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                         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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                        © World Health Organization 1994
    
    Publications of the World Health Organization enjoy copyright 
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    The designations employed and the presentation of the material in this 
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    the legal status of any country, territory, city or area or of its 
    authorities, or concerning the delimitation of its frontiers or 
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    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. 
     

       The Federal Minister for the Environment, Nature Conservation and
                      Nuclear Safety (Fed. Rel). Germany)
      provided financial support for, and undertook the printing of, this
                                  publication.

             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

    -----------------------------------------------------------------------------------------------------------------------------------
    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)