Carbon disulfide

   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 circumstances 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 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 102

    1.  NAME

        1.1  Substance

             Carbon disulfide

        1.2  Group

             Inorganic carbon compound

        1.3  Synonyms

             Carbon bisulfidey,
             Carbon sulfide,
             Dithiocarbonic anhydride,
             solfuro di carbonio,
             sulfure de carbone,
             sulphocarbonic anhydride,

        1.4  Identification numbers

             1.4.1  CAS number


             1.4.2  Other numbers

                    EPA Pesticide chemical code: 016401
                    NIOSH: FF6650000
                    UN Hazard class: 3 (flammable liquids)
                    UN Pack Group: I
                    UN subsidiary risks: 6.1 (poisonous substance)
                    UN: 1131

        1.5  Main brand names, main trade names

             Weeviltox, NCI-CO4591

        1.6  Main manufacturers, main importers

             It is widely produced by many chemical companies.

    2.  SUMMARY

        2.1  Main risks and target organs

             Acute toxic effects include central nervous system
             depression, peripheral neuropathy and cardiovascular
             collapse.  Dyspnoea and respiratory failure may occur
             following exposure to high concentration.  Carbon disulphide
             is irritant to eyes and skin and may cause corneal erosions
             and chemical burns respectively.  Chronic exposure may cause
             neuropsychiatric disorders, peripheral neuropathies and
             increased risk of atheroma.

        2.2  Summary of clinical effects

             Acute carbon disulphide poisoning is rare but very
             dangerous. Absorption occurs through the skin, by ingestion
             or by inhalation. In severe poisoning, the patient rapidly
             becomes comatose and death occurs in a few hours, usually due
             to respiratory depression and convulsions.
             In less severe cases local irritation, nausea, vomiting and
             abdominal pain are followed by headache, euphoria,
             hallucinations, manic delirium, paranoid reactions and
             suicidal tendencies.
             Chronic occupational exposure is more common.  After 10 -15
             years it may cause sensory and motor neuropathy,
             neuropsychiatric changes and parkinsonism.  Atherosclerosis,
             in particular coronary heart disease, impaired vision 
             (perception of coloured rings around lights and retinal
             changes), renal and hepatic damage, and permanent impairment
             of reproductive function also occur after long-term
             exposures.  In addition, sleep disturbance, fatigue, anorexia
             and weight loss are common complaints among exposed workers.
             Local contact may result in irritation, burning sensation,
             blistering or deep burns.  Conjunctivitis, pain and blurred
             vision result from exposure of the eyes to the vapour, and
             severe irritation or burns occur after direct contact.

        2.3  Diagnosis

             The diagnosis is made on the history of exposure and the
             presence of clinical effects. In acute poisoning by
             ingestion, there may be nausea, vomiting and abdominal pain
             followed by headache, euphoria, hallucinations, manic
             delirium, dyspnoea, cyanosis, peripheral vascular collapse,
             convulsions and coma.

             Carbon disulphide can be measured in blood, urine and breath
             but this is not useful in the management of poisoning.
             Dithiocarbamine (DTS) may also be measured in urine.
             In chronic occupational exposure, the diagnosis is made from
             the presence of sensory and motor neuropathy,
             neuropsychiatric changes, parkinsonism, renal and hepatic
             damage, sleep disturbance, fatigue, anorexia and weight

        2.4  First-aid measures and management principles

             Remove patient to fresh air if carbon disulphide is
             inhaled. In cases of ingestion do not induce vomiting.
             Perform gastric aspiration or lavage if the toxin was
             recently ingested. Wash contaminated skin with soap and
             water. Irrigate contaminated eyes copiously with water.
             In case of severe poisoning, support respiration, administer
             oxygen and monitor cardiovascular function.
             There is no specific antidote. Give symptomatic and
             supportive treatment as required.


        3.1  Origin of the substance

             Carbon disulfide was formerly manufactured by direct
             reaction of sulphur vapour and coke in iron or steel retorts
             at 750 - 1000°C but, since the early 1950's, the preferred
             method of synthesis has been the catalyzed reaction between
             sulphur and methane:
             CH4 + S              CS2 + 2H2S
             SiO2.gel  or
             (Greenwood & Earnshaw, 1984)
             Carbon disulfide is a natural product of anaerobic
             biodgradation. In nature, minute amounts occur in coal tar
             and in crude petroleum (Merck, 1979). Other sources include
             animal waste, in particular pig urine and faeces, fish
             processing, plastic and refuse combustion, synthetic fibre
             and starch manufacture, turbines, natural gas and

        3.2  Chemical structure

             CS2                       S = C = S
             Molecular weight:  76.14

        3.3  Physical properties

             3.3.1  Colour


             3.3.2  State/form


             3.3.3  Description

                    Pure carbon disulfide is a clear colourless,
                    highly refractive, mobile, volatile, very flammable
                    liquid.  The pure liquid has a rather pleasant
                    ethereal odour, while the usual commercial and reagent
                    grades are yellowish and foul smelling (decaying
                    radishes).  Decomposes on prolonged standing.
                    Boiling point:     46.5°C at atmospheric pressure
                                       (760 mmHg)
                    Melting point:     -111.6°C
                    Flash point:       -30°C (closed cup)
                    Explosive limits:  lower 1.0%, upper 50.0% vol/vol
                                       in air.
                    Auto ignition
                    point:             100°C
                    Carbon disulfide is spontaneously flammable at
                    Can be ignited by hot steam pipes (Merck)
                    It burns with a blue flame to carbon dioxide and
                    sulphur dioxide.
                    Density (liquid):  1.2632 at 20°C
                    Vapour density:    2.67 (air = 1)
                    Solubility in water at 20°C:  0.294 g/100 ml
                    Solubility of water in carbon disulfide: 0.005%
                    Miscible with anhydrous methanol, ethanol, ether,
                    benzene, chloroform, carbon tetrachloride, oils.
                    Azeotrope with water, boiling point 42.6°C, contains
                    97.2% carbon disulfide
                    Can be stored in iron, aluminium, glass, porcelain,
                    Teflon  (Merck, 1989).
                    Fats and lipids are soluble in carbon disulfide and it
                    is also a solvent for waxes, lacquers, camphor, resins
                    and vulcanized rubber.

                    Carbon disulfide undergoes slow decomposition in

        3.4  Hazardous characteristics

             The vapour is denser than air and therefore sinks to the
             ground.  Carbon disulfide dissolves phosphorous, sulphur,
             selenium, bromine, iodine, fats, resins and rubber (Merck)
             (check limit in detection and development on

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    The principal industrial uses of carbon
                    disulfide are the manufacture of viscose rayon,
                    cellophane film, carbon tetrachloride and
                    xanthogenates and electronic vacuum tube (Greenwood &
                    Earnshaw, 1984 & Merck Index 1989).
                    Carbon disulfide is also used as an insecticide for
                    the fumigation of grains, nursery stock, in fresh
                    fruit conservation and as a soil disinfectant against
                    insects and nematodes (British Crop Protection
                    Council, 1987).Carbon disulfide is a solvent for
                    phosphorous, sulfur, selenium, bromine, iodine, fats,
                    resins, rubber (Merck, 1987).
                    Used for fumigation in airtight storage warehouses,
                    airtight flat storages, bins, grain elevators,
                    railroad box cars, shipholds, barges and cereal

        4.2  High risk circumstances of poisoning

             Accidental ingestion or inhalation of carbon disulfide
             occurs usually in an industrial setting.

        4.3  Occupationally exposed populations

             Carbon disulfide is typically an industrial chemical and
             exposure is almost exclusively confined to occupational
             situations.  In theory, any worker engaged in processes using
             carbon disulfide may be exposed to some degree.  However, in
             practice, only workers in the viscose rayon industry are
             exposed to concentrations high enough to have deleterious
             effects on health.

             For every kilogram of viscose used, about 20 - 30 g of carbon
             disulfide and 4 - 6 g of hydrogen sulfide will be emitted. 
             About 0.6 - 1.0 kg of viscose is used per hour in the
             different processes involved in the production of textile
             yarn.  However, exposure to carbon disulfide is usually
             highest in connection with the production of staple fibre and
             cellophane, where the equivalent amounts of viscose used are
             approximately 70 - 100 kg and 1,800 - 2,000 kilograms per
             hour respectively (WHO, 1979).
             Some cases of acute exposure have occurred during the process
             of tank cleaning, in spills and fires involving the product
             (WHO, 1979).


        5.1  Oral

             Poisoning by ingestion is uncommon.

        5.2  Inhalation

             Inhalation is the commonest route of absorption of
             carbon disulphide in man.

        5.3  Dermal

             Skin contact is a significant route of absorption,
             although much less important than inhalation.

        5.4  Eye

             No data available.

        5.5  Parenteral

             No data available.

        5.6  Others

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             Inhalation represents the main route of absorption; in
             man, an equilibrium between the carbon disulphide
             concentration in inhaled and exhaled air is reached during
             the first 60 minutes of exposure.  The percentage retained at
             equilibrium appears to be about 40 - 50% of the amount of
             carbon disulphide in the inhaled air and depends on both the
             concentration of carbon disulphide in the air and the
             partition coefficient between blood and tissues.  This
             percentage is lower in continuously exposed workers than in
             volunteers exposed for the first time to carbon disulphide
             (WHO, 1979).
             Concentrations of 1 - 1.2 mg/L (320 - 390 ppm) are bearable
             for several hours, but headaches and unpleasant feeling
             appear after 8 hours.  At 3.6 mg/L (1,150 ppm) giddiness sets
             in, and mild intoxication occurs after exposure for 30 min - 
             1 hour to 6.4 - 10 mg/L (2,000 - 3,200 ppm).  At
             concentrations over 15 mg/L (4,800 ppm) unconsciousness
             occurs after several inhalations (ILO, 1983).
             Carbon disulphide can be absorbed through the skin and this
             has been confirmed in a number of studies.  The rate of
             absorption is proportional to its the concentration. It was
             estimated that immersion of one hand for one hour in a
             washing bath solution containing 0.1 mg/L carbon disulphide
             at a viscose rayon plant resulted in the absorption  of 17.5
             mg of carbon disulphide (CEC, 1988).
             Ingestion is rare, but may cause serious toxicity.

        6.2  Distribution by route of exposure

             Carbon disulphide is distributed in the blood stream;
             and the erythrocyte:plasma ratio is 2:1. It is rapidly
             cleared from the blood compartment and because of this the
             determination of carbon disulphide in blood is not a useful
             test in exposure.
             Carbon disulphide can exist in both "free" and 'bound' forms
             to plasma proteins, the bound form is the fraction that has
             reacted with amino acids to give thiocarbamates (in a
             reversible reaction).  "Free" carbon disulphide is rapidly
             eliminated and is usually undetectable.
             These two forms of carbon disulphide and different tissue
             affinities may explain the conflicting clinical reports (WHO,

        6.3  Biological half-life by route of exposure

             Carbon disulphide disappears very rapidly from the
             blood. The partition coefficient is 2.8 (air:blood). The
             plasma elimination half-life is about 1 hour (WHO,

        6.4  Metabolism

             Around 70 - 90% of the retained carbon disulphide is
             metabolized and excreted in the urine.  Carbon disulphide
             undergoes microsomal hepatic metabolism, with subsequent
             conjugation.  Some of the metabolites detected in the urine
             are thiourea (the most important) and mercaptothiazoline and
             2-mercapto-thiazoline-4-carbonic acid, but there appears to
             be a poor correlation between the amount of metabolites and
             the degree of exposure.

        6.5  Elimination by route of exposure

             Exhalation is the primary route of excretion of
             unmetabolized carbon disulphide; 10 - 30% of the amount
             absorbed is exhaled. Less than 1% is excreted unchanged in
             the urine and 70 - 90% undergoes metabolism and excretion
             (CEC, 1988). Respiratory elimination takes place in 3 phases: 
             a first phase of rapid elimination of the carbon disulphide
             absorbed on the mucosa of the lungs and upper respiratory
             tract;  secondly, a slower phase, with exhalation of carbon
             disulphide released from the blood, and thirdly, a very slow
             phase, where carbon disulphide released from tissues and
             organs is exhaled. Animal studies show that carbon disulphide
             undergoes desulphuration and the released carbon is exhaled
             as carbon dioxide.
             Small quantities of carbon disulphide are excreted in saliva,
             sweat and through the skin of exposed workers. Elimination of
             carbon disulphide in faeces is negligible (WHO, 1979).


        7.1  Mode of Action

             Carbon disulphide reacts with a variety of nucleophilic
             compounds in the body, characterized by the presence of a
             functional group with a free pair of electrons in the
             molecule  (mercapto-, amino-, hydroxyl-).  The majority of
             biochemically important compounds (e.g. pyridoxamine,
             cerebral monoamine oxidases, dopamine carboxylases, amino
             acids, biogenic amines and sugars) contain nucleophilic
             groups and may react with carbon disulphide.  Thus, a number
             of possible mechanisms for the effects of carbon disulphide
             have been postulated:

             -  acute CNS toxicity and peripheral neurotoxicity may be
                attributed to the formation of dithiocarbamates (CEC,
             -  non-enzymatic reaction of carbon disulphide with free
                amino groups indicates possible reaction with
                macromolecules such as enzymes, structural proteins,
                polypeptides and nucleic acids (CEC, 1988).
             -  the chelating effect of carbon disulphide metabolites 
                (dithiocarbamates) on various essential metals,
                required for the functioning of enzymes (e.g. zinc and
                copper); the neurotoxic action of carbon disulphide
                could easily be explained by chelating effects on both
                metals (WHO, 1979).
             -  an effect of carbon disulphide on enzymatic systems: 
                acute oral chronic exposures of animals to carbon
                disulphide result in changes of mitochondrial
                respiration and oxidative phosphorylation (WHO,
             -  disturbance of vitamin metabolism:  carbon disulphide
                alters the metabolism of vitamin B6 and nicotinic acid
                (WHO, 1979).
             -  impairment of catecholamine metabolism:  there is a
                decrease in the level of noradrenaline and increase in
                the level of dopamine.  Brain dopamine B-hydroxylase
                is inhibited and unable to convert dopamine into
                noradrenaline.  The inhibition of the enzyme occurs
                through the conversion of carbon disulphide to
                diethylthiocarbonate which chelates the cupricions
                essential for the enzyme function (CEC, 1988).
             -  disturbances in lipid metabolism, which lead to
                elevated total and esterified cholesterol levels in
                serum.  Changes in the lipid metabolism may lead to
                development of atheromatous changes in the aorta (WHO,
             -  interaction with microsomal drug metabolism:  an
                important feature of the liver toxicity caused by
                carbon disulphide seems to be the deactivation of
                cytochrome P450.  This effect is due to the oxidative
                desulfuration of carbon disulphide by mixed-function
                oxidases (De Matteis & Seawright, 1973).  The
                resulting highly reactive sulphur becomes covalently
                bound to the microsomal protein, mainly to the

                apoprotein of cytochrome P450.  It is possible that
                the liberated sulphur is the real toxic agent in liver
                toxicity arising from carbon disulphide exposure (WHO,

        7.2  Toxicity

             7.2.1  Human data


                             Lethal doses by ingestion are 30-60
                             ml, but an early report suggests that 15 ml
                             may be fatal in an adult (Davidson & Feinleb,
                             1972).  Mild intoxication, paraesthesia and
                             irregular breathing occur within 30-60
                             minutes exposure to 6.4 to 10 mg/l
                             (2,000-3,200 ppm). A concentration of 15 mg/l
                             (4,800 ppm) has proven lethal after 30
                             minutes, and at higher concentrations,
                             unconsciousness occurs after several
                             inhalations (ILO, 1983).
                             Prolonged exposures to vapour concentrations
                             at lower concentrations resulted in
                             significant health effects (CEC, 1988).
                             Women appear to be more sensitive than men to
                             the neurotoxic effect of carbon disulphide 
                             (Gosselin et al., 1984).


                             No data available.

             7.2.2  Relevant animal data

                    Numerous studies of the toxicokinetics and
                    metabolism of carbon disulphide, have been carried out
                    in rats, mice, rabbits, cats and dogs.  Rats are the
                    most resistant and dogs the most sensitive species to
                    neurotoxicity.  In acute exposure studies,
                    neurological signs prevail and many biochemical
                    changes have been demonstrated, such as inhibition of
                    microsomal mixed-system oxidases, destruction of
                    cytochrome p 450 in the liver, disturbances of
                    catecholamine metabolism and enzymatic changes (WHO,
                    1981).  With phenobarbital pre-treated rats, the
                    decline of cytochrome p 450 is greater and
                    centrilobular hydropic degeneration occurs in the

                    Data provided by RTECS (1986) are:
                    oral LD50 - rat          3,188 mg/kg
                    oral LD50 - mouse        2,780 mg/kg
                    oral LD50 - rabbit       2,550 mg/kg
                    oral LD50 - guinea pig   2,125 mg/kg
                    Most of the experimental studies have shown that
                    carbon disulphide can directly affect the CNS and
                    peripheral nervous system, resulting in axonal damage
                    (CEC, 1988).

             7.2.3  Relevant in vitro data

                    Available from RTECS

             7.2.4  Workplace standards

                    Minimum Alveolar Concentration (MAC):  20ppm
                    expressed in parts of air.  The threshold limit value
                    (TLV) in Britain was reduced to 10 ppm in 1980 whereas
                    the U.S. National Institute of Occupational Safety and
                    Health recommends a level of 1 ppm.MAC level
                    recommended by group of WHO experts:  60 mg/m3 (no
                    more than 15 minutes).  MAC (men workers)  10 mg/m3
                    MAC (women workers)  3 mg/m3 (ppm)

             7.2.5  Acceptable daily intake (ADI) and other guideline

                    No data available.

        7.3  Carcinogenicity

             Both animal and human data are inconclusive.  Carbon
             disulphide has been associated with bone marrow hyperplasia,
             lymphatic leukaemia and lymphosarcoma but the data available
             are very limited (CEC, 1988).

        7.4  Teratogenicity

             There is a weak teratogenic effect in the rat following
             low-level exposure to a combination of hydrogen sulphide and
             carbon disulphide.  There was evidence of embryotoxicity in
             the cat.  Embryonic alterations were induced in cats exposed
             to carbon disulphide during gestation (WHO, 1979).

        7.5  Mutagenicity

             Studies on Salmonella typhimurium, Drosophila, human
             fibroblasts, cultures of human blood leucocytes and rats have
             been inconclusive and further investigation is needed (CEC,

        7.6  Interactions

             Repeated exposure to a concentration of carbon
             disulphide of 3,900 units for 2 hours per day over a period
             of 20 - 30 days prolonged both the hexobarbital sleeping time
             and alcohol retention time in rats and mice (Lazarev et al.,
             1965).  Carbon disulphide caused reversible inhibition of the
             oxidative drug metabolism in human liver endoplasmic
             reticulum.  The treatment led to a rapidly reversible but
             significant decrease in the oxidative N-demethylation of the
             There seems to be synergy between alcohol and carbon
             disulphide.  The age factor and simultaneous exposure to
             hydrogen sulphide may also be synergistic (CEC, 1988).


        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

        8.5  Overall Interpretation of all toxicological analyses and
             toxicological investigations

             Relevant laboratory analyses and other
             Sample collection
             Collect blood and urine for biomedical and toxicological
             Biomedical analysis
             Depending on the clinical condition of the patient
             appropriate investigations may include: blood gases, full
             blood count, electrolytes and urea, and liver function
             In chronic exposure the following may be required:
             cholesterol, glucose tolerance and thyroid function
             Toxicological analysis
             Urine and breath levels of carbon disulphide may be
             evaluated.  Because of the poor correlation with carbon
             disulphide concentrations in air as well as for analytical
             reasons, the concentration of carbon disulphide in blood is
             not a useful test of exposure. Dosage of mercaptothiozolinone
             in urine may be useful.
             Other investigations that may be appropriate include:
                    Blood pressure measurement
                    Full clinical neurological investigation
                    Electroneuromyographic studies and nerve conduction
                    studies (for early detection of peripheral
                    Optic fundus study and photography
                    Dexterity tests, simple reaction time, Wechsler Adult
                    Intelligence Scale For the detection of
                    neuropsychiatric dysfunction).

        8.6  References


        9.1  Acute poisoning

             9.1.1  Ingestion

                    After ingestion of sublethal doses, symptoms
                    may develop several hours after ingestion. Vomiting,
                    nausea and numbness of lips, are followed by abdominal
                    pain, brisk reflexes, tachycardia and
                    electrocardiographic changes. Dyspnoea, cyanosis,
                    peripheral vascular collapse, convulsions, coma and
                    respiratory paralysis can occur. Dizziness and ataxia
                    are common.  Illusions, delusions and neuropsychiatric
                    changes can appear between the 2nd and 5th day.
                    Acute poisoning is associated with psychiatric and
                    neurological signs and symptoms such as extreme
                    irritability, uncontrolled anger, rapid mood changes
                    including manic delirium and hallucinations, paranoid
                    ideas and suicidal tendencies, and memory defects. 
                    Convulsions, coma, and cardiac and respiratory arrest
                    may occur in severe poisoning.

             9.1.2  Inhalation

                    Acute inhalation produces rapid onset of both
                    local irritation and CNS symptoms ranging from
                    pharyngitis, nausea, vomiting, dizziness, headache,
                    delirium, hallucination, convulsions, coma and death
                    (Ellenhorn and Barceloux, 1988). Inhalation of
                    concentrations over 4,800 ppm may produce coma or
                    death after a few inhalations.  If consciousness is
                    regained motor agitation and disorientation may
                    follow.  Direct irritant effects on the lungs are
                    frequent and characterized by cough, shortness of
                    breath and chest pain. Subtle changes in pulmonary
                    function are transient.
                    Psychiatric disturbances and disturbances of the
                    central and peripheral nervous systems are often late
                    sequelae following apparent recovery (ILO, 1983).
                    In less severe exposures local irritation, nausea,
                    vomiting and abdominal pain are followed by headache,
                    euphoria, hallucinations, manic delirium, paranoid
                    reactions and suicidal tendencies.

             9.1.3  Skin exposure

                    Local contact causes reddening, erythema and
                    pain, cracking and peeling of skin. Blistering and
                    chemical burns may result from severe exposure.
                    Contact dermatitis may result from prolonged exposure
                    to liquid or concentrated vapour.

             9.1.4  Eye contact

                    Splashes of carbon disulphide in the eye cause
                    mmediate and severe irritation that may lead to
                    chemical burns of the cornea.

             9.1.5  Parenteral exposure

                    No data available.

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    No data available.

             9.2.2  Inhalation

                    The initial feature may include: headache,
                    malaise, visual disturbances, anaemia, fatigue,
                    anorexia, dysesthesia or paraesthesiae and trigeminal
                    neuralgia.  This may be followed by weight loss,
                    psychosis, and a polyneuropathy characterised by
                    diminished or absent Achilles and atellar reflexes,
                    sensory disturbances in a glove-stocking distribution,
                    peripheral nerve conduction defects.  Other
                    disturbances included myopathy of the calf muscle.
                    Optic neuritis and impairment of other cranial nerves
                    such as VIIth pair may also occur.  Hyper- and
                    hypoacidic gastritis and duodenal ulceration are a
                    common finding (WHO, 1979).
                    The classification of different syndromes quoted by
                    WHO (WHO, 1979) includes:
                    Atherosclerotic vasculoencephalopathy; the principal
                    forms being bulbar-paralytic, hemiplegic, or

                    The typical mental deterioration has been called an
                    organic psychosyndrome, which may be due to general
                    cerebral atherosclerosis, to direct toxicity. or to
                    The adverse effects on the vascular system is
                    widespread,involving cerebral, ocular, coronary and
                    renal vessels, myocardial infarction, nephrosclerosis
                    and retinal microaneurysm may be present.
                    Arterial hypertension, elevation of serum cholesterol 
                    (not cholesterol esters) and renal damage may occur
                    Impaired sexual function and cases of hypothyroidism
                    have been reported.
                    The classical picture of carbon disulphide poisoning
                    with encephalopathy, psychosis, polyneuritis is very
                    seldom observed nowadays.

             9.2.3  Skin exposure

                    Carbon disulphide liquid may be absorbed
                    through the skin but there are no reports of chronic
                    poisoning by this route of exposure.

             9.2.4  Eye contact

                    Only local irritation may occur.

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             After acute severe poisoning there may be rapid onset of
             coma followed by death due to respiration failure.
             Neurological sequelae are common in patients who survive.
             Chronic carbon disulphide poisoning is more common than cute
             poisoning, and occurs after prolonged exposures to
             concentrations usually over 30 units.  Neuropsychiatric
             disorders, hyperaesthesiae, parkinsonism and polyneuropathy

             follow the initial symptoms of skin "formication" (crawling
             sensation), weakness and malaise, although the most marked
             variety of neurological signs and symptoms may occur
             (Gosselin et al., 1984).
             Neurological complications are usually irreversible.
             Chronic intoxication has been strongly associated with
             increased cardiovascular mortality, early arteriosclerosis
             and hypertension.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Coronary heart disease is one of the main
                    concerns in workers exposed for years to 10 - 30 ppm. 
                    Increased mortality due to ischaemic heart disease has
                    been reported in exposed workers (CEC, 1988).
                    Relatively modest exposure to carbon disulphide may
                    raise low density lipoprotein-cholesterol
                    concentration and diastolic blood pressure (Egeland et
                    al., 1992).
                    Carbon disulphide causes vasoconstriction (especially
                    in the arteries of the upper and lower
                    Hypertension has also been observed.

             9.4.2  Respiratory

                    Carbon disulphide is an irritant to the
                    respiratory system.  Transient inflammation in small
                    airways causes mild ventilation-perfusion alterations
                    and air trapping  (changes in vital capacity and
                    arterial pO2 are observed). Pulmonary changes are
                    usually transient (CEC,1988).

             9.4.3  Neurological


                             In acute poisoning, CNS symptoms may
                             range from headache, dizziness, agitation,
                             euphoria, and aggressive behaviour to
                             unconsciousness, and even death resulting
                             from respiratory failure.

                             In chronic poisoning the first signs are
                             psychological: restlessness, excitation and
                             loss of temper, mood changes, lethargy. 
                             Gradually, the patient becomes depressed,
                             anxious, paranoid with suicidal tendencies. 
                             Nightmares and apathy are also present. 
                             Illusions and delusions may appear and there
                             may be daytime somnolence and nocturnal
                             In the further course of chronic
                             intoxication, neurological signs become more
                             prominent.  Both diffuse cortical and focal
                             symptoms from damage to the subcortical grey
                             matter and extrapyramidal system are typical. 
                             Symptoms of Parkinsonism appear:
                             bradykinesia, bradylalia, muscle rigidity,
                             tremor and increased elementary postural
                             In chronic intoxication, statokinesiometry
                             has shown postural stability disorder in 73%
                             of  a group of 37 patients studied. Balance
                             disorders detected by means of this test
                             showed high compatibility with results of
                             electronystagmography which confirmed damage
                             of the central part of vestibular system due
                             to carbon disulphide intoxication (Sulkowski
                             et al., 1992).

            Peripheral nervous system

                             The earliest clinical signs are
                             distal sensory abnormalities, numbness and
                             mild anaesthesia  (CEC, 1988).  The typical
                             sign of carbon disulphide intoxication in man
                             is a toxic polyneuropathy.  Distribution  of
                             the abnormalities is mostly symmetrical, and
                             objectively there is hyporeflexia.
                             A decrease in conduction velocity of slow
                             motor fibres occurs at low levels of exposure
                             to carbon disulphide (Ruijten et al.,
                             Cranial nerves are affected.  Optic neuritis
                             with visual disturbances, changes in colour
                             perception, scotomata, and constriction of
                             the visual fields have been observed.

                             Exposure to carbon disulphide can also impair
                             hearing ability.  Audiometric examinations in
                             workers shows evidence of nerve deafness and
                             also a decreased ability to distinguish sound
                             intensity within the range 1.5-3.0

            Autonomic nervous system

                             Neurasthenic syndrome with autonomic
                             nervous system disturbance is

            Skeletal and smooth muscle

                             Amyotrophy has been described in the
                             triceps sural and quadriceps muscles of the
                             legs, as well as in the small muscles of the
                             hand, the thenar, the hypothenar and in the
                             interosseal muscles (WHO, 1979).

             9.4.4  Gastrointestinal

                    In acute poisoning nausea, vomiting and
                    abdominal pain occur.  In chronic poisoning dyspepsia
                    and gastritis  (atrophic), and duodenal ulceration
                    have been described  (Gosselin et al., 1984).

             9.4.5  Hepatic

                    Liver damage is not a prominent feature but an
                    enlarged, tender liver may be observed (Gosselin et
                    al., 1984).  Chronic exposure may produce
                    centrilobular hepatic necrosis (Ellenhorn and
                    Barceloux, 1988).

             9.4.6  Urinary


                             Some reports have drawn attention to
                             nephrosclerosis in autopsies of patients but
                             this could be ascribed to a general
                             atherosclerotic process induced by carbon
                             Chronic renal dysfunction with abnormal
                             creatinine clearances may be seen after
                             long-time, low-level occupational exposure
                             (Gosselin et al., 1984).


                             No data available.

             9.4.7  Endocrine and reproductive systems

                    Carbon disulphide causes several disturbances
                    of the endocrine system (WHO, 1979):
                    -  a reduction of adrenal activity
                    -  a reduction of the endocrine activity of the
                       testis and impairment in spermatogenesis
                       possibly due to direct gonadal damage, with
                       decreased libido and potency.  There is
                       decreased in 17-ketosteroids,
                       17-hydroxycorticosteroids and androsterone in
                       the urine.  Urinary excretion of testosterone
                       and gonadotropin luteinizing hormone is also
                    -  hormonal disturbances in women, resulting in
                       menstrual irregularities, spontaneous
                       abortion and premature births
                    -  impairment of thyroid function, which could
                       be primary or due to a deficiency in TSH or
                       the TSH-releasing factor or both.
                    The most common complaints are loss of libido and
                    menstrual disorders (Gosselin et al., 1984).

             9.4.8  Dermatological

                    Liquid carbon disulphide is a severe irritant
                    of both the skin and mucosa. Blisters and more severe
                    burns have been observed in viscose rayon workers. 
                    Degenerative changes in the local peripheral nerves
                    has been observed after skin contact (Davidson &
                    Fenliebs, 1972).

             9.4.9  Eye, ears, nose, throat: local effects

                    Chronically exposed workers have an increased
                    incidence of retinal microaneurysms (Gosselin et al.,
                    Retinopathy, eye damage with blind spots, narrowing of
                    vision and decreased ability to see in the dark may
                    occur as early effects of exposure (CEC, 1988).

                    Contact lenses should not be worn when working with
                    carbon disulphide (OSHA, 1978).

             9.4.10 Haematological

                    A moderate decrease in the haemoglobin
                    concentration and erythrocyte count was reported in
                    workers exposed to carbon disulphide. Increased
                    platelet aggregationand increase in thromboplastin has
                    been reported (EHC, 1979).

             9.4.11 Immunological

                    No data available.

             9.4.12 Metabolic

           Acid-base disturbances

                             May be secondary to severe respiratory
                             or cardiovascular disturbances.

           Fluid and electrolyte disturbances

                             May result from respiratory and
                             cardiovascular disturbances.


                             Carbon disulphide causes decreased
                             glucose tolerance and may also elevate
                             bloodcholesterol levels.

             9.4.13 Allergic reactions

                    No data available.

             9.4.14 Other clinical effects

                    No data available.

             9.4.15 Special risks

                    Pregnancy: In a study of women exposed to
                    carbon disulphide (30 ppm) there was a higher
                    incidence of spontaneous abortion and premature births
                    than in the control group.

                    Breast feeding: Carbon disulphide has been found in
                    the breast milk of mothers occupationally exposed to
                    levels up to 12.3 mg/m3 (cited in CEC, 1988).

        9.5  Others

             There is an inborn error of metabolism manifesting
             itself as an abnormal iodine-azide reaction in subjects
             working under a high or moderate carbon disulphide exposure.
             This test is used to screen workers exposed to carbon
             With increasing occupational exposure to carbon
             disulphide,low density lipoprotein(LDL)-cholesterol and
             apolipoproteins A1 and B rose, while high density
             ipoprotein(HDL)-cholesterol, HDL-cholesterol/apolipoproteine
             A1 and LDL-cholesterol/apolipoprotein B ratios decreased
             significantly  (Vanhoorne et al., 1992).

        9.6  Summary


        10.1 General principles

             The patient should be removed from exposure and
             decontaminated.  Clothing should be removed and the skin
             thoroughly washed with soap and water. In the case of eye
             contact irrigate thoroughly with water. Give appropriate
             symptomatic and supportive measures.
             Provide symptomatic treatment.
             There is no specific antidote.
             Because of the risk of delayed sequelae adequate follow up
             should be provided.

        10.2 Life supportive procedures and symptomatic treatment

             In all acute exposures, maintain a clear airway, give
             oxygen and assist respiration if necessary.

        10.3 Decontamination

             If carbon disulphide has contaminated lips or mouth, or
             has been ingested, rinse lips and mouth thoroughly with
             water. Following recent ingestion do not induce vomiting but
             perform gastric aspiration and/or lavage.

             In the case of skin contamination, remove contaminated
             clothing, wash with copious amounts of water.
             If eyes are contaminated, irrigate for at least 15 minutes
             with room-temperature water and seek ophthalmologist's
             advice. Contact lenses may be affected by the solvent and
             impede eye decontamination (CEC, 1988).

        10.4 Enhanced elimination

             No measures are known to be effective in enhancing
             elimination of carbon disulphide.

        10.5 Antidote treatment

             10.5.1 Adults


             10.5.2 Children


        10.6 Management discussion

             Many management recommendations such as large doses of
             vitamin B6 and I.V. urea (1.5 mg/kg) are based on the
             findings of old studies.  However, their efficiency in carbon
             disulphide poisoning has not been established and further
             research is needed.


        11.1 Case reports from literature

             Tolonen studied 97 men exposed to carbon disulphide at
             levels of 60 - 125 mg/m3 over 15 years.  He compared the
             incidence of heart disease, psychological impairment and also
             the nerve conduction velocity with those in 96 controls. 
             Twice as many exposed men had abnormalities and combined
             disorders occurred more frequently in the exposed group e.g.
             a combination of 3 abnormalities was 3 times more frequent in
             the exposed group than in controls.
             Spyker et al (1982) reported the symptoms found in 27
             individuals who had to manage a railway tank-car which caught
             fire.  Seven appeared to be severely ill and four had
             shortness of breath and chest pain.

             The symptoms found were: headache (59%), dizziness (59%),
             nausea (52%), burning of throat, lips or skin (40%),
             shortness of breath or chest pain (15%), impotence (7%) and
             vomiting (4%).  Headache and dizziness were the predominant
             signs, indicative of CNS effects.  Vital capacity studies and
             pO2 measurements showed a mild ventilation-perfusion
             abnormality and air trapping.


        12.1 Specific preventive measures

             Exposure should be avoided by pregnant or lactating
             women and by subjects with a history of psychiatric
             disturbance, neurological, cardiac, renal, pulmonary, liver
             and endocrine disorders.
             Since screening of workers normally involves the iodine azide
             reactions, workers with a positive test under control
             conditions should generally not be occupationally exposed to
             carbon disulphide.

        12.2 Other

             No data available.


        ACGIH - American Conference of Governmental Industrial
        Hygienists  (1986).  "Documentation of the threshold limit values
        for chemical substances in the workroom environment".
        British Crop Protection Council (1987).  The Pesticide Manual, a
        World Compendium, 8th Ed.
        Commission of the European Communities (CEC) (1988).  Solvents in
        Common Use.
        Davidson M, Fenliebs M (1972).  Carbon disulphide poisoning: a
        review. Am Heart J 83(1); 100-114.
        De Matteis E, Seawright AA (1973).  Oxidative metabolism of carbon
        disulphide by the rat.  Effect of treatments which modify the
        liver toxicity of carbon disulphide.  Chem Biol Interact
        7: 375-388.
        Egeland GM, Burkhart GA, Schnorr TM et al (1992) Effects of
        exposure to carbon disulphide on low density lipoprotein
        cholesterol concentration and diastolic blood pressure. Br. J.
        Ind. Med. 49: 287 - 293.

        Ellenhorn MJ, Barceloux DG (1988). Medical Toxicology, Diagnosis
        and Treatment of Human Poisoning. Elsevier, Amsterdam.
        Environmental Health Criteria No.10:  Carbon Disulphide (1979). 
        WHO, 1979.
        Gosselin RE, Smith RP, Hodge HC (1984).  Clinical Toxicology of
        Commercial Products, 5th Ed.  Williams & Wilkins; III: 90-94.
        Greenwood NN, Earnshaw A (1984).  Chemistry of the Elements,
        Pergamon Press.
        International Labour Office (ILO) (1983).  Encyclopedia of
        Occupational Health and Safety, 3rd Ed.
        Lazarev et al (1965).  On possible adverse reactions following use
        of some drugs by persons handling carbon disulphide.  Gig Tr Prof
        Zabol; 9: 24-27.
        National Institute of Occupational Safety and Health (NIOSH) 
        (1986).  Registry of toxic effects of chemical substances (RTECS). 
        Publ. N  84-101-6, US Dept Health & Human Sciences.
        OSHA (1978). Occupational Safety and Health Association. OSHA,
        Washington DC.
        Ruijten MWMM, Salle HJA, Verberk MM, Muijser H (1990) Special
        nerve functions and colour discrimination in workers with long
        term low level exposure to carbon disulphide. Br. J. Ind. Med. 
        47: 589 - 595.
        Spyker DA et al (1982).  Health effects of acute carbon disulphide
        exposure.  J Toxicol & Clin Toxicol 19(1): 87
        Sulkowski WJ, Kowalska S, Sobczak Z, Jozwiak Z (1992) The
        statokinesiometry in evaluation of the balance system in persons
        with chronic carbon disulphide intoxication. Pol. J. Occup. Med.
        Environ. Health. 5: 265 - 276.
        Vanhoorne M, De Bacquer D, De Backer G (1992) Epidemiological
        study of the cardiovascular effects of carbon disulphide. Int. J.
        Epidemiol. 21: 745 - 752.


        Authors:    Dr Patricia Dorfman and Dr Julia Higa de Landoni
                    Servicio de Toxicologia
                    Hospital de Clinicas "José de San Martin"
                    Cordoba 2351
                    1120    Buenos Aires
                    Tel: 54-1-8250480
                    Fax: 54-1-3318605
        Date:       April 1990
        Reviewer:   Dr A. Nantel
                    Centre de Toxicologie du Québec
                    Centre Hospitalier de l'Universite Laval
                    2705 bld. Laurier
                    Québec City
                    Québec G1V 4G2
                    Tel: 1 418 654 2254
                    Fax: 1 418 654 2754
        Date:       November 1990
        review:     Adelaide, Australia, April 1991
        Update:     Dr R. Fernando, June 1993

    See Also:
       Toxicological Abbreviations
       Carbon disulfide (EHC 10, 1979)
       Carbon disulfide (ICSC)
       Carbon disulfide (FAO Meeting Report PL/1965/10/2)
       Carbon disulfide (FAO/PL:1967/M/11/1)
       Carbon disulfide (FAO/PL:1968/M/9/1)
       Carbon disulfide (WHO Pesticide Residues Series 1)
       Carbon Disulfide (CICADS 46, 2002)