IPCS
Health and Safety Guide No. 87
CHLOROFORM
HEALTH AND SAFETY
GUIDE
This is a companion volume to
Environmental Health Criteria 163: Chloroform
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)
WORLD HEALTH ORGANIZATION, GENEVA 1994
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 Publicafion Data
Chloroform : health and safety guide.
(Health and safety guide ; no. 87)
1.Chloroform - adverse effects I.Series
ISBN 92 4 151087 0 (NLM Classification: QV 81)
ISSN 0259-7268
The World Health Organization welcomes requests for permission to
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Applications and enquiries should be addressed to the Office of
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© World Health Organization 1994
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provided financial support for, and undertook the printing of, this
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Computer typesetting by HEADS, Oxford OX8 8NY, England
Printed by Wissenschaftliche Verlagsgesellchaft mbH D-70009 Stuttgart 10
CONTENTS
INTRODUCTION...........................................
1. PRODUCT IDENTITY AND USES...........................
1.1 Identity.........................................
1.2 Physical and chemical properties.................
1.3 Composition......................................
1.4 Analysis.........................................
1.5 Production and uses..............................
2. SUMMARY AND EVALUATION..............................
3. CONCLUSIONS.........................................
4. HUMAN HEALTH HAZARDS, PREVENTION
AND PROTECTION, EMERGENCY ACTION...................
4.1 Human health hazards, prevention and
protection, first aid............................
4.2 Advice to physicians.............................
4.3 Health surveillance advice.......................
4.4 Explosion and fire hazards, prevention...........
4.4.1 Explosion and fire hazards................
4.4.2 Prevention................................
4.5 Storage..........................................
4.6 Transport........................................
4.7 Spillage.........................................
5. HAZARDS FOR THE ENVIRONMENT AND THEIR
PREVENTION..........................................
6. SUMMARY OF CHEMICAL SAFETY INFORMATION..............
7. CURRENT REGULATIONS, GUIDELINES, AND
STANDARDS...........................................
7.1 Exposure limit values............................
7.2 Specific restrictions............................
7.3 Labelling, packaging, and transport..............
7.4 Waste disposal...................................
BIBLIOGRAPHY...........................................
INTRODUCTION
The Environmental Health Criteria (EHC) monographs 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 ternis. 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 belpful 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
1. PRODUCT IDENTITY AND USES
1.1 Identity
Chemical formula: CHCL3
Chemical structure:
Figure1;;;grph87_1.bmp
Common name: chloroform
Common synonyms: trichloromethane, methane trichloride,
trichloroform, methyl trichloride, methenyl
trichloride
CAS registry 67-66-3
number:
RTECS registry FS 9100000
number:
Conversion factor: 1 ppm = 4.9 mg chloroform/m3 air 1 mg
chloroform/m3 air = 0.204 ppm at 25 °C and
101.3 kPa (760 mmHg).
1.2 Physical and Chemical Properties
Chloroform is a clear, colourless, very volatile liquid with a
characteristic odour and a burning sweet taste. Pure chloroform is
light sensitive, therefore reagent grade chloroform usually contains
0.75% ethanol as a stabilizer to avoid photochemical transformation to
phosgene and hydrogen chloride. The compound is soluble in most
organic solvents, but its solubility in water is limited (7.5-9.3
g/litre water at 25 °C).
The most important physical and chemical properties of chloroform are
presented in the Summary of Chemical Safety Information (page 19).
1.3 Composition
Technical-grade chloroform contains 0.5-1 % ethanol and its acidity is
maximally 0.002 % (as hydrogen chloride).
1.4 Analysis
Various sufficiently sensitive methods for determining chloroform in
air, water, and biological samples are available. The majority of the
methods are based on direct column injection or adsorption on activated
adsorbents followed by liquid, or thermal, desorption and subsequent
gas chromatographic analysis. For air and water detection limits of
0.01 µg/m3 and 1 µg/litre, respectively, could be achieved.
1.5 Production and Uses
Chloroform was widely used as an anaesthetic, but because of its toxic
effects, this use is being abandoned.
Chloroform is directly used in pesticide formulations, in drugs and
flavours, and it is used as a general laboratory reagent. Furthermore,
it is used as an intermediate, especially in the synthesis of
fluorocarbons, tetrafluoroethylene, and PTFE. The US-FDA banned the
use of chloroform as an ingredient in human drug and cosmetic products
in 1976. However, any drug product containing chloroform in residual
amounts is not considered to contain chloroform as an ingredient.
Currently, chloroform is manufactured by hydrochlorination of methanol
or by chlorination of methane. It can also be manufactured by oxy-
chlorination of methane. The production of chloroform has increased
over the years and in 1987 the world production was 440
kilotonnes/year.
2. SUMMARY AND EVALUATION
It is assumed that, because of its volatility, most chloroform present
in water is ultimately transferred to air. Chloroform has a residence
time in the atmosphere of several months. Chloroform is removed from
the atmosphere through chemical transformation. Chloroform is
resistant to biodegradation by the aerobic microbial populations of
soils and aquifers subsisting on endogenous substrates or supplemented
with acetate. Biodegradation may occur under anaerobic conditions.
Bioconcentration in freshwater fish is low. Depuration is rapid.
On the basis of estimates of mean exposures from various media, the
general population is exposed to chloroform principally in food,
drinking-water and indoor air in approximately equivalent amounts.
Estimated intake from outdoor air is considerably less. The total
estimated mean intake is approximately 2 µg/kg body weight per day.
Available data also indicate that water use in homes contributes
considerably to levels of chloroform in indoor air and to total
exposure. For some individuals living in dwellings supplied with tap
water containing relatively high concentrations of chloroform in
drinking-water, estimated total intakes are up to 10 µ/kg body weight
per day.
Chloroform is well absorbed in animals and humans after oral
administration but the absorption kinetics are dependent upon the
vehicle of delivery. After inhalation exposure of humans, 60-80% of
the quantity inhaled was absorbed. The primary factors affecting the
absorption kinetics of chloroform following inhalation are its
concentration and species-specific metabolic capacities. Chloroform is
readily absorbed through the skin of humans and animals and significant
dermal absorption of chloroform from water while showering has been
demonstrated. Hydration of skin apears to accelerate absorption of
chloroform.
Chloroform is distributed throughout the whole body. Highest tissue
levels are reached in the fat, blood, liver, kidneys, lungs, and
nervous system. Distribution is dependent on exposure route;
extrahepatic tissues receive a higher dose from inhaled or dermally
absorbed chloroform than from ingested chloroform. Placental transfer
of chloroform has been demonstrated in several animal species and
humans. Chloroform is eliminated primarily as exhaled carbon dioxide.
Unmetabolized chloroform is retained longer in fat than in any other
tissue.
The oxidative biotransformation of chloroform is catalyzed by the cyto-
chromes P450 to produce trichloromethanol. Loss of HCI from trichloro-
methanol produces phosgene as a reactive intermediate. Phosgene may be
detoxified by reaction with water to produce carbon dioxide or with
thiols including glutathione or cysteine to produce adducts. The
reaction of phosgene with tissue proteins is associated with cell
damage and death. Little binding of chloroform metabolites to DNA is
observed. Chloroform also undergoes cytochrome P450 catalyzed reductive
biotransformation to produce the dichloromethyl radical, which becomes
covalently bound to tissue lipids. A role for reductive
biotransformation in the cytotoxicity of chloroform has not been
established.
In animals and humans exposed to chloroform, carbon dioxide and
unchanged chloroform are eliminated in the expired air. The fraction
of the dose eliminated as carbon dioxide varies with the dose and the
species. The rate of biotransformation to carbon dioxide is higher in
rodent (hamster, mouse, rat) than in human hepatic and renal
microsomes, and chloroform is biotransformed more rapidly in mouse than
in rat renal microsomes.
The liver is the target organ for acute toxicity in rats and several
strains of mice. Liver damage is characterized mainly by early fatty
infiltration, and balloon cells, progressing to necrosis of the
centrilobular tissue and then massive necrosis. The keyney is the
target organ in male niece of other more sensitive strains. The
kidney damage begins with hydropic degeneration and progresses to
necrosis of the proximal tubules. Significant renal toxicity has not
been observed in female mice of any strain.
Acute toxicity varies, depending on the strain and sex of the animal
and the vehicle. In mice, the oral LD50 values ranged from 36 to 1366
mg chloroform/kg body weight. For rats, the LD50 values ranged from
450 to 2000 mg chloroform/kg body weight. After a single inhalation
exposure of 4 h, liver toxicity was observed in mice and rats at
chloroform levels of 490 mg/m3 and 1410 mg/m3.
The most universally observed toxic effect of chloroform is damage to
the liver. The severity of these effects per unit dose administered
depends on the species, and the vehicle and method by which the
chloroform is administered. The lowest dose at which liver damage has
been observed is 15 mg/kg body weight per day, administered to beagle
dogs in a toothpaste base over a period of 7.5 years. Effects at lower
doses were not examined. Higher doses are required to produce
hepatotoxic effects in other species. Though duration of exposure
varied in these studies, NOAELs ranged between 15 and 125 mg/kg body
weight per day.
Effects in the kidney have been observed in male mice of sensitive
strains and in the F344 rat. Severe effects have been observed in a
particularly sensitive strain of male mice at doses as low as 36 mg/kg
body weight per day.
Daily 6-h inhalation of chloroform, for 7 days consecutively, induced
atrophy of Bowman's glands and new bone growth in the nasal turbinates
of F-344 rats. The NOEL for these effects was 14.7 mg/m3. The
significance of these effects is being further investigated in longer-
term studies.
Chloroform induced hepatic tumours in mice, when administered by
gavage, in corn oil, at doses in the range of 138-477 mg/kg body weight
per day. However, when similar doses were administered in drinking-
water, there was no effect of chloroform on the yield of hepatic
tumours in niece. Moreover, when chloroform was administered to mice in
drinking-water, as a promoter in initiation/promotion studies, it
actually appeared to inhibit the development of diethylnitrosamine-
initiated liver tumours. Thus, the vehicle utilized and/or the method
in which chloroform is administered are an important variables in its
induction of hepatic tumours in mice.
Chloroform, administered in corn oil, by gavage, also induced kidney
tumours in rats at doses of 90-200 mg/kg body weight per day. However,
in this species, results were similar when the chen-tical was
administered in the drinking-water indicating that the response is not
entirely dependent on the vehicle use.
The carcinogenic effects of chloroform on the liver and kidneys of
rodents appear to be closely related to cytotoxic and cell replicative
effects observed in the target organs. The effects on cell replication
were found to parallel variations in carcinogenic responses to
chloroform, induced by vehicle and mode of administration. The weight
of the available evidence indicates that chloroform has little, if any,
capability of inducing gene mutation or other types of direct damage to
DNA. Moreover, chloroform does not appear capable of initiating
hepatic tumours in mice or of inducing unscheduled DNA synthesis in
vivo. On the other hand, hepatic tumours can be efficiently promoted
by chloroform when it is administered in an oil vehicle. Consequently,
it is likely that cytotoxicity, followed by the development of cell
proliferation with the prolonged administration of chloroform, is the
most important cause of liver and kidney tumours in rodents.
There are some limited data to suggest that chloroform is toxic for the
fetus, but only at doses that are maternally toxic.
In general, chloroform elicits the same symptoms of toxicity in humans
as in animals. Furthermore, in humans, anaesthesia may result in death
due to respiratory and cardiac arrhythmias and failure. Renal tubular
necrosis and renal disftmction have also been observed in humans. The
lowest levels at which liver toxicity due to occupational exposure to
chloroform has been reported are in the range of 80-160 mg/m3 , with an
exposure period of less than 4 months, in one study, and, in the range
of 10-1000 mg/m3, with exposure periods of 1-4 years, in another study.
The mean lethal oral dose for an adult is estimated to be about 45 g,
but large interindividual differences in susceptibility occur. Though
there is some weight of evidence, in epidemiological studies, for an
association between exposure to disinfection by-products in drinking-
water and colorectal and bladder cancer, they cannot be attributed to
chloroform, per se.
Chloroform is toxic for the embryo-larval stages of some amphibian and
fish species. The lowest reported LC50 was 0.3 mg/litre for the
embryo-larval stages of Hyla crucifer. Chloroform is less toxic for
fish and Daphnia magna. The LC50 values for several species of fish
were in the range of 18-191 mg/litre. There is little difference in
sensitivity between freshwater and marine fish. The lowest reported
LC50 for Daphnia magna was 29 mg/litre. The toxicity of chloroform
for algae and other microorganisms is low.
The Task Group concluded that available data are sufficient to develop
a tolerable intake for the non-neoplastic effects of chloroform and
risk-specific intakes for its carcinogenic effects, on the basis of
studies in animal species, to serve as guidance in the development of
exposure limits by appropriate authorities. However, it is cautioned
that, where local circumstances require that a choice must be made
between meeting microbiological limits or limits for disinfection by-
products, such as chloroform, the microbiological quality must always
take precedence. Efficient disinfection must never be compromised.
On the basis of the study by Heywood et al. (1979), in which slight
hepatotoxicity (increases in hepatic serum enzymes and fatty cysts) was
observed in beagle dogs ingesting 15 mg/kg body weight per day in
toothpaste for 7.5 years, and, incorporating an uncertainty factor of
1000 (x10 for interspecies variation, x 10 for intraspecies variation,
and x 10 for use of an effect level rather than a no-effect level and
a less than long-term study), a TDI of 15 µg/kg body weight per day was
obtained.
On the basis of the available mechanistic data, the approach considered
most appropriate for providing of guidance, based on mouse liver
tumours, was the division of a no-effect level for cell proliferation
by an uncertainty factor. On the basis of the NOEL for cytolethality
and cell proliferation in B6C3F1 mice of 10 mg/kg body weight per day,
following administration in corn oil for 3 weeks, in the study of
Larson et al. (1994), and, incorporating an uncertainty factor of 1000
( x 10 for interspecies variation, x 10 for intraspecies variation, and
x 10 for severity of effect, i.e., carcinogenicity), a TDI of 10 µg/kg
body weight per day was obtained.
It was recognized that the kidney tumours in rats may also be
associated with cell lethality and proliferation. However, as data on
cell proliferation were not available in the strain where tumours were
observed, and the identified information on cell proliferation and
lethality were concerned with short-term exposures (one single gavage
administration and 7-day inhalation exposure), it was considered
premature to deviate from the default model (i.e., linearized
multistage) as a basis for the estimation of lifetime cancer risk. The
total daily intake considered to be associated with a 10-5 excess
lifetime risk, based on the induction of renal tumours (adenomas and
adenocarcinomas) in male rats in the study by Jorgenson et al. (1985),
was 8.2 µg/kg body weight per day.
Levels of chloroform in surface waters are generally low and would not
be expected to present a hazard for aquatic organisms. However, higher
levels of chloroform in surface waters resulting from industrial
discharges or spills may be hazardous for the embryo-larval stages of
some aquatic species
3. CONCLUSIONS
The general population is expected to be exposed to predominantly low
levels of chloroform via air, drinking-water and food (total daily
uptake was estimated to be 2 µg/kg body weight ; see section 2).
Chloroform can affect reproduction and can be embryo/fetotoxic, but
not teratogenic. It is evident that chloroform can produce tumours in
the liver and kidneys in some strains of mice and rats after exposure
by gavage to dose levels that also produce toxic effects.
On the basis of the weight of evidence, it is suggested that chloroform
has no genotoxic properties, and that, because induced toxicity and
cell proliferation appear to be of major importance for its
carcinogenicity, chloroform can be considered as a compound with
carcinogenic properties for which there may be a threshold.
The carcinogenic risk for humans seems to be low. The daily human
uptake of chloroform (estimated to be 2 µg/kg body weight) is less than
the lowest calculated TDI of 8.2 µg/kg body weight as a 10-5 excess
lifetime risk, based on the induction of renal tumours in male rats
(see section 2). Higher daily intake could occur for certain
populations that are either occupationally exposed to, or live near,
potential sources of chloroform.
As chloroform will not remain in the water because of its high
volatility and low solubility, it will only present a risk, especially
for embryo-larval stages of several aquatic organisms, at times of
industrial discharges or spills.
4. HUMAN HEALTH HAZARDS, PREVENTION
AND PROTECTION, EMERGENCY RESPONSE
4.1 Human Health Hazards, Prevention and Protection, First Aid
The human health hazards associated with exposure to chloroform,
together with preventive and protective measures, and first-aid
recommendations, are listed in the Summary of Chemical Safety
Infomiation in section 6.
4.2 Advice to Physicians
If chloroform has been ingested or there has been great overexposure,
N-acetylcysteine should be used as an antidote to prevent chloroform-
induced hepatotoxicity. If exposed to chloroform vapours, the patient
should immediately be moved to fresh air (or given artifical
respiration) and kept under observation. Special attention should be
paid to the use of alcoholic beverages in combination with exposure to
chloroform, because they enhance the toxic effects of chloroform.
4.3 Health Surveillance Advice
Workers, including dental teams, frequently exposed to chloroform,
should be examined periodically and appropriate measures taken.
Preplacement and periodic examinations should include appropriate tests
for liver and kidney functions, and special attention should be given
to the nervous system, the skin, and to any history of alcoholism. In
all cases of accidental exposure, a medical practitioner should be
immediately consulted.
4.4 Explosion and Fire Hazards, Prevention
4.4.1 Explosion and fire hazards
Chloroform vapour is invisible, heavier than air, and spreads along the
ground. Chloroform is practically nonflammable, but it can liberate
phosgene when heated to high temperatures, or when involved in a fire.
However, the addition of small amounts, of any flammable compound or an
increase in oxygen content will make chloroform flammable.
Chloroform reacts violently with acetone or methanol, when in the
presence of alkali, and with perchloric acid in the presence of
phosphorus pentoxide, potassium- tert-butoxide, and sodium methylate.
Chloroform reacts explosively with sodium or sodium methoxide, in the
presence of methanol. It also reacts with metals (aluminium, sodium,
lithium, magnesium, potassium, iron, zinc) and nitrogen oxide.
4.4.2 Prevention
If large, closed containers of chloroform are exposed to heat or fire,
keep them cool by spraying with water.
Work with chloroform should be carried out under adequate ventilation
conditions. The breathing of vapours and skin contact should be
avoided. Protective clothing, masks, and gloves that provide a high
degree of chemical permeation resistance and eye protection should be
used.
4.5 Storage
Containers should be stored away from direct sunlight, since chloroform
slowly decomposes to oxidative products including phosgene. Chloroform
must be stored separately from oxidative compounds and strong bases,
and should not bestored in aluminium containers.
4.6 Transport
In case of accident, stop the engine. Notify the police and fire
brigade immediately, keep public away from the danger area, mark roads,
and wam other road users. Do not smoke, do not use naked lights, and
keep upwind.
In case of spillage or fire, follow advice given in sections 4.7 and
4.4, respectively. In case of poisoning, follow advice given in the
Summary of Chemical Safety Information (section 6).
4.7 Spillage
In case of spillage of chloroform, ensure personel protection
(protective clothing, safety goggles, rubber gloves, and respiratory
protective device) and carefully shut off leaks.
Adsorb the spilt chloroform in earth or sand and remove to safe place.
Prevent liquid from entering sewers, basements, or workpits, because
vapour may create a toxic atmosphere.
If chloroform has entered a water course or sewer, or if it has
contaminated soil or vegetation, wam police.
5. HAZARDS FOR THE ENVIRONMENT AND
THEIR PREVENTION
In view of the high toxicity of chloroform for embryo-larval stages of
some aquatic organisms, it may present a hazard for such organisms at,
or near, sites of industrial discharges or spills.
Contamination of the environment can be minimized by proper methods of
storage, handling, transport, and protection.
In case of spillage, apply the methods recommended in section 4.7.
6. SUMMARY OF CHEMICAL SAFETY
INFORMATION
This summary should be easily available to all health workers concerned
with, and users of, chloroform. It should be displayed at, or near,
entrances to areas where there is potential exposure to chloroform,
and on processing equipment and containers. The summary should be
translated into the appropriate language(s). All persons potentially
exposed to the chemical should also have the instructions in the
summary clearly explained.
Space is available for insertion of the National Occupational Exposure
Limit, the address atid telephone number of the National Poison
Control Centre, and local trade ntunes.
SUMMARY OF CHEMICAL SAFETY INFORMATION
CHLOROFORM
CHCl3
CAS Registry No. 67-66-3
-----------------------------------------------------------------------------------------------------------------------------------
PHYSICAL PROPERTIES OTHER CHARACTERISTICS
-----------------------------------------------------------------------------------------------------------------------------------
Melting point (°C) 63.2 Chloroform is a volatile, colourless liquid, with a characteristic
Boiling point (°C) 61.3 odour and a burning sweet taste; though nonflammable, it
Relative molecular mass 119.38 decomposes in fire or in heat, giving off toxic fumes (phosgene
Density (20°C) 1.484 and hydrochloric acid); because of its limited conductivity, vapour
Ignition temperature (°C) 1000 electrostatic charges may be generated through flow, movement,
Water solubility (25°C) 7.5-9.3 mg/litre etc.; chloroform reacts vigorously with acetone or methanol, in the
Vapour pressure (0°C) 8.13 kPa presence of alkali; it may react explosively with metals (aluminium,
Vapour pressure (20°C) 21.28 kPa magnesium, sodium, lithium, potassium, iron, zinc)
Vapour density (101.3 kPa; 0°C) 4.36 kg/m3
n-octanol-water partition
coefficient (log Pow) 1.97
Flash point none
Explosive limits none
-----------------------------------------------------------------------------------------------------------------------------------
HAZARD/SYMPTOM PREVENTION AND PROTECTION FIRST AID
-----------------------------------------------------------------------------------------------------------------------------------
SKIN: redness, it may cause defatting Wear protective gloves and clothing Remove contaminated clothing and wash
of the skin and chemical burns; it can skin with water and soap
de absorbed
EYES: redness, pain, blurred vision by Wear safety goggles or face shield in Wash the eyes with wateror neutral saline
splashing; stinging sensation by combination with breathing protection solution for at least 15 minutes; obtain
vapour medical attention
INHALATION: sore throat, coughing, Apply ventilation, exhaust hood, or Remove victim to fresh air and keep
vomiting, pulmonary oedema, giddiness, breathing protection quiet; obtain medical attention or,
nausea, headache, unconsciousness, and necessary, move to hospital
cardiac arrythmias; signs of liver and
kidney injury
INGESTION: corrosive; confusion diarrhoea, Do not eat, drink, chew, or smoke Rinse mouth; do not induce vomiting,
vomiting; same systemic symptoms as those during work; do not keep food in areas allow victim to drink water and move
following inhalation with potential exposure; keep out of immediately to hospital
reach of children
ENVIRONMENTAL: may present a hazard to Minimize contamination of water, soil,
embryo-larval stages of some aquatic and atmosphere by proper methods of
organisms at points of discharge or spills storage, handling, transport, and waste
disposal
-----------------------------------------------------------------------------------------------------------------------------------
SPILLAGE STORAGE FIRE AND EXPLOSION
-----------------------------------------------------------------------------------------------------------------------------------
Ensure personnal protection; shut off Store separately from oxidative All kinds of extinguishing agents are
leaks, if without risk; collective leaking substances or strong bases; do not allowed, when there is a fire in the
liquid in closed containers; absorb split store in aluminium containers; keep immediate vicinity; when in a fire, keep
chloroform in earth or sand and remove to away from direct sunlight containers cool
a safe place; prevent entry into sewers
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WASTE DISPOSAL NATIONAL INFORMATION
-----------------------------------------------------------------------------------------------------------------------------------
Dissolve in a combustible fuel, National occupational exposure limit:
such as kerosene and incinerate with care
National Poison Control Centre:
7. CURRENT REGULATIONS, GUIDELINES,
AND STANDARDS
The information in this section has been extracted from the
Intemational Register of Potentially Toxic Chemicals (IRPTC) legal
file. Its intention is to give the reader an 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.
7.1 Exposure Limit Values
Some exposure limit values are given in the table on pages 24-25.
When no effective date appears in the IRPTC legal file, the year of the
reference from which the data are taken is indicated by (r).
7.2 Specific Restrictions
Canada
In Canada it is prohibited to sell, advertise, or import polishes,
cleaning agents, liquid coating materials, and paint or varnish
removers containing chloroform, when packaged as consumer products,
unless detailed labelling requirements have been satisfied (Effective
date: 1978).
7.3 Labelling, Packaging, and Transport
Canada
The maximum amount per package that may be transported on a passenger
aircraft, train, or road vehicle is 5 litres. Maximum amount per
package that niay be transported on a cargo aircraft is 60 litres
(Effective date: 1987).
EEC
Chloroform is considered to be a harmful substance. Member states
should ensure that dangerous preparations (solvents) are not placed on
the market
CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
EXPOSURE LIMIT VALUES
----------------------------------------------------------------------------------------------------------------------
Medium Specification Country/ Exposure limit description Value Effective
organization date
----------------------------------------------------------------------------------------------------------------------
AIR Occupational Australia Threshold limit value (TLV) 1985 (r)
Time-weighted average (TWA) 50 mg/m3
Short-term exposure limit (STEL) 225 mg/m3
Belgium Threshold limit value (TLV) 1989 (r)
Time-weighted average (TWA) 50 mg/m3
Canada Threshold limit value (TLV) 1980
Time-weighted average (TWA) 50 mg/m3
Finland Maximium permissible concentration
Time-weighted average (TWA) 50 mg/m3 1989 (r)
Short-term exposure limit (STEL) (15-min) 100 mg/m3 1993 (r)
Hungary Maximium permissible concentration 1985 (r)
Time-weighted average (TWA) 20 mg/m3
Short-term exposure limit (STEL) (30-min) 100 mg/m3
Italy Threshold limit value (TLV) 50 mg/m3 1985 (r)
Japan Maximium permissible concentration 1988 (r)
Time-weighted average (TWA) 240 mg/m3
The Netherlands Maximium limit (MXL)
Time-weighted average (TWA) 50 mg/m3 1987 (r)
----------------------------------------------------------------------------------------------------------------------
Medium Specification Country/ Exposure limit description Value Effective
organization date
----------------------------------------------------------------------------------------------------------------------
AIR Occupational Poland Maximium permissible concentration
Time-weighted average (TWA) 50 mg/m3 1985 (r)
Romania Maximium permissible concentration
Time-weighted average (TWA) 150 mg/m3 1985 (r)
Sweeden Hygienic limit value (HLV) 1988
Time-weighted average (TWA) 10 mg/m3
Short-term exposure limit (15-min. TWA) 25 mg/m3
United Kingdom Time-weighted average (TWA) 50 mg/m3 1987 (r)
Short-term exposure limit (STEL)
(10-min TWA) 225 mg/m3
USA/ACGIH Threshold limit value (TLV) 1993
Time-weighted average (TWA) 50 mg/m3
USA/OSHA Permissible exposure limit (PEL) 1974
Ceiling limit value (CLV) 240 mg/m3
USA/NIOSH Recommendation short-term exposure 1977
limit (STEL) (60-min) 9.78 mg/m3
unless their packages, fastenings, and labels comply with the EEC
requirements (Effective date: 1984).
Japan
Chloroform is designated as deleterious by law (Effective date: 1950).
United Kingdom
Labelling of road tankers: toxic substance (Effective date: 1979).
7.4 Waste Disposal
USA
When chloroform is a commercial chemical, it is identified in the USA
as a "toxic waste", subject to handling, transport, treatment, storage,
and disposal regulation and permit and notification requirements. Any
solid waste (except domestic) containing chloroform, must be listed as
a hazard waste (subject to handling, transport, treatment, storage, and
disposal regulation and permit and notification requirements), unless
the waste cannot pose a threat to human health or environment when
improperly managed (Effective date: 1980).
BIBLIOGRAPHY
CEFIC (1979) Transport emergency cards for individual products.
Chemical Industries Association Ltd.
Chemical cards (1992) Data for working safely with chemicals, 8th
edition. The Dutch Institute for the working place circumstances
(NIA), The Association of the Dutch Chemical Industry (VNCI), Samson HD
Tjeenk Willinkk [In Dutch].
Flanagan RJ & Meredith TJ (1991) Use of N-acetylcysteine in clinical
toxicology. Am J Med 91(suppl. 3C): 13IS-139S.
Heywood R, Sortwell RJ, Noel PRB, Street AE, Prentice DE, Roe FJC,
Wardsworth PF, Worden AN & Van Abbé NJ (1979) Safety evalution of
toothpaste containing chloroform. III. Long-term study in beagle dogs.
J Environ Pathol Toxicol 2:835-851.
IARC (1979) IARC Monographs on the evaluation of carcinogenic risk of
chemicals to humans, Vol. 20: Some halogenated hydrocarbons.
IRPTC Data Profile (legal file) on chloroform (March 1991).
Jorgenson TA, Meierhenry EF, Rushbrook CJ, Bull RJ & Robinson M (1985)
Carcinogenicity of chloroform in drinking water to male Osbome-Mendel
rats and female B6C3FI mice. Fundam Appl Toxicol 5:760-769.
Larson JL, Wolf DC & Butterworth BE (1994) Induced cytotoxicity and
cell proliferation in the hepatocarcinogenicity of chloroform in female
B6C3FI mice. Comparison of administration by gavage in com oil vs, ad
libitum in drinking water. Fundam Appl Toxicol 22:90-102.
Sax NI & Lewis RJ (1987) Hazardous chemicals desk reference. New York,
Van Nostrand Reinhold Company.
Sax NI & Lewis RJ (1989) Dangerous Properties of Industrial Materials,
7th edition. New York, Van Nostrand Reinhold Company.
Sittig M (1979) Hazardous and toxic effects of industrial chemicals.
Park Ridge, New Jersey, USA, Noyes Data Corporation.
Walsh D (1988) Chemical safety data sheets, Vol. 1. London, Royal
Society of Chemistry.
WHO (1994) Environmental Health Criteria 163: Chloroform. Geneva,
World Health Organization.
See Also:
Toxicological Abbreviations
Chloroform (EHC 163, 1994)
Chloroform (ICSC)
Chloroform (WHO Food Additives Series 14)
CHLOROFORM (JECFA Evaluation)
Chloroform (PIM 121)
Chloroform (CICADS 58, 2004)
Chloroform (IARC Summary & Evaluation, Supplement7, 1987)
Chloroform (IARC Summary & Evaluation, Volume 1, 1972)
Chloroform (IARC Summary & Evaluation, Volume 20, 1979)
Chloroform (IARC Summary & Evaluation, Volume 73, 1999)