IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 61
ISOBENZAN
HEALTH AND SAFETY GUIDE
UNITED NATIONS ENVIRONMENT PROGRAMME
INTERNATIONAL LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
WORLD HEALTH ORGANIZATION, GENEVA 1991
This is a companion volume to Environmental Health Criteria 129:
Isobenzan
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
Isobenzan : health and safety guide.
(Health and safety guide ; no. 61)
1. Insecticides, Organochlorine - standards
2. Insecticides, Organochlorine - toxicity
3. Hazardous substances I. Series
ISBN 92 4 151061 7 (NLM Classification: WA 240)
ISSN 0259-7268
(c) World Health Organization 1991
Publications of the World Health Organization enjoy copyright
protection in accordance with the provisions of Protocol 2 of the
Universal Copyright Convention. For rights of reproduction or
translation of WHO publications, in part or in toto, application
should be made to the Office of Publications, World Health
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welcomes such applications.
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publication do not imply the expression of any opinion whatsoever on
the part of the Secretariat of the World Health Organization
concerning the legal status of any country, territory, city or area or
of its authorities, or concerning the delimitation of its frontiers or
boundaries.
The mention of specific companies or of certain manufacturers'
products does not imply that they are endorsed or recommended by the
World Health Organization in preference to others of a similar nature
that are not mentioned. Errors and omissions excepted, the names of
proprietary products are distinguished by initial capital letters.
CONTENTS
INTRODUCTION
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
3. CONCLUSIONS AND RECOMMENDATIONS
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1. Main human health hazards, prevention and protection,
first aid
4.1.1. Symptoms of poisoning
4.1.2. Medical advice
4.1.3. Health surveillance advice
4.2. Explosion and fire hazards
4.2.1. Explosion hazard
4.2.2. Fire hazard
4.3. Storage
4.4. Transport
4.5. Spillage and disposal
4.5.1. Spillage
4.5.2. 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. Labelling, packaging, and transport
6.5. Waste disposal
6.6. Other measures
BIBLIOGRAPHY
INTRODUCTION
The Environmental Health Criteria (EHC) documents produced by the
International Programme on Chemical Safety include an assessment of
the effects on the environment and on human health of exposure to a
chemical or combination of chemicals, or physical or biological
agents. They also provide guidelines for setting exposure limits.
The purpose of a Health and Safety Guide is to facilitate the
application of these guidelines in national chemical safety
programmes. The first three sections of a Health and Safety Guide
highlight the relevant technical information in the corresponding EHC.
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. Within the Guide is a Summary of Chemical Safety
Information which should be readily available, and should be clearly
explained, to all who could come into contact with the chemical. 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. A bibliography has been included for
readers who require further background information.
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 Manager
International Programme on Chemical Safety
Division of Environmental Health
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
1. PRODUCT IDENTITY AND USES
1.1 Identity
Common name: Isobenzan
Molecular formula: C9H4Cl8O
Chemical structure:
Chemical names: 1,3,4,5,6,7,8,8-octachloro-4,7-methylene-
3a,4,7,7a-tetrahydro-isobenzofuran;
1,3,4,5,6,7,8,8-octachloro-3a,4,7,7a-tetra-
hydro-4,7-endomethylene-naphthalene (IUPAC)
Developmental codes: BAS-4402; CP 14957; ENT-25545; OMS-206;
OMS-618; SD-4402, WL 1650
Trade names: Telodrin (technical product), Omtan
Purity (technical): not less than 95% (w/w)
CAS registry number: 297-78-9
Conversion factors: 1 ppm = 17 mg/m3 at 20°C
1 mg/m3 = 0.06 ppm at 20°C
RTECS registry number: PC1225000
1.2 Physical and Chemical Properties
Isobenzan is a whitish to light-brown crystalline powder, with a mild
chemical odour. It is relatively stable to acids, but liable to
dehydrochlorination under strongly alkaline conditions.
Some physical properties of isobenzan are given in Table 1.
Table 1. Physical properties
Relative molecular mass 411.73
Melting point (°C) 120-122
Flash-point non-flammable
Explosion limits non-explosive
Specific gravity 1.87
Vapour pressure (20°C) 6.7 x 10-4 Pa (5 x 10-6 mmHg)
Solubility in water practically insoluble
Solubility in organic solvents: slightly soluble in kerosene and
ethanol; soluble in acetone, benzene, toluene, xylene, heavy aromatic
naphtha, and ethyl ether.
1.3 Analytical Methods
The method of choice is gas-liquid chromatography with
electron-capture detection.
1.4 Production and Uses
Isobenzan is a broad spectrum contact and stomach insecticide, which
was manufactured from 1958 to 1965 and was used throughout the world.
Its agricultural use was restricted, because of its persistence and
toxicity.
2. SUMMARY AND EVALUATION
As far as is known, isobenzan, an organochlorine insecticide, was only
manufactured during the period 1958-65. Existing stocks were used for
several years after this. At present, the only major sources of
exposure are believed to be the original waste-disposal sites of
industrial wastes, and dredgings from contaminated sediments.
Following the application of isobenzan to the soil, a rapid initial
loss occurs, after which the remaining compound decays at a much
slower rate. Isobenzan persists in the soil from 2 to 7 years,
depending on the type of soil. Under laboratory conditions, isobenzan
decomposes in surface water within a few weeks, when exposed to
natural and artificial light.
Soil, ground water, and surface water from polders built up using
sediment contaminated with organochlorines, including chlorinated
cyclodiene compounds, still contained minor residues of isobenzan some
years later. Sediments of rivers in the Netherlands did not contain
any detectable isobenzan (less than 0.01 mg/kg dry weight). Crop
residues, resulting from soil treatment, are usually low (below
0.05 mg/kg crop), but higher levels may be found in some root crops
(up to 0.2 mg/kg in carrots). No residues were detected (less than
0.01 mg/kg) in food items analysed in market surveys that were carried
out when isobenzan was being used in agriculture.
When domestic animals were introduced to pastures treated with
isobenzan, the dairy products contained residues of the compound. Two
samples of butter contained 0.07-0.15 mg isobenzan/kg product. In
milk, the levels were 0.005-0.07 mg/kg (whole milk). Dried milk
contained only 0.005 mg/kg. Up to 50% of the residue was lost during
the processing of dairy products, depending on the type of treatment.
No data were available on the levels of isobenzan in the blood and
adipose tissue of the general population. Operators of manufacturing
and formulation plants exposed to isobenzan had mean whole blood
levels of isobenzan of up to 0.041 mg/litre. In whole blood samples
from people living in the neighbourhood of one plant, the
concentration of isobenzan was below the limit of detection of
0.001 mg/litre.
Isobenzan is well absorbed through the gastrointestinal wall. It is
transported in the blood as the unchanged compound. Hydrophilic
metabolites are formed, one of which has been identified as isobenzan
lactone. Isobenzan accumulates in the tissues and organs of rats and
dogs in the following order: fat > liver = muscle > brain > blood.
In general, the concentrations are higher in the tissues of female
rats than in those of male rats, especially in the body fat. The
biological half-life in the body fat was 10.9 days in male rats and
16.6 days in female rats. A female dog pup that had fed only on its
mother's milk (containing 0.7 mg/litre of whole milk) showed
convulsions 15 days after birth. The blood of the pup contained
0.09 mg/litre. These effects in the pup were also seen in a rat
reproduction study. Isobenzan is excreted via the milk of cows.
Mosquito larvae and soil fungi metabolize isobenzan in the same way as
vertebrates, yielding isobenzan-lactone.
Isobenzan is very persistent in the environment and bioaccumulates.
It is highly toxic for fish, shrimps, and birds. In the Netherlands,
the country where isobenzan was produced, residues in the eggs of
terns living along the Dutch coast ranged up to 0.45 mg/kg (mean,
0.09 mg/kg); mean residues in mussels and fish were 0.05 mg/kg in
1965. Earthworm numbers were reduced in field plots treated with
isobenzan at 2 kg/ha. Nitrification was reduced, with a consequent
increase in inorganic nitrogen, in soils treated with isobenzan in the
field at 1 kg/ha; laboratory studies did not show any effects on
nitrification at doses equivalent to 250 g/ha.
The acute toxicity of isobenzan is high in mammals exposed via the
oral or percutaneous route. The mode of action is an overstimulation
of the central nervous system, resulting in convulsions. The acute
toxicity of formulations of isobenzan varies according to the
percentage of active ingredient present.
Isobenzan is not a skin irritant, but some formulations may cause
irritation.
Limited short- and long-term oral studies on mice, rats, and dogs have
been carried out. Isobenzan may cause histological changes in the
liver of the classical type associated with organochlorine
intoxication. In a long-term rat study, a no-observed-effect level
(NOEL) of 5 mg/kg diet (ca 0.25 mg/kg body weight) was found. In a
2-year study on dogs, a NOEL of 0.025 mg/kg body weight was
established.
A one-generation reproduction study on rats indicated a NOEL of
0.1 mg/kg diet (ca 0.005 mg/kg body weight). A higher dose level of
1 mg/kg diet (ca 0.05 mg/kg body weight) decreased survival of pups.
No teratogenicity or mutagenicity studies have been reported.
No carcinogenic potential was demonstrated in a 2-year oral study on
rats and an oral study on mice; both these studies were inadequate for
the evaluation of carcinogenicity.
The toxicological data base for isobenzan is incomplete. The Task
Group considered that the quality of the data was generally poor, by
today's standards, and that the data were inadequate to make an
evaluation of the hazards of isobenzan for human health or for the
environment.
Data on exposed human beings are limited to observations on workers in
a factory in the Netherlands during the manufacture and formulation of
isobenzan and related "drins". No cases of skin irritation were
reported. Convulsions occurred in several cases of intoxication, but
the changes in the EEG pattern were reversible. The intoxication
threshold level (for convulsions) was estimated to be 0.015 mg
isobenzan/litre blood. The biological half-life of isobenzan in human
blood was estimated to be of the order of 2.8 years.
3. CONCLUSIONS AND RECOMMENDATIONS
Isobenzan is highly toxic and very persistent. The available
information on the hazards of isobenzan is incomplete. However,
available data are sufficient to indicate that the hazards posed to
those handling isobenzan, and to the environment, are such that any
human or environmental exposure to this substance, either as an
insecticide or for any other purpose, should not be allowed.
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1 Main Human Health Hazards, Prevention and Protection, First Aid
Isobenzan is an organochlorine insecticide. It is highly toxic (rat
oral LD50: 5-10 mg/kg) and can be very hazardous for human beings if
incorrectly or carelessly handled. It is therefore essential that the
correct precautions should be observed in its handling and use.
The human health hazards of isobenzan exposure, together with
preventive and protective measures and first aid, are listed in
Table 2.
4.1.1 Symptoms of poisoning
Isobenzan is readily absorbed by mouth, by skin contact (especially
liquid formulations), and by inhalation (especially dust or mist). It
acts as a stimulant of the central nervous system. It is eliminated
from the body very slowly.
Following accidental ingestion or gross overexposure, symptoms may
include headache, dizziness, nausea, vomiting, weakness in legs, and
convulsions.
Respiratory depression may lead to metabolic acidosis and, if
necessary, blood gases should be checked. The use of an ECG monitor
is recommended, if the symptoms are severe.
4.1.2 Medical advice
Medical treatment is largely symptomatic and supportive, and directed
against convulsions and hypoxia.
If isobenzan is swallowed, the stomach should be emptied as soon as
possible by careful gastric lavage (with a cuffed endotracheal tube
already in place), avoiding aspiration into the lungs. In a rural
situation, where this is not feasible, and if the victim is conscious,
vomiting should be induced immediately. This should be followed by
intragastric administration of 50 g of activated charcoal and 30 g
magnesium or sodium sulfate in a 30% aqueous solution. Oily
purgatives are contraindicated. No fats, oils, or milk should be
given.
TABLE 2. HUMAN HEALTH HAZARDS, PREVENTIVE AND PROTECTIVE MEASURES, AND FIRST AID
HAZARDS/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
SKIN: may cause poisoning in Avoid contact with skin; wear After contact with skin, wash immediately
contact with skin suitable impervious protective with plenty of water and soap; remove all
clothing and gloves contaminated clothing immediately, and
launder separately before re-use
EYES: may cause irritation to Avoid contact with eyes; wear In case of contact with eyes, rinse
eyes eye protection immediately with plenty of water and seek
medical advice
INHALATION: dusts may cause Wear appropriate dust mask or
poisoning by inhalation respirator
INGESTION: unlikely occupational Do not eat, drink, or smoke during
hazard work; wash hands before eating,
drinking, or smoking
Accidental or intentional ingestion If swallowed, seek medical advice
may cause poisoning immediately and show container or label;
keep at rest, and ensure a clear airway;
if, in a rural situation, gastric lavage is
not possible, and the victim is
conscious, induce vomiting
If convulsions occur, anti-convulsants should be given immediately,
e.g., 10 mg of diazepam, slowly, intravenously (children 1-5 mg),
repeated as necessary; or thiopental sodium or hexobarbital sodium
slowly, intravenously, in a dose of 10 mg/kg with a maximum total dose
of up to 750 mg for an adult, or paraldehyde 5 ml by intramuscular
injection. These short-acting anticonvulsants should always be
followed by phenobarbital given orally at 3 mg/kg (up to 200 mg for an
adult), or phenobarbital sodium given intramuscularly at 3 mg/kg (also
up to 200 mg for an adult).
Morphine and its derivatives, adrenaline, and noradrenaline should
never be given.
An unobstructed airway must be maintained. Respiratory inadequacy,
which may be accentuated by barbiturate anticonvulsants, should be
corrected; oxygen and/or artificial ventilation may be needed.
4.1.3 Health surveillance advice
A complete medical history and physical examination of regularly
exposed workers should be made, on an annual basis.
4.2 Explosion and Fire Hazards
4.2.1 Explosion hazard
The explosion hazard will depend on the solvent used in the
formulation, or on the characteristics of the dust.
4.2.2 Fire hazard
Liquid formulations containing organic solvents may be flammable.
Extinguish fires with alcohol-resistant foam, carbon dioxide, or
powder. With sufficient burning or external heat, isobenzan will
decompose, emitting toxic fumes. Fire-fighters should be equipped
with self-contained breathing apparatus, eye protection, and full
protective clothing.
The use of water spray should be confined to the cooling of unaffected
containers, thus avoiding the accumulation of polluted run-off from
the site.
4.3 Storage
Products should be stored in locked buildings, preferably dedicated to
insecticides, and in compliance with labelling recommendations.
Keep the products out of reach of children and unauthorized personnel.
Do not store near foodstuffs or animal feed.
4.4 Transport
Comply with any national or local requirements regarding movement of
hazardous goods or wastes. Do not transport in the same compartment
as foodstuffs or animal feed. Check that containers are sound, and
labels undamaged, before dispatch.
4.5 Spillage and Disposal
4.5.1 Spillage
Before dealing with any spillage, precautions should be taken as
required, and appropriate personal protection should be used
(Table 2). Empty any product remaining in a damaged or leaking
container into a clean empty drum, which should then be tightly closed
and suitably labelled.
Prevent liquid from spreading or contaminating other cargo and
vegetation, and avoid pollution of surface waters and ground water by
using the most suitable available material, e.g., earth or sand.
After emptying, leaking containers should be rinsed with at least
1 litre water per 20-litre drum. Swirl round to rinse the walls of
the container, empty, and add the rinsings to the sawdust or earth.
Puncture or crush the container to prevent re-use.
As soon as possible after the spillage, and before re-use, cover all
contaminated areas with damp sawdust, sand, or earth. Sweep up and
place in a closeable container for later transfer to a safe place for
disposal.
4.5.2 Disposal
Any surplus product, contaminated absorbents, and containers should be
disposed of in an appropriate way. Waste material should be burned in
a proper incinerator designed for organochlorine waste disposal, with
effluent gas scrubbing. If this is not possible, bury in an approved
dump or landfill where there is no risk of contamination of surface or
ground water. Comply with any local requirements regarding disposal
of toxic wastes. Puncture or crush container to prevent re-use.
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
Isobenzan is very persistent in the environment and in biota. It is
highly toxic for aquatic and terrestrial organisms.
Discharges from the manufacture, formulation, or use of isobenzan, and
any spillage or unused product, must be prevented from spreading to
vegetation or waterways, and must be treated and disposed of properly
(section 4.5.2).
6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
The information given in this section has been extracted from the
International Register of Potentially Toxic Chemicals (IRPTC) legal
file and other United Nations sources. Its intention is to give the
reader a representative, but not an exhaustive, overview of current
regulations, guidelines, and standards.
The reader should be aware that regulatory decisions about chemicals,
taken in a certain country, can only be fully understood in the
framework of the legislation of that country. Furthermore, the
regulations and guidelines of all countries are subject to change and
should always be verified with the appropriate regulatory authorities
before application.
6.1 Previous Evaluations by International Bodies
Not available.
6.2 Exposure Limit Values
No data available.
6.3 Specific Restrictions
In the Federal Republic of Germany, isobenzan has been prohibited for
use as a plant protectant. It has not been registered as a pesticide
in, among others, Canada, the Netherlands, Sweden, the United Kingdom,
and the USA (where it had previous approval for use on alfalfa, corn,
and tobacco).
6.4 Labelling, Packaging, and Transport
The United Nations Committee of Experts on the Transportation of
Dangerous Goods classifies isobenzan in:
Hazard Class 6.1: poisonous substance;
Packing Group I: substances and preparations presenting a very
severe risk of poisoning, when the content of
active ingredient is 10-100%;
Packing Group II: substances and preparations presenting a
serious risk of poisoning, when the content
of active ingredient is 2-10%;
Packing Group III: substance presenting a relatively low risk of
poisoning in transport, when the content of
active ingredient is 0.4-2%.
The labels should be as follows:
The European Economic Community legislation requires labelling as a
dangerous substance using the symbol:
The label must read:
Very toxic by inhalation, in contact with skin and if swallowed;
irritating to eyes and skin; keep locked up; keep away from
food, drink and animal feeding stuffs; if you feel unwell, seek
medical advice (show the label where possible).
The European Economic Community legislation on the labelling of
pesticide preparations classifies isobenzan in Class 1A for the
purpose of determining the label for preparations containing isobenzan
and other active ingredients.
6.5 Waste Disposal
No information is available.
6.6 Other Measures
The European Economic Community legislation concerning the major
accident hazards of certain industrial activities foresees that the
manufacturer must take all necessary measures to prevent accidents and
to limit their consequences for man and the environment, when
processing isobenzan in quantities equal to or over 100 kg.
Notification must be made to the competent authorities, giving
information on the substance, the installation, information on
possible major accident situations, and emergency plans.
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