1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names, main trade names
   1.6 Main manufacturers, main importers
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles.
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous characteristics
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
   7.1 Mode of Action
   7.2 Toxicity
      7.2.1 Human data Adults Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI) and other guideline levels
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
   8.2 Toxicological Analyses and their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material Simple Qualitative Test(s) Advanced Qualitative Confirmation Test(s) Simple Quantitative Method(s) Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens Simple Qualitative Test(s) Advanced Qualitative Confirmation Test(s) Simple Quantitative Method(s) Advanced Quantitative Method(s) Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis Blood, plasma or serum Urine Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
   8.6 References
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological Central Nervous System (CNS) Peripheral nervous system Autonomic nervous system Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary Renal Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic Acid-base disturbances Fluid and electrolyte disturbances Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
   10.1 General principles
   10.2 Life supportive procedures and symptomatic treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
   11.1 Case reports from literature
   12.1 Specific preventive measures
   12.2 Other

    International Programme on Chemical Safety
    Poisons Information Monograph 121

    1.  NAME

        1.1  Substance


        1.2  Group

             Organochlorine solvent

        1.3  Synonyms

             chloroform (Dutch, German, Polish),
             chloroform (IUPAC),
             chloroforme (French),
             chloroformium anaestheticum,
             chloroformum pro narcosi,
             formyl trichloride,
             methane trichloride,
             methenyl chloride,
             methenyl trichloride,
             methyl trichloride,
             trichloormethaan (Dutch),
             trichlormethan (Czech),
             triclorometano (Italian),

        1.4  Identification numbers

             1.4.1  CAS number


             1.4.2  Other numbers

                    1888 (UN)
                    FS9100000 (NIOSH)
                    UN Hazard class: 6.1 (poisonous substances)

        1.5  Main brand names, main trade names

             Freon 20, NCI-C02686, R20, R20 (refrigerant)

        1.6  Main manufacturers, main importers

             Produced by many manufacturers and widely

    2.  SUMMARY

        2.1  Main risks and target organs

             Acutely, CNS depression and respiratory arrest; late
             onset liver and kidney damage.

        2.2  Summary of clinical effects

             Acute poisoning with chloroform is uncommon. The main
             route of exposure is inhalation but in some cases poisoning
             is due to ingestion; skin absorption is limited. Central
             nervous system depression is the most prominent sign after
             acute exposure. Death may occur within few minutes of heavy
             exposure from respiratory arrest or from  ventricular
             fibrillation (cardiac arrest). The prognosis is favourable if
             consciousness is recovered but liver and kidney damage may
             then develop. Less severe exposure causes dizziness, dilated
             pupils, nausea, vomiting.

        2.3  Diagnosis

             Headache, impaired consciousness, convulsions,
             respiratory paralysis, dizziness, abdominal pain, nausea,
             vomiting and diarrhoea are the feature of chloroform
             poisoning following ingestion There may be dizziness and
             short of breath following inhalation.
             Later, symptoms of liver and kidney may develop. The main
             features of acute poisoning do not depend on the route of
             entry  but rather on the amount of chloroform absorbed by the
             Analysis of biological fluids plays no role in the diagnosis
             of acute poisoning.

        2.4  First-aid measures and management principles.

             Management consists of early decontamination, supportive
             treatment with respiratory and cardiac monitoring, avoidance
             of catecholamine drugs and treatment of hepatic and or kidney
             failure if they occur.


        3.1  Origin of the substance

             Although negligible amounts of chloroform may be
             produced naturally in the atmosphere (Ross et al., 1978) and
             in soil and water (Clayton & Clayton, 1981), manufacturing is
             the main source.
             Chloroform is usually manufactured by two processes -
             hydrochlorination and then further chlorination of methanol
             or chlorination of methane (GCA Corporation, 1984).  Both
             processes yield a mixture of chloromethanes.  Chloroform is
             then separated by sequential distillation.

        3.2  Chemical structure

             Molecular weight 113.4

        3.3  Physical properties

             3.3.1  Colour

             3.3.2  State/Form

             3.3.3  Description

                    Boiling point: 61.15C - 61.70C.
                    Melting point: -63.2 - -63.5C at atmospheric
                    Flash point:  none.
                    Relative vapour density (air = 1): 4.1 - 4.36 kg/m at
                    101 kPa, 0C. 
                    Vapour pressure:        21.15 kPa at 20C.
                    Solubility in water:    10.62g/kg at OC
                                            8.95g/kg at 10C
                                            8.22g/kg at 20C
                    Specific gravity:       1.483 at 20C
                    Chloroform is miscible with acetone, benzene, carbon
                    disulphide, carbon tetrachloride, ethanol, ether,
                    petroleum ether, fixed and volatile oils and most
                    organic solvents.
                    Concentration Conversion Factors
                    1 mg/l = 206 ppm 1 ppm = 4.89 mg/m3 at 25C and
                    atmospheric pressure (Royal Society of Chemistry,

        3.4  Hazardous characteristics

             At normal temperature and pressures, chloroform is a
             heavy, very volatile, clear, colourless, highly refractive,
             non inflammable liquid.  It has a characteristic sweet,
             ethereal odour and a sweetish burning taste. The odour is not
             irritant. Pure chloroform is light, sensitive and reagent
             grade chloroform usually contains 0.75% ethanol as stabilizer 
             Chloroform reacts vigorously with acetone in the presence of
             KOH or CaOH. It may also react explosively with fluorine,
             dinitrogen tetraoxide, aluminium, lithium, sodium,
             sodium/methanol, NaOH/methanol, sodium methoxide and
             triisopropylphosphine (Sax, 1984; Bretherick, 1979). 
             Mixtures of chloroform and nitromethane  are said to be
             detonable (Bretherick, 1979).
             Chloroform is oxidized by strong oxidizing agents such as
             chromic acid with formation of phosgene and chlorine gas.
             Chloroform  may generate the highly toxic gas phosgene if it
             comes into contact with flames or hot metal surfaces (NIOSH,
             1979a).  When heated to decomposition it emits toxic fumes of
             chlorine (Sax, 1984).
             Chloroform explodes when in contact with aluminium powder or
             magnesium powder.

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    The main use of chloroform is the production of
                    other materials,principally fluorocarbons (for
                    example, chlorodifluoromethane) used in the synthesis
                    of tetrafluoroethylene and polytetrafluoroethylene,
                    and as a refrigerant and propellant.  Chloroform is
                    also widely employed as an organic solvent in
                    industryand in analytical laboratories.  It has also
                    been used as an ingredient of pharmaceuticals, drugs,
                    cosmetics, grain fumigants, dyes and pesticides.
                    The United States Food and Drug Administration listed
                    some 1900 human drug products containing chloroform in
                    1976 (IARC, 1979) but its pharmaceutical use has been
                    restricted in many countries. Chloroform may be a drug
                    of abuse.

                    Worldwide production of chloroform in 1973 was about
                    2.5 million tonnes (Ross et al., 1978).

        4.2  High risk circumstance of poisoning

             Exposure may be occupational or by voluntary ingestion
             or inhalation for its psychotropic effects (Hutchens 1985;
             Storms,1973; Iffland & Ramme, 1983; Beer et al.,

        4.3  Occupationally exposed populations

             High risk circumstances of acute and chronic poisoning
             occur mostly in chemical plants where chloroform is
             manufactured and used and in chemical laboratories which use
             chloroform as a solvent.  Transport and storage of improperly
             closed containers also creates a high risk. Chronic exposure 
             may occur in farmers using pesticides containing chloroform
             (for instance, grain fumigants); in people dealing with drugs
             and cosmetics containing chloroform; and in users of such


        5.1  Oral

             Acute poisoning may be due to accidental or deliberate
             ingestion. Chloroform is readily absorbed through mucous
             membranes (Davidson et al., 1978). Although water, food and
             oral drugs contain minute amounts of chloroform, significant
             chronic poisoning is unlikely by this route.

        5.2  Inhalation

             Inhalation is the most frequent and the most important
             route of entry of chloroform. Poisoning by this route is also
             best understood from experience of its use as a general
             anaesthetic until it was replaced by less toxic
             Up to 64-67% of chloroform from inspired air is retained in
             the body. Pulmonary intake is directly related to the
             chloroform concentration in the air, the ventilation volume
             and to the duration of exposure (Davidson et al.,1978).

        5.3  Dermal

             Dermal exposure may cause irritation (especially of the
             most sensitive areas such as the anogenital region and,
             although absorption via this route is usually not
             significant, systemic effects changes may occur which
             resembling those produced by inhalation (Royal Society of
             Chemistry, 1986).

        5.4  Eye

             Liquid chloroform irritates the eye but systemic
             absorption is not significant.

        5.5  Parenteral

             Parenteral administration may be an act of deliberate
             self poisoning, criminal poisoning or medical error.

        5.6  Others

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             The gastrointestinal absorption of chloroform has not
             been satisfactorily studied but is said to occur readily; the
             peak blood concentration occurs one hour after ingestion
             (Davidson et al., 1978).
             Inhalation is the principal route of entry of chloroform into
             the body. The total quantity absorbed through the lungs is
             directly proportional to:
                the concentration in the inspired air;
                the exposure time;
                the blood/air Ostwald solubility coefficient;
                the solubility in the various body tissuesphysical
             The basic kinetic parameters of chloroform absorption by
             inhalation and its equilibration in the body apply equally to
             both low and high concentrations. At concentrations inducing
             anaesthesia (8000 - 10,000 ppm), a high blood level (about
             100 mg/l) is obtained within a couple of minutes.
             Skin exposure:  rarely causes absorption of significant
             amounts of chloroform.

             Ocular exposure:  small amounts may be absorbed.

        6.2  Distribution by route of exposure

             The distribution of chloroform in the body does not
             differ qualitatively between the various routes of exposure.
             Chloroform is rapidly absorbed and distributed to all body
             tissues (IARC, 1979).  Chloroform is lipophilic and therefore
             it concentrates mainly in lipid-containing organs such as
             adipose tissue, the central nervous system, kidney and liver.
             Chloroform remains in these tissues at least for several
             hours after exposure and accumulation of chloroform in the
             body will occur during repeated exposures.
             Chloroform passes the placental barrier and it has been found
             in fresh cow's milk; it probably occurs in human colostrum
             and mature milk (Davidson et al., 1978).

        6.3  Biological half-life by route of exposure

             No data available.

        6.4  Metabolism

             Chloroform is extensively metabolized by the liver.
             Phosgene, carbene and chlorine are some of the metabolites
             which may account for its cytotoxic activity.

        6.5  Elimination by route of exposure

             The elimination of chloroform is not qualitatively
             affected by the route of exposure.  About 60 - 70% is
             eliminated unchanged in expired air; 30 - 40% is metabolized
             and excreted in urine and faeces. Its metabolism is
             dose-dependent and may be proportionally higher at lower
             exposures (Davidson et al., 1979).


        7.1  Mode of Action

             Chloroform causes progressive depression of the central
             nervous system, ultimately producing deep coma and
             respiratory centre depression. It is also hepatotoxic and
             nephrotoxic, although liver and kidney damage can be
             influenced by various treatments which affect hepatic
             drug-metabolizing enzymes  (IARC, 1979): induction of hepatic
             enzymes with barbiturates, DDT or ethanol potentiates hepatic
             cell necrosis and kidney damage (NIOSH, 1979b). The reactive
             intermediates of chloroform metabolism (phosgene, carbene and

             Cl) which bind covalently and irreversibly to cellular
             macromolecules are believed to account for cellular damage
             within the liver and kidney (Davidson et al., 1978).

        7.2  Toxicity

             7.2.1  Human data


                             Chloroform has been widely used as
                             an anaesthetic but it has now been abandoned
                             due to its toxicity. Prolonged administration
                             as an anaesthetic may lead to profound
                             toxaemia and damage to the liver, heart and
                             kidneys. Inhalation of concentrated
                             chloroform vapour causes irritation of
                             exposed mucous surfaces.  Narcosis is
                             ordinarily preceded by a stage of excitation
                             which is followed by loss of
                             reflexes,sensation and


                             No specific data available.

             7.2.2  Relevant animal data

                    Concentrations of 68,000 - 28,000 ppm kill most
                    animals in a few minutes; 14,000ppm is dangerous to
                    life after an exposure of 30 to 60 minutes; 5,000 to
                    6,000 ppm can be tolerated by animals for one hour
                    without serious disturbances. The maximum
                    concentration tolerated for several hours or for
                    prolonged exposure with slight symptoms is 2,000 to
                    2,500 ppm. The harmful effects are narcosis, and
                    damage to the liver and heart. Experimentally
                    prolonged but light anaesthesia in dogs produces a
                    typical hepatitis.

             7.2.3  Relevant in vitro data

                    No recent references available providing
                    reliable relevant information.

             7.2.4  Workplace standards

                    NIOSH recommends a time-averaged limit of 10
                    ppm (NIOSH 1979b).

             7.2.5  Acceptable daily intake (ADI) and other guideline

                    Data not available.

        7.3  Carcinogenicity

             There is sufficient evidence that chloroform is
             carcinogenic in mice and rats. In the absence of adequate
             data in humans, it is reasonable for practical purposes to
             regard chloroform as potentially carcinogenic in man (IARC,
             1979).  Animal data should be extrapolated to man only with
             caution. Nonetheless, when theoretical risk assessment models
             are applied to the available data, the estimated virtual
             human dose for a cancer risk of 1 per million is 0.26 mg/day
             or less. In animals, very low levels of chloroform (0.75 and
             75 ppm) in the drinking water (equivalent to about 0.15 and
             15 mg/kg/day in mice) appears to be sufficient to promote the
             growth and spread of tumours (Davidson et al., 1978).

        7.4  Teratogenicity

             Chloroform is teratogenic in the rat, mouse and rabbit
             (IARC, 1979) but human data are not available.

        7.5  Mutagenicity

             Chloroform is not mutagenic in animals; no human data
             are available (IARC, 1979).

        7.6  Interactions

             Chloroform is more hepatotoxic and nephrotoxic when
             administered after alcohols, barbiturates or DDT (NIOSH,


        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

            Toxicological analyses

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

            Toxicological analyses

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

            Toxicological analyses

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

        8.2  Toxicological Analyses and their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

            Simple Qualitative Test(s)

            Advanced Qualitative Confirmation Test(s)

            Simple Quantitative Method(s)

            Advanced Quantitative Method(s)

             8.2.2  Tests for biological specimens

            Simple Qualitative Test(s)

            Advanced Qualitative Confirmation Test(s)

            Simple Quantitative Method(s)

            Advanced Quantitative Method(s)

            Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

            Blood, plasma or serum


            Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and
             their interpretation

        8.5  Overall Interpretation of all toxicological analyses and
             toxicological investigations

             Collect samples of blood and urine for biomedical
             analyses mentioned below.
             Estimation of chloroform or its metabolites in the body
             fluids plays no practical role in the management of acute or
             chronic poisoning.
             Arterial O2, CO2 and pH should be monitored in cases of
             severe poisoning with respiratory failure. 
             Monitor serum bilirubin, transaminases, plasma prothrombin
             alkaline phosphatase and gamma-glutamyl transpeptidase to
             detect the degree of liver damage. In case of liver damage
             increased urinary concentrations of bilirubin may occur.
             Daily urine collection, plasma creatinine and urea
             measurement are needed to detect renal failure.
             Chloroform is toxic to the bone marrow and may also cause a
             deficiency of plasma prothrombin and fibrinogen. A full blood
             count should be performed; monitor plamsa prothrombin and
             fibrinogen (Winslow & Gerstner, 1978).
             In severe cases, serum electrolytes, urea and creatinine
             should be monitored. Glucose may be elevated and ketoacidosis
             found due to the incomplete oxidation of fats (Winslow &
             Gerstner, 1978).

             Estimation of chloroform or its metabolites in the body
             fluids plays no practical role in the management of acute or
             chronic poisoning.
             Chloroform may be measured in the air of the workshop
             atmospheres using portable or static sampling devices 
             (NIOSH, 1979a), in water and food (Kaiser & Oliver, 1976;
             Piet et al., 1978; Simmonds & Kerns, 1979; Gruber, 1984;
             Ploder, 1974; Pereira & Hughes, 1980) and in the biological
             fluids (blood, urine) or tissues of the poisoned person
             (Peoples et al., 1979).
             The following spectroscopic data are available  (Grasselli &
             Ritchley, 1975): infra-red, Raman, ultraviolet, nuclear
             magnetic resonance and mass spectrometry. The concentration
             of chloroform in air is measured, as recommended by NIOSH
             (1977), by an activated charcoal trapping method for
             collection and concentration, followed by solvent extraction
             of the charcoal and a gas chromatographic (GC) analysis of
             the extract. 
             The collection tube is 7 cm long with a 4 mm internal
             diameter. It contains a total of 150 g of activated charcoal
             (20-40 mesh), divided into a front section of 100mg and a
             rear section of 50mg separated by a plug of urethane foam. 
             Air is sampled at a flow rate of 200 ml per minute by means
             of a small pump.  The entire apparatus is portable and it may
             be carried in a pocket with the sampling tube in the
             breathing zone (normally a coat lapel).  The apparatus can
             also be static.
             Carbon disulphide is used to extract the chloroform, which is
             separated on a 6.10 m by 3.18 mm stainless steel packed with
             10% FFAP on Chromosorb using flame ionization detection.
             Water samples are purged with helium and the volatile
             substances including chloroform are trapped on Tenax-GC prior
             to GC analysis. A Tracor conductivity detector, operated in
             the catalytic pyrolysis mode, was used successfully in place
             of the usual electron capture detection (Pape, 1977).
             Blood, serum and various adipose tissues were extracted with
             hexane the extract was heated at 115 C and the volatiles
             collected in a Tenac-silica gel trap (Peoples et al., 1979). 
             Chloroform, together with carbon tetrachloride,
             1,2-dichloroethane and trichloroethylene were thermally
             adsorbed and determined by GC on a 1.83 m by 6.35 mm column
             packed with Porasil C supporting octane.  Temperature
             programming and a halide-specific detector were used.

        8.6  References


        9.1  Acute poisoning

             9.1.1  Ingestion

                    Clinical effects of acute poisoning are due to
                    effects on both the central (headache, various degrees
                    of impaired consciousness, convulsions, respiratory
                    centre paralysis) and the autonomic nervous systems
                    (dizziness, nausea, vomiting). These symptoms occur
                    immediately after toxic exposure. Later, symptoms of
                    liver and kidney may develop. The main features of
                    acute poisoning do not depend on the route of entry
                    but rather on the amount of chloroform absorbed by the
                    Direct irritation of the gastrointestinal tract causes
                    abdominal pain, nausea, vomiting, diarrhoea; later
                    involvement of the autonomic nervous system also
                    causes nausea and vomiting.

             9.1.2  Inhalation

                    Inhalation is the most frequent and most
                    important route of poisoning with chloroform.  Mild
                    poisoning causes slight shortness of breath and
                    dizziness. More severe poisoning causes nausea,
                    vomiting, drowsiness and various levels of impaired
                    consciousness, convulsions and respiratory centre
                    Later, symptoms of liver and kidney may develop. The
                    main features of acute poisoning do not depend on the
                    route of entry  but rather on the amount of chloroform
                    absorbed by the body.

             9.1.3  Skin exposure

                    Irritation and redness may occur at the site of
                    contact, especially of the more sensitive skin parts
                    (eyelids, neck, axillae,  anogenital region) and burns
                    may occur. Chloroform may be absorbed through the skin
                    and cause systemic symptoms, although this route of
                    absorption is not normally significant.

             9.1.4  Eye contact

                    Eye contact with liquid chloroform results in
                    painful irritation of the superficial eye structures,
                    burns and may cause corneal necrosis and

             9.1.5  Parenteral exposure

                    Parenteral exposure is unlikely except as a
                    result of a voluntary poisoning or medical error.  The
                    systemic effects appear very rapidly (see

             9.1.6  Other

                    No data available

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    A man who ingested cough mixture containing 1.6
                    to 2.6 g of chloroform daily for 10 years developed
                    hepatitis and nephrosis. Severe cellular changes were
                    found on liver biopsy in another man who had ingested
                    21 ml of chloroform daily for an undetermined period.
                    No evidence of harm could be found in users of a
                    dentifrice containing 3.4% chloroform and a mouthwash
                    containing 0.43% (Pohl, 1979).
                    Surprisingly few clinical data are available
                    concerning chronic human exposure to chloroform
                    despite its long history of use and there are almost
                    no quantitative toxicological studies (Clayton and
                    Clayton, 1981; IARC, 1979).

             9.2.2  Inhalation

                    Habitual inhalation of 1 oz of chloroform daily
                    for 7 years followed by 2 oz daily for a further 5
                    years was associated with delusions, restlessness,
                    depression, convulsions, ataxia, dysarthria, tremor of
                    the tongue and fingers, and insomnia (NIOSH,

             9.2.3  Skin exposure

                    No data available.

             9.2.4  Eye contact

                    No data available.

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             Acute poisoning with chloroform may follow a benign
             course and leave no permanent damage. However, after rapid
             absorption of high doses, death occurs quickly due to
             respiratory paralysis or cardiac arrest, especially when
             proper cardio-respiratory resuscitation is not available.  If
             the patient survives this early dramatic phase, or when the
             exposure is less severe, moderate CNS depression is the most
             prominent effect of acute poisoning. The patient may be
             dizzy, stuporous or deeply unconscious and, if there is no
             further absorption, recovery occurs gradually 20-60 minutes
             after exposure, often with profuse vomiting.
             Lower doses result in dizziness, salivation, a feeling of
             pressure within the head, nausea and vomiting.
             After larger or repeated exposures, liver and, less
             frequently,overt kidney damage may develop after several
             days.  This may be followed by complete recovery within
             several weeks but may also have a fatal outcome, sometimes
             even within less than a week (Winslow & Gerstner,

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Early death after heavy exposure to chloroform
                    may be due to ventricular fibrillation by a direct
                    effect of chloroform on the myocardium, through vagal
                    stimulation or by  sensitizing the heart to endogenous
                    or exogenous catecholamines (ILO, 1983).  Chloroform
                    also causes hypotension by decreasing the contractile
                    power of myocardium and peripheral vasodilatation
                    arising from vagal stimulation.

             9.4.2  Respiratory

                    Respiratory failure is due to paralysis of the
                    medullary respiratory centre, not a direct action of
                    chloroform on the respiratory system or to the
                    aspiration of vomitus. 

             9.4.3  Neurological

            Central Nervous System (CNS)

                             Depression of the CNS and even coma
                             are the most prominent effects of acute
                             Convulsions may occur. Paralysis of the
                             respiratory centre may cause sudden death.
                             Chronic exposure may cause restlessness,
                             depression, convulsions, ataxia, dysarthria,
                             tremor of the tongue and fingers and insomnia 
                             (NIOSH, 1979b).

            Peripheral nervous system

                             No data available

            Autonomic nervous system

                             Vagal stimulation is associated with
                             dilatation of pupils, nausea, vomiting,
                             salivation and profuse sweating (Clayton &
                             Clayton, 1981).  Vagal stimulation of the
                             heart causes various cardiac and peripheral
                             circulatory disturbances(see 9.1).

            Skeletal and smooth muscle

                             Relaxation of vascular smooth muscle
                             leads to hypotension (ILO, 1983).

             9.4.4  Gastrointestinal

                    Ingested chloroform irritates the
                    gastrointestinal mucosa and may even cause burns.  It
                    induces vomiting mostly through vagal stimulation but
                    also by a direct local action. Diarrhoea may also
                    occur (Winslow & Gerstner, 1978).

             9.4.5  Hepatic

                    The hepatotoxicity of chloroform is probably
                    due to the metabolites phosgene, carbene and chlorine
                    produced by the liver. Necrosis of liver cells may
                    occur (Winslow & Gerstner, 1978), causing increased
                    concentrations of serum bilirubin and transaminases. 
                    Deficiency of prothrombin and fibrinogen may also
                    occur (Winslow & Gerstner, 1978).  Chronic exposure
                    may cause liver damage although convincing evidence to
                    support this is lacking (Pohl, 1979).

             9.4.6  Urinary


                             Kidney damage is less common than
                             injury to the liver but it may occur after
                             acute exposure (Clayton & Clayton, 1981).
                             Acute exposure may be associated with damage
                             to the renal tubules, mainly involving the
                             epithelium of Henle's loop  (Winslow &
                             Gerstner, 1978). The renal effect may be due
                             to prolonged anoxia rather than to a direct
                             toxic effect on the kidney since proper
                             oxygenation seems to prevent renal damage 
                             (Waters, 1951).


                             No data available.

             9.4.7  Endocrine and reproductive systems

                    No data available.

             9.4.8  Dermatological

                    Local irritation and burns have been observed,
                    especially at the more sensitive skin areas.

             9.4.9  Eye, ears, nose, throat: local effects

                    Conjunctivitis and corneal injury occur after
                    eye contact. Oral mucosa may also be irritated.

             9.4.10 Haematological

                    Chloroform may damage the erythrocyte membrane
                    (NIOSH, 1979b); blood clotting may be impaired by
                    deficiency of prothrombin and fibrinogen (Winslow &
                    Gerstner, 1978).

             9.4.11 Immunological

                    No data available.

             9.4.12 Metabolic

           Acid-base disturbances

                             Ketoacidosis may occur (Winslow &
                             Gerstner, 1978).

           Fluid and electrolyte disturbances

                             Secondary to losses occur due to
                             vomiting and diarrhoea.


                             Hyperglycaemia may occur in acute
                             chloroform poisoning (Winslow & Gerstner,

             9.4.13 Allergic reactions

                    No data available.

             9.4.14 Other clinical effects

                    No data available.

             9.4.15 Special risks

                    Pregnancy:  No data available.
                    Breast feeding:  Chloroform probably occurs in human
                    colostrum and milk.
                    Enzyme deficiencies:  No data available.

        9.5  Others

             No data available.

        9.6  Summary


        10.1 General principles

             Paralysis of the respiratory centre or cardiac arrest
             (due to ventricular fibrillation) may cause instant death if
             the proper resuscitation measures are not started
             immediately.  The unconscious patient needs supportive
             treatment (under respiratory and cardiac monitoring) and
             possibly fluid replacement. Within a few days, hepatic and
             renal failure may develop. Forced diuresis, peritoneal or
             extracorporeal haemodialysis, haemoperfusion and
             plasmapheresis are useless in the management of acute
             chloroform poisoning but renal dialysis is essential if
             kidney failuredevelops.

        10.2 Life supportive procedures and symptomatic treatment

             Monitor respiratory and cardiac function. Respiratory
             assistance is often necessary and cardiac defibrillation may
             be needed.
             Haemodynamic status should be monitored and balanced using
             intravenous administration of fluids and electrolytes.

        10.3 Decontamination

             Emptying the stomach after ingestion is of questionable
             value because the absorption of chloroform is very rapid.
             Milk, fat or fatty emulsions should not be given orally or by
             gastric tube because they may enhance absorption. Clothing
             soaked with chloroform should be removed. After eye contact,
             wash with copious amounts of water; wash contaminated skin
             with soap and water.
             In case of spillage, instruct others to keep at a safe
             distance.  Wear breathing apparatus and gloves.  Apply a
             dispersing agent if available and work to an emulsion with a
             brush and wash into a waste system, diluting the chloroform
             greatly with copious running water.  If a dispersant is not
             available, absorb the spillage with sand and shovel it into a
             bucket; transport this to a safe, open area so that it can
             evaporate into the air. The site of the spillage should be
             washed thoroughly with water and soap or detergent 
             (Bretherick, 1981).

        10.4 Enhanced elimination

             No data available

        10.5 Antidote treatment

             10.5.1 Adults

                    Not known

             10.5.2 Children

                    Not known

        10.6 Management discussion

             No data available


        11.1 Case reports from literature

             A 19-year old man who was at a "chloroform party"
             consumed three bottles of beer and then mistakenly drank an
             unknown quantity of chloroform. He collapsed and was taken to
             a local emergency room, where he was found to be stuporous.
             His blood pressure was 110/60 mmHg.  He was immediately
             transferred to the medical intensive care unit at the
             University of Wisconsin Hospital.  By that time he was
             comatose, cyanosis was present, and his breathing was
             laboured.  His blood pressure was 100/40 mmHg; pulse rate 108
             beats per minute; and respiration 26/min.  The only other
             relevant physical finding was hypoactive deep tendon
             Because of poor ventilatory effort, the patient was intubated
             and breathing was controlled on a volume ventilator. Hypoxia
             could be corrected only with continuous positive pressure
             ventilation.  The initial haematocrit value, white blood cell
             count, urinalysis, all levels of blood urea nitrogen,
             electrolytes, fibrinogen, and blood glucose were normal. 
             Euglobulin lysis took more than 24 hours.  Liver function
             abnormalities during hospitalization and on follow-up
             examination are shown in the table.

             Days Following Ingestion
                                 1     2     3       4       6      90
             SGOT (IU)           30    681   8080    5300    297    34
             SGPT (IU)           15    -     9220    10250   3330
             LDH  (IU)           204   636   9280    5680    630    176
             (mg/dl)             0.2   2.3    2.4     2.7    1.3    1.0
             (IU)                6.1   5.2      -     6.4    -      5.0
             time (sec):
             Patient             14.3  19.3     -     18.4   14.3   12.3
             Control             12.6  11.9     -     12.7   11.8   12.2

             Ten hours after ingestion, the chloroform level in blood was
             200 mg/l. Three days after admission, the patient began to
             respond and was extubated. Cerebellar damage was noted,
             characterized by instability of gait and a slight tremor on
             finger-to-nose testing.  These findings returned to normal in
             two weeks.  Liver function tests eight weeks after discharge
             were normal (Storms 1973).


        12.1 Specific preventive measures

             The work place atmosphere should not contain more than
             10 ppm of chloroform.
             Shipping and storage containers should carry a label warning
             that chloroform is highly dangerous because of its toxic and
             carcinogenic properties (ILO, 1983).  Containers of
             chloroform should be kept closed when not in use. Activities
             in which chloroform is used should be isolated and work
             should be performed with adequate ventilation.  Workers
             should be trained to handle the material safely.  Protective
             clothing, gloves, eye protection, shields and respirators
             should be provided.  Recommendations for work practices,
             labelling, personal protective equipment,  protective
             clothing and sanitation are included in the references
             (NIOSH, 1979a, 1979b) 

        12.2 Other

             No data available.


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        National La., July 1978
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        ECSC-EEC-EAEC, Brussels-Luxembourg
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        ADDRESS (ES)

        Authors:    Janusz Szajewski, M.D. 
                    Szpital Praski
                    Dept.3 of Medicine & Warsaw Poison Control Centre 
                    03-701 Warsaw 
                    Tel:(4822) 19 08 97/19 66 54, 
                    Fax:(4822) 26 38 33

        Date:       August 1990
        Review:     Newcastle-upon-Tyne, United Kingdom, January 1991

        Update:     Dr R. Fernando, June 1993

    See Also:
       Toxicological Abbreviations
       Chloroform (EHC 163, 1994)
       Chloroform (HSG 87, 1994)
       Chloroform (ICSC)
       Chloroform (WHO Food Additives Series 14)
       CHLOROFORM (JECFA Evaluation)
       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)