toxicities of methylated arsenic compounds
for mammals are low to very low. Ruminants appear to be more
susceptible, and several reports of intoxication of domestic animals
have been published; the clinical signs and histological findings
seem to have been similar to those induced by inorganic arsenic.
The long-term administration of methylated arsenic compounds to
rabbits and rats has induced signs of toxicity at relatively low
doses. However, the carcinogenicity of these compounds in animals
has not been sufficiently investigated.

Although the results from most tests for genotoxicity using
dimethylarsinic acid have been negative, some positive findings have
been reported. Embryotoxic as well as teratogenic effects of
dimethylarsinic acid have been reported in mice and hamsters. In
rats, a no-effect level for embryotoxicity of 15 mg/kg body weight
per day has been found in one oral study. No reproduction studies
have been found in the literature.

2.5 Effects on humans

No data are available on toxic effects in humans; the risk
evaluation is based on the demonstrated effects of these substances
on experimental animals. It is likely that if poisoning does occur
in humans, the effects will be similar to those produced by
inorganic arsenic compounds.

3. CONCLUSIONS AND RECOMMENDATIONS

3.1 Conclusions

Dimethylarsinic acid and methanearsonic acid salts are characterized
by a low acute toxicity in mammals, although ruminants appear to be
more susceptible. Although insufficiently investigated, there are
indications that the toxicity is higher with long-term exposure.
Information on the toxicological properties of methanearsonic acid
salts is fragmentary, but these substances seem to have
toxicological properties similar to those of the dimethyl
derivatives.

Dimethylarsinic acid is decomposed in the environment to either
inorganic arsenic, or highly toxic volatile arsines. Thus, extensive
use as a pesticide may result in undesired long-term effects by
increasing the total arsenic load in the ecosystem.

3.2 Recommendations

Methylated arsenic compounds and their salts should be replaced by
less hazardous substitutes, wherever this is feasible.

4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY
ACTION

4.1 Human health hazards, prevention and protection, first aid

In order to interrupt the chain of generation/release/transmission
of the hazardous agent, the main goal should be primary prevention
through interventions in the work environment. These include
measures such as exhaust ventilation, closed systems, enclosure of
sources, and good housekeeping practices. Local exhaust ventilation
systems must include air cleaning devices to prevent environmental
pollution.

When these measures are not technically feasible, as is the case in
the formulation or application of pesticides, or in the case of
temporary operations, the use of personal protective clothing and
equipment (e.g., disposable dust masks) is recommended.

The following precautions should be observed during handling and
use:

* Avoid contact with the skin and eyes by using a face-mask and
complete protective clothing.

* Do not smoke, drink, or eat in the workplace. Wash hands and
any exposed skin before eating, drinking, or smoking, and after
work.

Regular medical supervision of workers occupationally exposed to
organic arsenic compounds is recommended.

4.1.1 First aid

Medical attention should be obtained; in the meantime, first aid
should be provided immediately. If material has been spilled on the
skin, immediately remove the patient from the source of
contamination, remove all contaminated clothing, and wash the
affected areas with soap and water. If the material is in the eyes,
flush with clean water for 5-10 minutes. In the case of ingestion,
immediate action is imperative: if the patient is conscious, give
two glasses of milk or water, or a beaten egg, induce vomiting, and
subsequently administer activated charcoal, if possible. Transport
the patient to a hospital.

4.2 Advice to physicians

Diagnosis is based on history, symptoms, signs, and laboratory
confirmation of a raised arsenic level in the urine, but treatment
should start on suspicion of poisoning.

Although it is unlikely that in normal use these compounds will
induce acute poisoning, signs of acute poisoning are likely to be
similar to those of inorganic arsenic compounds and could include
nausea, vomiting, abdominal pain, and diarrhoea.

4.2.1 Treatment

Prognosis is dependent on dose, as well as the time between
ingestion of the arsenical compound and first treatment. Gastric
aspiration and lavage with warm water, followed by administration of
sodium sulfate (30 g) is indicated. Keep the patient warm and quiet;
combat shock and dehydration. Apply artificial respiration, oxygen
therapy, whole blood, or fluids as needed. It is unlikely that
chelation will be required, but if it is, dimercaprol (BAL), by
intramuscular injection, has been found to be useful in cases of
intoxication. A number of side-effects have been associated with
BAL, and the use of this antidote for the treatment of chronic
intoxications is controversial. D-penicillamine has also been used,
although its efficacy has been questioned. A water-soluble analogue
of dimercaprol (meso-2,3-dimercaptosuccinic acid - DMSA) has proved
to be more effective and less toxic; therefore, it is indicated as
first-choice chelator, if available. The sodium salt of
2,3-dimercaptopropanesulfonate (Unithiol, Dimaval, DMPS) has also
been reported to be effective, and to induce less severe
side-effects than dimercaprol.

4.3 Explosion and fire hazards

Organic arsenic compounds may give off highly toxic fumes when
heated. Dimethylarsinic acid may be decomposed by powerful oxidizing
or reducing agents. Most fire-extinguishing agents can be used to
combat fires involving arsenic. However, the use of water sprays
should be confined to the cooling of unaffected stock only, thus
avoiding the accumulation of polluted run-off from the site.
Fire service personnel should be advised that self-contained
breathing apparatus and totally encapsulated protective clothing is
necessary.

4.4 Storage and transport

All products should be stored in secure buildings, kept dry and out
of reach of children and animals, and separated from food and animal
feed. Containers should be sound and adequately labelled. Keep
containers well closed. Do not store near fertilizers, seeds,
insecticides, or fungicides. Storage vessels or tanks should not be
made of steel, galvanized steel, tin, or aluminium. Suitable
containers are high-density polyethylene bottles, resin-lined metal
drums, and glass containers.

4.5 Spillage

Keep spectators away from any leakage. Prevent contamination of
other goods or cargo, and of nearby vegetation and surface waters.
Absorb spillage of liquid products with earth or sand, sweep up, and
place in a separate container. Empty any product remaining in
damaged or leaking containers into a clean empty container, which
should be suitably labelled. Sweep up any spilt powder with damp
sawdust, taking care not to raise a dust cloud. Place in a separate
container for subsequent disposal. Contaminated absorbents, used
containers, surplus product, etc., should not be incinerated.

4.6 Disposal

Arsenic-containing wastes should not be buried in landfill sites,
except in very small quantities interspersed with large volumes of
non-hazardous wastes. Do not incinerate and do not discharge to
sewers or water courses.

Precipitation and/or solidification are preferred methods of
disposal, but should be undertaken by a specialist in toxic waste
disposal because of the persistence and toxicity of arsenic.

5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

The acute toxicities of dimethylarsinic acid and its salts for fish
are low. Methyl arsenic derivatives are phytotoxic. The long-term
effects on a number of non-target organisms are not known.
Biological transformations in soil result in the production of
more-toxic arsenic compounds, such as the volatile dimethyl- and
trimethylarsines, as well as inorganic arsenic.

6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

6.1 Previous evaluations by international bodies

The International Agency for Research on Cancer evaluated the
carcinogenic hazard of several organic arsenic compounds and
concluded that no adequate data on the carcinogenicity of organic
arsenic compounds are available.

WHO (1992) has classified dimethylarsinic acid and methanearsonic
acid as "slightly hazardous" pesticides with oral LD₅₀s for the rat
of 1350 mg/kg body weight and 1800 mg/kg body weight, respectively.
No acceptable daily intakes (ADI) for organic arsenic pesticides
have been established by the Joint FAO/WHO Meeting on Pesticide
Residues.

A guideline value of 0.05 mg As(total)/litre has been recommended in
the WHO publication, Guidelines for drinking-water quality.

6.2 Exposure limit values

In the USA, a time-weighted average of 0.5 mg/m³ has been
established for occupational exposure to organic arsenic compounds.

Residue limits of 0.7-2.8 mg/kg and 0.35-0.7 mg/kg, calculated as
As₂O₃, in food and feed have been established in the USA for
dimethylarsinic acid, and for the mono- and disodium salts of
methanearsonic acid, respectively.

Brazil has established tolerable limits of 0.2-0.7 mg/kg of
monosodium methanearsonate in specified plant products.

6.3 Specific restrictions

Argentina prohibits the use of monosodium methanearsonate in the
cultivation, commercial distribution, and industrial processing of
tobacco. Mixtures of dimethylarsinic acid and its sodium salt may
not be marketed in Portugal on account of their
environmental/toxicological effects.

In the USA, any solid waste (except domestic) containing
dimethylarsinic acid must be listed as hazardous waste, and is
subject to regulation and notification requirements, unless it is
found that the waste cannot pose a threat to human health or the
environment when improperly managed.

6.4 Transport and labelling

The United Nations Committee of Experts on the Transport of
Dangerous Goods has classified dimethylarsinic acid and its sodium
salt as "poisonous (toxic) substances". As such, strict regulations
have been applied to their transportation. The International
Maritime Dangerous Goods Code classifies such substances as marine
pollutants, and requires appropriate warning labels.

Canada classifies dimethylarsinic acid and its sodium salt as a
"toxic substance"; the maximum amount per package that may be
transported on a passenger aircraft, train, or road vehicle is 25
kg; the maximum amount per package that may be transported on a
cargo aircraft is 100 kg.

BIBLIOGRAPHY

IARC (1980) IARC monographs on the evaluation of carcinogenic risk
of chemicals to humans - some metals and metallic compounds. Vol.
23. Lyon, International Agency for Research on Cancer, pp. 39-41.

IRPTC (1987) IRPTC legal file 1986. Geneva, International Register
of Potentially Toxic Chemicals, United Nations Environment
Programme.

UNEP/IEO (1990) Storage of hazardous materials: a technical guide
for safe warehousing of hazardous materials. United Nations
Environment Programme, Industry and Environment Office, Paris, 80
pp.

UNITED NATIONS (1984) Consolidated list of products whose
consumption and/or sale have been banned, withdrawn, severely
restricted or not approved by governments. 1st ed. revised. New
York, United Nations.

UNITED NATIONS (1986) Recommendations on the transport of dangerous
goods. 4th ed. New York, United Nations.

WHO (1981) Environmental Health Criteria 18: Arsenic. Geneva, World
Health Organization, 174 pp.

WHO (1984) Guidelines for drinking-water quality. Vol. 1:
Recommendations. Geneva, World Health Organization, 130 pp.

WHO (1987) Air quality guidelines for Europe. Copenhagen, WHO
Regional Office for Europe, pp. 171-181 (European Series No. 23).

WHO (1989) Toxicological evaluation of certain food additives and
contaminants. Geneva, World Health Organization, pp. 155-162 (WHO
Food Additives Series 24).

WHO (1992) The WHO recommended classification of pesticides by
hazard and guidelines to classification 1992-1993. Geneva, World
Health Organization (unpublished document, WHO/PCS/92.14).

    See Also:
       Toxicological Abbreviations