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Monochloroacetic acid

1. NAME
   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 manufactures, main importers
2. SUMMARY
   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. PHYSICO-CHEMICAL PROPERTIES
   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. USES
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstances of poisoning
   4.3 Occupationally exposed population
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   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 and excretion
7. TOXICOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 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)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATION
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 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
9. CLINICAL EFFECTS
   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
      9.2.1 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.1 Inhalation
      9.2.1 Skin contact
      9.2.1 Eye contact
      9.2.1 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 Neurologic
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive system
      9.4.8 Dermatologic
      9.4.9 Eye, ear, noise, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunologic
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
10. MANAGEMENT
   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. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.1 Other
13. REFERENCES
14. AUTHOR, REVIEWERS



    MONOCHLOROACETIC ACID

    International Programme on Chemical Safety
    Poisons Information Monograph 352
    Chemical

    1.  NAME

        1.1  Substance

             Monochloroacetic acid

        1.2  Group

             Chlorinated organic acid.

        1.3  Synonyms

             Acetic acid, chloro-; chloracetic acid; 
             chloroacetic acid; alpha-chloroacetic acid; 
             chloroethanoic acid; monochloroacetic acid; MCA; MCAA; 
             monochloracetic acid; monochloroethanoic acid; 
             Acide chloracetique (Fr), Acide monochloroacetique (Fr); 
             Monochloressigsäure (Ger); Acidomonochloroacetico (Ita); 
             Monochloorazijnzuur (Dutch);

        1.4  Identification numbers

             1.4.1  CAS number

                    79-11-8

             1.4.2  Other numbers

                    EINECS 2011784

        1.5  Main brand names, main trade names

             MCA, Na-MCA (sodium salt).

        1.6  Main manufactures, main importers

             Akzo (The Netherlands), Atochem (France), Eka Nobel
             Skoghall AB (Sweden), Hoechst (Germany).

    2.  SUMMARY

        2.1  Main risks and target organs

             CNS, intracellular respiration, cardiac, respiratory,
             renal and skeletal muscles toxicity. Corrosive.

        2.2  Summary of clinical effects

             Solution, solid flakes and molten MCA are corrosive. MCA
             is extensively absorbed via mucous membranes and skin causing
             systemic poisoning. Symptoms may be delayed for some (1 to 4)
             hours. Vomiting, diarrhoea and CNS-excitability are early
             signs of poisoning followed by CNS-depression, coma and
             cerebral oedema. Severe myocardial depression and shock
             supervene due to nonspecific myocardial damage. Severe
             metabolic acidosis (lactic acidosis) and hypokalemia appears
             within a couple of hours. Progressive renal failure is seen
             within 12 hours probably due to extensive myoglobinuria
             secondary to severe rhabdomyolysis.

        2.3  Diagnosis

             Monochloracetic acid concentration in serum.
             Acid base balance. Serum potassium.
             Development of metabolic acidosis indicates severe systemic
             poisoning. Hypokalaemia is a typical early sign.
             Serum calcium. Hypocalcaemia is secondary either to binding
             to oxalates or secondary to rhabdomyolysis.
             ECG-monitoring.
             Myoglobin in serum (and urine). Low urine pH increases the
             risk of kidney damage from myoglobin in urine.

        2.4  First-aid measures and management principles

             After ingestion gastric decontamination.
    
             After skin exposure 1) immediate and prolonged flushing with
             copious amounts of water even under the clothes, 2) remove
             contaminated clothing, 3) continue flushing for at least 15
             minutes.
    
             After eye exposure immediate flushing with water for 15
             minutes.
    
             After inhalation fresh air, oxygen and other treatment as for
             irritant gases.
    

             Symptomatic therapy in systemic poisoning (fluid replacement,
             correction of metabolic acidosis and hypokalaemia, adequate
             urine production and alkalinization of urine to avoid
             myoglobin precipitation in renal tubulus, inotropic therapy
             in cardiac failure, cerebral oedema treatment). If available,
             Dichloroacetic acid (DCA), buffered to 7.2, should be given,
             50 mg/kg as slow intravenous injection or infusion,
             preferably prior to the onset of lactic acidosis, in all
             cases with more than 5% body surface contamination. Repeat
             after two hours.
             If no DCA is available, phenobarbitone in high dosages,
             sufficient to cause deep pre-coma, might be attempted if
             respiratory support can be given, and/or hemodialysis should
             be performed.
    
             N-Acetylcysteine and/or ethanol, as recommended in some
             previous publications, is probably useless. Plasmapheresis
             may be considered in severe rhabdomyolysis.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             MCA is produced by a reaction under pressure between
             chlorine and acetic acid (Budavari, 1996).

        3.2  Chemical structure:

             Molecular Formula: ClCH2-COOH
    
             Molecular weight: 94.5

        3.3  Physical properties:

             3.3.1  Colour

                    At temperature <19°C: colourless or white
                    deliquescent crystals

             3.3.2  State/Form

                    solid-crystals
                    solid-flakes
                    solid-powder
                    liquid-other

             3.3.3  Description

                    At temperature <19°C: colourless or white
                    deliquescent crystals
                    At temperature >19°C: liquid
    
                    In industry different physical forms of MCA are
                    used:
    
                    Molten at approximately 60°C (transportation in
                    heating tanks)
                    Aqueous solution (often 80% concentration, heated to
                    35°C)
                    Flakes
                    MCA sodium salt, a white powder  (Hommel 1980,
                    Budavari 1996).
    
                    Odour - penetrating, burning
                    Odour threshold 0.045 ppm
                    Calculation factors:  1 ppm = 3.86 mg/m3
                    1 mg/m3 = 0.20 ppm
    
                    pH<1 for 80% aqueous solution
    
                    pKa: 2.82 (is a stronger acid than acetic acid - pKa
                    4.75)
    
                    Dissociation constant: Ka 1.5 M at 25°C
    
                    Viscosity (100°C): 1.9 mPa  (the 80% solution
                    solidifies at 19°C)
    
                    Specific gravity: 1.27 at 25°C for 80% aqueous
                    solution, 1.40 at 20°C for flakes
    
                    Solubility: very soluble in water (at 25°C 84
                    weight%), soluble in alcohol, methanol, acetone,
                    carbon, disulphide, benzene, chloroform, ether.
                    Slightly soluble in hydrocarbons and chlorinated
                    hydrocarbons
    
                    Melting point: 61 to 63°C
    
                    Boiling point: 143°C for 80% aqueous solution, 189°C
                    for flakes
    
                    Flammable point (flash point): 118°C for 80% aqueous
                    solution, 126°C for flakes
    
                    Vapour density (air=1): 0.03
    

                    Vapour pressure: 17.8 mm Hg at 25°C for 80% aqueous
                    solution, 0.20 mm Hg at 25°C for flakes
    
                    Relative vapour density (air=1): 3.3
    
                    (Hommel 1980, Huismanss et al 1980, Budavari
                    1996, RTECS 1986, Weast 1978-9).

        3.4  Hazardous characteristics

             Hazardous decompostion products include oxides of carbon
             as well as ionic or oxidised chlorine.
    
             Incompatablities: strong bases, oxidising agents and most
             common metals.

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    MCA is widely used in chemical industries as
                    intermediates in the synthesis of
                    carboxymethylcellulose, phenoxyacetic acid,
                    thioglycolic acid, glycine, indigoid dyes and others.
                    MCA is stored and transported as flakes or as an 80%
                    aqueous solution in transport tanks at 35°C (it
                    solidifies at 19°C). It may also be desolved in
                    ethanol or methanol. The sodium salt, Na-MCA, is
                    usually transported as white granule in paper bags
                    with polyethylene coating. (Hommel 1980, Budavari
                    1996).

        4.2  High risk circumstances of poisoning

             When handling and transporting MCA, especially molten
             and solutions; skin contamination is the most common cause of
             systemic poisoning.

        4.3  Occupationally exposed population

             Workers at plants producing and using MCA. Transport
             workers when filling and emptying MCA in tankers.

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Ingestion of MCA produces corrosive damage and systemic
             poisoning
    
             The sodium salt (Na-MCA) is also absorbed and causes
             poisoning.
    
             (Huismans et al., 1986; Gosselin et al., 1984; RTECS 1986;
             Woodard 1941; Feldham et al 1993; Rogers 1995).

        5.2  Inhalation

             Inhalation of MCA fumes or aerosols will cause damage
             similar to other irritant gases. Systemic poisoning may also
             occur (Zeldenrust,1951).

        5.3  Dermal

             MCA is corrosive to skin and will penetrate damaged and
             even apparently undamaged skin producing systemic poisoning
             (Contassot et al., 1987; Kulling et al., 1992; Kusch et al.,
             1990; Vincenti, 1987).
    
             The sodium salt, Na-MCA, is not corrosive as such and does
             not penetrate skin (Nyström,1986; Andersson, 1992).

        5.4  Eye

             MCA is corrosive to eyes (Grant, 1986).

        5.5  Parenteral

             Parenteral administration of MCA in experimental animals
             is quickly lethal at dosages comparable to oral and dermal
             lethal dosages. No human data are available.(Huismanss et
             al., 1986).

        5.6  Others

             No data available

    6.  KINETICS

        6.1  Absorption by route of exposure

             MCA and Na-MCA are readily absorbed after ingestion
             (Huismans et al., 1986; Maksimov & Dubinina, 1974; RTECS,
             1986; Woodard et al., 1941). MCA is also absorbed very
             quickly through the skin (Contassot et al., 1987;  Kulling et
             al., 1992; Kusch et al., 1990; Vernont et al., 1977;
             Vincenti, 1987).

        6.2  Distribution by route of exposure

             Animal studies indicate accumulation in liver and
             kidneys, followed by accumulation in the brain several hours
             later (Hayes et al., 1973; Bhat et al., 1983).

        6.3  Biological half-life by route of exposure

             Elimination is of first order kinetics (biphasic)
             t´ blood  approx 2 hours (Kulling et al., 1992).
             t´ (elimination) 15 hours (Dancer et al., 1965).

        6.4  Metabolism

             It has been suggested that MCA binds to
             gluthathione-S-transferase (GST) rather than to glutathione
             (Dierckz, 1984), while others suggest that MCA binds to
             glutathione or other sulfhydryl containing substances
             (Dalgaard-Mikkelsen et al., 1955; Fuhrman et al., 1955;
             Gosselin et al., 1984; Hayes et al., 1973; Hirade et al.,
             1950; Huismanss et al., 1986; Yllner, 1971). Another author
             suggests that the main metabolites (in mice) were
             non-conjugated S-carboxymethyl cysteine, thio-diacetic acid,
             and some glycolic acid and suggests the following metabolic
             pathway for chloroacetate in mice:
    
             CH2Cl-COOH      -->  (CH2OHCOOH         --> (CO2
                 MCA              glycolic acid
                  '                    '
    
                                      COOH-COOH          "CH2NH2COOH"
                                      oxalic acid
    
              "G-S-CH2COOH               S-carboxymethyl glutathione"
                    '
              HOOC-CH(NH2)CH2SCH2COOH    S-carboxymethyl cysteine
                    '
              HOOC-CH2-S-CH2-COOH        thio-diacetic acid
    

             Compounds in "  "  were not isolated (Huismanss et al., 1986,
             Yllner, 1971)
    
             Glycolic acid is metabolised in man to glyoxylic acid, which
             is metabolised to formic acid, glycine and oxalic acid
             (Jacobsen et al 1984).

        6.5  Elimination and excretion

             In one human case the majority of MCA was excreted as
             nonmetabolized MCA. A minor part reacted with glutathione and
             was excreted in urine as the conjugate. A small amount was
             metabolized and excreted as carbon dioxide in exhaled air
             (Dancer et al., 1965).
    
             In mice 80-90% of administered MCA was excreted in urine
             within 24 hours, probably as metabolites, 8% was excreted via
             exhaled air as CO2 (Yllner, 1971).

    7.  TOXICOLOGY

        7.1  Mode of action

             MCA is corrosive to skin, mucous membranes and eyes.
             (Contassot et al., 1987; Gosselin et al., 1984; Kulling et
             al., 1992; Maksimov & Dubinina, 1974; Millischer and Ruty,
             1986; Sax, 1984; Grant, 1986). MCA also penetrates the skin,
             especially damaged skin (Contassot et al., 1987; Kulling et
             al., 1992; Kusch et al., 1990).
    
             The ethylester of MCA may cause skin sensitisation (Braun &
             van der Walle, 1987; Huismanss et al., 1986).
    
             After absorption MCA blocks the cell energy supply probably
             by decreasing the activity of pyruvate dehydrogenase and to
             some extent of  ketoglutarate dehydrogenase leading to lactic
             acidosis (van Hinsbergh 1994). Lactic acid is accumulated in
             the cerebrospinal fluid (Mitroka 1989). MCA damages the blood
             brain barrier (Berardi et al., 1987; Mitroka, 1989). The
             underlying gross mechanism of MCA toxicity is probably
             microvascular damage, due to endothelial cellular damage.
    
             Some of the metabolites are toxic like glycolic acid
             (metabolic acidosis) and oxalates which may induce kidney and
             CNS toxicity

             In vitro, MCA blocks the cell energy supply in an as yet
             incompletely resolved manner, leading to a gradual decrease
             in ATP generation and in protein synthesis. Supplementation
             of intermediates of the Krebs-cycle or of acetyl-donors does
             not reduce this effect whereas incubation with the sodium
             salt of MCA causes a slow but marked decrease in the activity
             of pyruvate dehydrogenase and to a lesser degree of 
             keto-glutarate dehydrogenase (van Hinsbergh, 1994).
    
             Former hypotheses of MCA toxicity:
             MCA and/or its metabolites were thought to act like
             fluoroacetic acid by blocking the tricarboxylic acid cycle
             (Krebs cycle) (Gosselin et al., 1984; Fuhrman et al., 1955;
             Gosselin et al., 1984; Hayes et al., 1973; Huismanss et al.,
             1986; Zenz, 1975).
    
             It was also thought that MCA probably reacts with sulfhydryl
             (-SH) groups in enzymes and other substances. MCA reduces
             sulfhydryl content in rat liver and kidney
             (Dalgaard-Mikkelsen et al., 1955; Fuhrman et al., 1955;
             Gosselin et al., 1984; Hayes et al., 1973; Hirade et al.,
             1950; Huismanss et al., 1986).

        7.2  Toxicity

             7.2.1  Human data

                     7.2.1.1  Adults

                     Skin exposure 
                     It can be difficult to determine at an early stage the
                     percentage of body burns, due to irregular or rather
                     blotchy vasoconstriction that seems to be typical of
                     MCA burns. 2 or 3 days later skin burns may be up to
                     50% larger than at first glance (Vincenti, 1987).
    
        up to 5% body surface                       possibly moderate 
        (80% solution)                              systemic poisoning
    
        6-10% body surface (molten 80°C)            severe, up to lethal
                                                    systemic poisoning
    
        approx 10% body surface                     moderate
        (90% solution)                              systemic
        (Kusch et al 1990)                          poisoning
    
        15% body surface (80% solution)             lethal 
        (Millischer and Ruty, 1986;                 systemic
        Contassot et al., 1987;                     poisoning
        Vincenti, 1987)

    
        25-30% body surface (80% solution)          lethal 
        (Kulling et al., 1992)                      systemic
                                                    poisoning
    
        unknown % body surface                      lethal 
        + inhalation                                systemic 
        (von Oettingen, 1958;                       poisoning
        Zeldenrust, 1951)

                     7.2.1.2  Children

                              No data available

             7.2.2  Relevant animal data

                    Prolonged inhalation of MCA vapours in rats
                    induced breathing difficulties, decreased oxygen
                    consumption, haemoconcentration and inflammatory
                    reaction of the bronchial tree (Maksimov & Dubinina,
                    1974).
    
                    LD50 MCA (oral) (rat, mouse) 55 to165 mg/kg (Hayes et
                    al., 1973; Huismanss et al., 1986; Maksimov &
                    Dubinina, 1974; RTECS 1986; Woodard et al., 1941).
    
                    LD50 MCA (oral) (mouse) 260 mg/kg (Berardi et al.,
                    1987).
    
                    LD50 Na-MCA (oral) (rat, mouse, guinea pig) 76.2 to
                    255 mg/kg (Huismanss et al., 1986; Maksimov &
                    Dubinina, 1974; Woodard et al., 1941).
    
                    LD50 MCA (skin, rabbit) 230 mg/kg (Vernot et al.,
                    1977).
    
                    In one study degeneration of Purkinje cell nuclei was
                    noted probably indicating blood-brain barrier damage
                    (Berardi et al., 1987).

             7.2.3  Relevant in vitro data

                    In vitro studies have shown that MCA toxicity
                    still occurs in spite of incubation of the cells with
                    acetate or acetate donors (van Hinsbergh,
                    1994).

             7.2.4  Workplace standards

                    1 mg/m3 (OEL-Russia STEL 1993); 
                    8-hr TWA: 0.3 ppm, skin (AIHA 1996)
                    Ceiling or short-term TWA: 1 ppm, 15 min (ACGHI
                    1986)

             7.2.5  Acceptable daily intake (ADI)

                    Unknown.

        7.3  Carcinogenicity

             One study indicated no carcinogenicity (van Duuren et al
             1974).
             National Toxicology Program (USA): not carcinogenic to mice
             and rats (NTP, 1992; de Angelo et al., 1997).

        7.4  Teratogenicity

             Unknown.

        7.5  Mutagenicity

             According to National Toxicology Program (USA) MCA is
             not genotoxic (Tennant et al., 1990).

        7.6  Interactions

             Unknown.

    8.  TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATION

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                              For analysis of MCA in the blood
                              take 10ml blood (heparinised tube), take away
                              plasma, freeze for later analysis. Take
                              series of samples.

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple Qualitative Test(s)

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                    8.2.1.3  Simple Quantitative Method(s)

                    8.2.1.4  Advanced Quantitative Method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                    8.2.2.2  Advanced Qualitative Confirmation Test(s)

                    8.2.2.3  Simple Quantitative Method(s)

                    8.2.2.4  Advanced Quantitative Method(s)

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum
                              "Basic analyses"
                              "Dedicated analyses"
                              "Optional analyses"

                    8.3.1.2  Urine
                              "Basic analyses"
                              "Dedicated analyses"
                              "Optional analyses"

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses
                    "Basic analyses"
                    "Dedicated analyses"
                    "Optional 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

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    MCA and Na-MCA produce systemic poisoning.
    
                    Symptoms of systemic poisoning may be delayed for some
                    (1 to 4) hours.
    
                    Vomiting and diarrhoea are early signs of systemic
                    poisoning.
    
                    CNS-excitability with disorientation (an early sign of
                    systemic poisoning), delirium and convulsions followed
                    by CNS-depression and coma. Cerebral oedema. Typical
                    initial sign is alteration of CNS-excitation and
                    CNS-depression.
    

                    Severe myocardial depression, shock, arrhythmias
                    (atrial tachycardia, ventricular
                    tachycardia-fibrillation), ECG changes indicative of
                    nonspecific myocardial damage.
    
                    Progressive renal failure starting within 12 hours
                    leading to anuria.
    
                    Hypokalaemia during the first 24 hours. Severe
                    metabolic acidosis starting within a couple of hours.
                    Hypocalcaemia (may be delayed for 1 to 2 days), high
                    creatine kinase (CK) values as well as AST and ALT as
                    signs of extensive tissue damage affecting skeletal
                    muscles, heart, and brain. Myoglobinaemia and
                    leucocytosis may occur
    
                    The proposed inhibition of pyruvate dehydrogenase
                    activity will cause impaired energy production in
                    cells leading to severe cell damage of especially
                    energy rich organs such as brain, skeletal muscle and
                    heart, and causing metabolic acidosis.
    
                    Blood brain barrier damage increases intracerebral
                    lactic acidosis.
    
                    The acidosis is mainly due to accumulation of lactic
                    acid but may also be due to the formation of glycolic
                    acid. Renal impairment might be due to the toxic
                    action of MCA (as to other organs) but may also be
                    secondary to myoglobin and oxalate precipitation in
                    the tubuli. Binding of calcium to oxalates probably
                    causes the hypocalcaemia, but hypocalcaemia can also
                    be secondary to rhabdomyolysis.
    
                    (Kulling et al., 1992)

             9.1.2  Inhalation

                    Irritant - risk of toxic pulmonary oedema.
                    Probably risk of systemic poisoning as for
                    ingestion.
    
                    (Kulling et al., 1992)

             9.1.3  Skin exposure

                    Liquid: Irritant and corrosive (1st - 2nd
                    degree burns) and high risk of systemic poisoning if
                    >6% of body surface exposed is affected. MCA is
                    rapidly absorbed even through intact skin. Typical
                    skin lesion: hyperaemia with a central white zone
                    (perhaps due to vasoconstriction). Systemic poisoning
                    as for ingestion.
    
                    Solid MCA: flakes of MCA are very corrosive when they
                    come in contact with water i.e. moist skin or mucous
                    membranes; molten MCA (>60°C) is also corrosive. Both
                    give 3rd degree burns, risk of systemic poisoning as
                    for liquid (if >1% of body surface is affected),
                    which however is less likely to occur.
    
                    (Kulling et al., 1992)

             9.1.4  Eye contact

                    Liquid and solid MCA will cause corrosive damage.
    
                    (Kulling et al., 1992)

             9.1.5  Parenteral exposure

                    Not known.

             9.2.1  Other

                    Not known

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    No data available.

             9.2.1  Inhalation

                    No data available.

             9.2.1  Skin contact

                    No data available.

             9.2.1  Eye contact

                    No data available.

             9.2.1  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             Systemic poisoning is usually severe and carries a poor
             prognosis. Hypokalaemia may occur during the first 24 hours.
             Severe metabolic acidosis starts within a couple of hours.
             Hypocalcaemia (may be delayed for 1-2 days), high creatine
             kinase (CK) values as well as AST and ALT are signs of
             extensive tissue damage (skeletal muscles, heart, brain).
             Myoglobinaemia and leucocytosis may also occur. The cause of
             death is cardiac insufficiency/arrhythmias, renal failure,
             and cerebral oedema
             (Kulling et al., 1992).

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Severe myocardial depression, shock,
                    arrhythmias (atrial tachycardia, ventricular
                    tachycardia-fibrillation), ECG changes indicative of
                    nonspecific myocardial damage. (Contassot et al.,
                    1987; Feldhaus et al., 1993; Kulling et al., 1992;
                    Kusch et al., 1990; Millischer & Ruty, 1986; Rogers,
                    1995; Vincenti, 1987).

             9.4.2  Respiratory

                    Local mucous membrane damage, pulmonary oedema
                    probably after MCA inhalation/aspiration (Zeldenrust,
                    1951).

             9.4.3  Neurologic

                    9.4.3.1  CNS

                             Anxiousness, excitability,
                             CNS-depression, coma, seizures, cerebral
                             oedema after a few hours delay (Contassot et
                             al., 1987; Kulling et al., 1992; Millischer
                             and Ruty; 1986).

                    9.4.3.2  Peripheral nervous system

                             No symptoms reported.

                    9.4.3.3  Autonomic nervous system

                             No symptoms reported.

                    9.4.3.4  Skeletal and smooth muscle

                             Rhabdomyolysis (Kulling et al.,
                             1992; Millischer and Ruty, 1986).

             9.4.4  Gastrointestinal

                    Nausea, vomiting, diarrhoea (Kulling et al.,
                    1992; Kusch et al., 1990; Millischer and Ruty, 1986;
                    Vincenti, 1987).

             9.4.5  Hepatic

                    Elevation of transaminases after 1 to 2 days
                    (Kulling et al., 1992; Millischer and Ruty,
                    1986).

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Tubular necrosis, progressive renal
                             insufficiency (Kulling et al., 1992;
                             Millischer and Ruty, 1986).

                    9.4.6.2  Others

             9.4.7  Endocrine and reproductive system

                    No symptoms reported.

             9.4.8  Dermatologic

                    Corrosive damage (1st-3rd degree burns)
                    (Contassot et al., 1987; Kulling et al., 1992; Kusch
                    et al., 1990; Millischer and Ruty, 1986). Typical skin
                    lesion: hyperaemia with a central white zone (Kulling
                    et al., 1992; Millischer and Ruty, 1986).

             9.4.9  Eye, ear, noise, throat: local effects

                    Probably corrosive damage.

             9.4.10 Haematological

                    Leucocytosis (Kulling et al., 1992).

             9.4.11 Immunologic

                    No symptoms reported.

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Severe metabolic acidosis
                             (Contassot et al., 1987; Feldhaus et al.,
                             1993; Kulling et al., 1992; Millischer and
                             Ruty, 1986; Rogers, 1995) mainly due to
                             lactic acid accumulation.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Skin damage may cause fluid loss.
                             In the initial phase hypokalaemia occurs,
                             (Kulling et al., 1992; Kusch et al., 1990; 
                             Millischer and Ruty, 1986). Hypocalcaemia is
                             seen after some hours delay (Kulling et al.,
                             1992).

                    9.4.12.3 Others

                             Multi organ effects have been seen
                             (increased creatine kinase activity,
                             increased transaminases) (Kulling et al.,
                             1992; Millischer and Ruty, 1987).

             9.4.13 Allergic reactions

                    Allergy has been induced by the ethylester of
                    MCA but not by MCA alone (Braun & van der Walle, 1987;
                    Huismanss et al., 1986).

             9.4.14 Other clinical effects

             9.4.15 Special risks

                    Unknown

        9.5  Others

    10. MANAGEMENT

        10.1 General principles

             Institute life supportive measures.
    
             After skin contact and ingestion immediate decontamination is
             of crucial importance and must be started as soon as
             possible. Skin decontamination with water should be continued
             for at least 15 minutes. Early signs indicating systemic
             poisoning should be looked for (i.e. agitation, malaise,
             vomiting, diarrhoea, CNS-depression, metabolic acidosis).
             Symptomatic therapy is vital (support ventilation and
             circulation, treat cerebral oedema). If signs of systemic
             poisoning appear immediate haemodialysis should be performed.
             Antidote therapy (dichloroacetate - DCA) should also be
             started. Ensure urine flow to prevent kidney damage and
             institute alkalinization of urine if signs of rhabdomyolysis
             occur.

        10.2 Life supportive procedures and symptomatic treatment

             Maintain free airway and assist ventilation when
             needed
    
             Adequate fluid therapy - note the risk of cerebral
             oedema.
    
             Correction of metabolic acidosis (large doses of buffer
             solution may be needed) and electrolyte disturbances
             (hypokalaemia, hypocalcaemia).
    
             Alkalinization of urine to prevent myoglobin precipitation in
             the renal tubule.
    
             Inotropic support (dopamine, dobutamine) in case of
             myocardial insufficiency.
    
             Prevention and treatment of cerebral oedema.
    
             Further symptomatic therapy as needed.

        10.3 Decontamination

             Ingestion
    
             Give water for dilution. Gastric emptying by a thin
             nasogastric tube as soon as possible followed by cautious
             gastric lavage with cold water. After ingestion, gastric

             emptying is recommended in spite of the risk of corrosive
             damage as systemic poisoning of MCA is so severe. Treatment
             of local damage to the gastrointestinal tract as for acids in
             general.
    
             Inhalation
    
             Move the patient to fresh air. If initial symptoms of
             irritant damage such as cough occur, place the patient in
             absolute rest, - if possible in a semi-recumbent position.
             Give supplemental oxygen. Optimal symptomatic treatment
             including broncho-dilators (beta-2-receptor stimulants),
             assisted ventilation etc. Corticosteroid therapy may be
             beneficial for pulmonary manifestations.
    
             Skin exposure
    
             Immediately flush with plenty of water - even under the
             clothes. Remove contaminated clothing, wrist watch etc.
             Flushing with water should be continued for at least 15
             minutes. (At some plants where MCA is produced special
             arrangements have been carried out e.g. bath tubs filled with
             saturated 3-5% sodium bicarbonate solution into which the
             exposed person jumps, or after the initial flushing with
             water exposed areas are covered with dressings soaked with
             sodium bicarbonate solution.)
    
             Decontamination must be started without any delay to prevent
             skin absorption.
    
             If exposed area is >1% of body surface (the palm of the
             hand) immediate transport to hospital (after adequate
             decontamination). It would be prudent to keep victims under
             observation for at least six hours.
    
             Eye exposure
    
             Immediate gentle flushing with water for at least 15 minutes.
             Examination by an ophthalmologist should be carried
             out.

        10.4 Enhanced elimination

             At the slightest sign of systemic poisoning or if large
             areas are exposed (>5 to 10% of body surface) haemodialysis
             should be started. If signs of myoglobinaemia haemodialysis
             should be combined with plasmapheresis.

        10.5 Antidote treatment

             10.5.1 Adults

                    Dichloroacetate (DCA) (as aqueous solution of
                    the sodium salt) should be given if >6% of body
                    surface is exposed to MCA (or ingested): 50 mg/kg body
                    weight intravenously during 10 minutes. This dose is
                    repeated after 2 hours. The dose of DCA should
                    probably be doubled if hemodialysis is performed.
                    

             10.5.2 Children

                    See 10.5.1

        10.6 Management discussion

             Decontamination: After skin exposure immediate
             decontamination is of crucial importance to prevent skin
             absorption. At some plants bicarbonate is used as a
             decontaminating fluid. Bicarbonate is used for neutralization
             of MCA and perhaps also to extract MCA absorbed through the
             skin (Huismanss, Akzo Zout Chemie, Hengelo, Holland).
             Probably instant decontamination (by flushing with water or
             jumping into bicarbonate solution) is the most important
             measure after skin exposure.
    
             After ingestion, gastric emptying is recommended in spite of
             the risk of corrosive damage as systemic poisoning of MCA is
             so severe.
    
             Haemodialysis should be performed as soon as possible at any
             sign of systemic poisoning to eliminate the toxic products
             (MCA and its metabolites) as well as to treat renal failure
             (Kulling et al., 1992).
    
             Plasmapheresis could be added to haemodialysis for
             elimination of myoglobin molecules that are poorly dialysable
             (Kulling et al., 1992).
    
             Antidote treatment: Dichloroacetate can compensate loss of
             activity of pyruvate dehydrogenase and ketoglutarate
             dehydrogenase, but only if not all molecules are inhibited.
             Dichloroacetate acts by inhibiting PHD-kinase, a protein
             which is attached to the pyruvate dehydrogenase complex and
             inactivates PHD by phosphorylation; thus, inhibition of the
             kinase would lead to a greater availability of PHD. Since DCA
             completely abolishes mortality in rodents (see below) if
             administered 15 minutes after MCA intoxication, it seems
             likely that this mechanism is of prime importance.
    

             In rodents DCA was given 15 minutes after MCA intoxication
             (80 mg/kg iv) and survival rate increased from 8% (untreated)
             to 83% (50 mg/kg DCA) and to 100% (100 mg DCA) (Régnier et
             al., 1996).
    
             DCA has been used in clinical studies in the treatment of
             lactic acidosis from several origins (Stacpoole, 1989;
             Stacpoole et al., 1992) and has been quite extensively
             studied (Curry et al., 1985; Curry et al., 1991; Krishna et
             al., 1994; Stacpoole, 1989; Stacpoole et al., 1988; Wells et
             al., 1980). No side effects from this treatment has been
             reported in these studies.
    
             Mortality in severe MCA poisoning is high. DCA seems to be an
             effective antidote in the treatment of MCA poisoning in
             animal models and from clinical trials DCA seems to be safe.
             This treatment should be tried in severe MCA poisoning.
             However, as there are no clinical experience in treating MCA
             poisoning with DCA each case should be carefully monitored
             for the evaluation of this proposed treatment. A protocol for
             this purpose is given below. 
    
             [Earlier recommended therapy (not longer recommended as this
             therapy was based on a hypothesis proven to be wrong).
    
             Ethanol as an acetate donor (oxidation of ethanol to acetate)
             to prevent systemic poisoning (Gosselin et al., 1984).
             Ethanol protects rats and monkeys against monochloro-ethanol
             (Pieterson et al., 1968) and is given as an acetate donor in
             fluoroacetate poisoning (Chenoweth, 1949; Hutchens et al.,
             1949; Pieterson et al., 1968). Ethanol may also block some
             metabolic step(s) preventing formation of toxic metabolites.
             
    
             Monoacetin (glycerol monoacetate) as an acetate donor for
             fluoroacetate poisoning (Chenoweth et al., 1951; Gosselin et
             al., 1984). However, there is no clinical evidence of its
             efficacy. It might even induce sedation, respiratory
             stimulation, vasodilatation, haemolysis, capillary damage
             (Spoerke et al., 1986). While glycerol acetate protects
             animals against the toxicity of MFA (monofluoro acetate)
             similar doses of glycerol monoacetate potentiated the
             toxicity of MCA (Gibson, 1971).

             N-acetylcysteine as a sulfhydryl donor and as a glutathione
             precursor. In animal studies cysteine has proven effective in
             reducing MCA toxicity (Bakhisek, 1978; Kurchatov & Vasileva,
             1976).
    

             The following protocol has been recommended for studies of
             DCA treatment in MCA poisonings.
    
             1.  Adequate documentation of skin damage - drawing on the
                 skin, photo etc.
    
             2.  Monitor haemodynamics at regular intervals (hourly)
                 for 24 hours (or longer)- blood pressure, heart rate,
                 and if possible central venous pressure, pulmonary
                 artery pressure, pulmonary capillary wedge pressure,
                 cardiac output etc.
    
             3.  Blood analyses
    
                                                                              
          Time     Acid/base,    Electrolytes          B-Glucose  S-Creatinine,
                   lactate       (K+, Na+, Cl-)                   S-Urea
                                                                              
          Entry    ×             ×                     ×          ×
    
          1 h      ×
    
          2 h      ×             ×                     ×          ×
    
          3 h      ×
    
          4 h      ×             ×                     ×          ×
    
          5 h      ×
    
          6 h      ×             ×                     ×          ×
    
          7 h      ×
    
          8 h      ×             ×                     ×          ×
    
          12 h     ×             ×                     ×          ×
    
          16 h     ×             ×                     ×          ×
    
          20 h     ×             ×                     ×          ×
    
          24 h     ×             ×                     ×          ×
    
          36 h     ×             ×                     ×          ×
    
          48 h     ×             ×                     ×          ×
    


                                                                            
         Time      S-Creatine       S-AST,          S-Myoglobin       Coagualtion
                   kinase           S-ALT,                            parameters
                                    S-Bilirubin
                                                                           
        Entry      ×                ×               ×                 ×
    
        1 h
    
        2 h
    
        3 h
    
        4 h
    
        5 h
    
        6 h
    
        7 h
    
        8 h        ×                ×               ×                 ×
    
       12 h
    
        16 h       ×                ×               ×                 ×
    
        20 h
    
        24 h       ×                ×               ×                 ×
    
        36 h       ×                ×               ×                 ×
    
        48 h       ×                ×               ×                 ×
    
             4.  Analyses of MCA and DCA concentrations in plasma
                 (EDTA/heparin tubes) minimum 2 mL blood. Separate and
                 freeze the plasma.

    
                 MCA as soon as possible and thereafter after 5, 10,
                 20, 40, 60, 120, 240 minutes and thereafter after
                 another 2 hours, 6 hours, 10 hours and 22 hours
    
                 DCA 5 minutes before administration, at administration
                 and thereafter as for MCA after 5, 10, 20, 40, 60,
                 120, 240 minutes and thereafter after another 2 hours,
                 6 hours, 10 hours and 22 hours.
    
            Time     MCA     *         DCA
    
            Entry                      Not appl.
    
            5 min
    
            10 min
    
            20 min
    
            40 min
    
            1 h
    
            2 h
    
            4 h
    
            6 h
    
            12 h
    
            22 h
    
            44 h
    
            *: tag timepoint immediately prior to administration of DCA:
               determine DCA in this and all subsequent blood samples.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Skin exposure
    
             1. It is quite unclear why systemic intoxication occurs in
             some cases while in many others under seemingly comparable
             circumstances such as body surface, temperature and physical
             state of MCA, first aid etc no systemic symptoms appear (no
             biological data are available in these cases) (Vincent,
             1987).
    

             2. A 25-year-old man who was splashed with monochloroacetic
             acid at 60°C suffered extensive first degree burns of the
             face, neck, upper chest, groins and legs. One hour after the
             accident he developed a cough with bloody sputum, and
             convulsions, became unconscious and died four hours later. At
             autopsy there were signs of alveolar damage and petaechial
             haemorrhages in the pericardium and pleura, and dilatation of
             the right heart (von Oettingen, 1958; Zeldenrust, 1951).
    
             3. Summary of 3 lethal and 1 severe cases (Millischer and
             Ruty, 1986).
    
             a) Two people were exposed to molten MCA over approximately
             10% of their body surface. Immediate showering was probably
             performed. They both died after 11 hours and 18 hours
             respectively. Symptoms in one of the cases were vomiting,
             convulsions, cardiovascular shock, coma and hypokalaemia.
    
             b) A male was exposed to concentrated solution over 5 to 10%
             of his body surface. He immediately showered. Systemic
             symptoms after 1 hour were vomiting, cardiovascular shock,
             hypokalaemia and low urinary output. He recovered without
             specific therapy.
    
             c) A male was exposed to an 80% solution over 15% of his body
             surface. He immediately showered. Systemic poisoning after
             one hour included vomiting, cardiovascular shock,
             convulsions, coma, low urinary output. He died after six
             hours. Autopsy revealed lung and kidney damage.
    
             4. A 47-year-old worker employed in a production plant was
             splashed with molten MCA at 80°C from a drain valve located
             near the ground. He showered immediately and undressed under
             the shower.
    
             Five minutes later in the medical department of the plant, he
             had another shower for 15 minutes. At this time he had first
             degree burns of the front side of both legs estimated at 6%
             of the body surface. The burns were washed and coated with a
             fat cream. His clinical state appeared to be fine and his
             burn pain was bearable. He was taken to his home.
    
             After 3 hours he has experienced  vomiting, diarrhoea,
             alteration of consciousness with alternation of catatonia and
             agitation. His state deteriorates, he becomes delirious and
             is sent to hospital.
    

             After 5 hours post exposure at hospital, he is comatose and 
             goes into cardiovascular shock. A severe metabolic acidosis
             is observed (pH=7.22 after infusion of 500 ml of sodium
             bicarbonate 1.4 g/100 mL), with hypokalaemia (3.1 mmol/l),
             hyperglycaemia (9 mmol/L) and leucocytosis (28,000
             giga/L).
    
             After 7 hours post exposure, second degree cutaneous burns
             (some severe) are estimated at 10% of body area. (CK: at most
             1,500 Ui/L). Symptomatic treatment and metabolic acidosis
             control are difficult (1,250 mL THAM at 3.66 g/100 mL allows
             to correct pH from 7.18 to 7.35 in 3 hours).
    
             After 9 hours post exposure he is treated with ethanol over 2
             days according to the protocol for treatment of methanol
             intoxication.
    
             The outcome is favourable with correction of clinical and
             biological signs within 36 hours. Consciousness is normal at
             the 40th hour. No more complication afterwards (Vincenti,
             1987).
    
             5. A 28-year-old man was splashed with MCA (80% solution). He
             was not wearing any special protective clothing. His clothes
             were removed within a couple of minutes and he was then
             showered with water for 20 minutes. At admission to hospital
             one hour after the accident he had developed 25 to 30% first
             to second degree burns, except for slight disorientation he
             was otherwise unaffected. One hour later his systolic blood
             pressure decreased to 60 mm Hg and he became agitated. Later
             on he became unconscious. ECG showed changes indicative of
             unspecific myocardial damage. Hypokalaemia was prominent the
             first 24 hours (min 2.3 mmol/L 12 hours after the accident).
             He was put on the ventilator and intravenous fluids and high
             doses of inotropic drugs (dopamine, dobutamine) were given.
             His circulation stabilized, but during the first 24 hours
             metabolic acidosis was pronounced (Base Deficit approximately
             10 mOsm/L) in spite of continuous buffer solution
             administration. Antidote therapy with ethanol and
             N-acetylcysteine was given during the first 24 hours. 
    
             Progressive renal failure developed and on the second day he
             became anuric. Treatment with continuous arteriovenous
             haemofiltration and haemofiltration was started. On the
             second day pronounced hypocalcaemia developed. Creatine
             kinase values were very high (max 1800 µkat/L) indicating
             extensive tissue damage and AST max 42 µkat/L, ALT max 11
             µkat/L.
    

             Due to repeated seizure activity on the fourth day
             barbiturates and diazepam were given. On the fifth day he
             also had signs of increased intracranial pressure.
             Hyperventilation was started, but two days later (Day 7) his
             cerebral status deteriorated and he showed signs of cerebral
             herniation. EEG and angiogram verified cerebral death. MCA in
             blood 4, 6, 8 and 12 hours after exposure were 33, 15, 7.8
             and 0.22 mg/L respectively. Autopsy findings indicated that
             kidney damage was to some extent secondary to myoglobin
             precipitation in the renal tubular (Kulling et al.,
             1992).
    
             6. A 24-year-old male worker experienced accidental exposure
             to MCA in molten form (at 58°C) on the skin of both legs. The
             exposure area was estimated as 10% of the victim's skin
             surface. The exposed area was washed with water almost
             continuously from 30 seconds after exposure to 1 hour after
             exposure.
    
             In the first hour following exposure, the victim vomited
             twice and complained of numbness in the left calf, but was
             alert and did not complain of pain. During the second hour,
             the victim had spells of vomiting interspersed with napping
             but responded when spoken to. Three hours following exposure,
             the victim's respiratory rate was 30 and his pulse was 104.
             Heart rate was somewhat irregular, but volume was good.
             During transfer to a hospital, the victim experienced a
             convulsive seizure followed by deep shock. The victim had no
             palpable pulse or blood pressure, an increased respiratory
             rate, and wheezing with some rales. Hemoglobin levels were
             15.9 g, the white blood cell count was 25,200, and hematocrit
             was 46. Blood carbon dioxide, sodium, and chloride levels
             were normal, while potassium levels were low. Glucose and
             saline with 80 mg solu-medrol were administered for 2 hours,
             with a subsequent reduction in dose to 20 mg. Potassium
             chloride was given intravenously, and antihistamines were
             administered intramuscularly. Blood pressure returned to 110,
             but the victim never regained consciousness and died 11 hours
             following the accident.
    
             Autopsy showed congestion, hemorrhage, and confluent petechia
             of the heart, lungs and thymus, congestion of the liver, a
             persistent thymus, and massive bilateral pulmonary congestion
             and edema. Burns on both legs extended to just above the knee
             and were first-degree in nature other than some second-degree
             patches (US-EPA TSCA, 1992).
    

             Ingestion
             A 5-year-old girl was accidentally given 5-6 mL of an 80% MCA
             wart remover (Verzone), from a bottle resembling Triaminicol
             decongestant. Forty five minutes later, she presented to the
             ED in no distress. Initial vital signs were: BP 133/91, P12,
             R 20, T 95.6 and physical examination revealed pale, slightly
             mottled skin, but was otherwise normal. One and one half
             hours post-ingestion, she developed refractory ventricular
             tachycardia, pulmonary oedema, and acidaemia. Despite
             aggressive intervention, the patient died 8 hours
             post-ingestion. An autopsy revealed diffuse gastric erosions,
             fatty liver, and pulmonary and cerebral oedema. A post-mortem
             serum MCA level of 100 mg/L confirmed the ingestion (Feldhaus
             et al., 1993; Rogers, 1995).
    
             Animal case reports
    
             1. A group of 23 heifers (young female cows) were poisoned by
             Na-MCA polluted drinking water. Nine animals died within a
             few hours. Ante-mortem findings were stiffness, unsteady
             gait, later lateral recumbency, exterior paralysis of the
             limbs, tremor and convulsions. One heifer showed signs of
             hyperexcitability and aggressiveness many hours later before
             it collapsed and died within 24 hours. Post-mortems showed
             extreme venous congestion of neck and thorax with petechial
             haemorrhages extending into the muscle layer. Their hearts
             were congested and had multiple endo- and epicardial
             haemorrhages. There were no lesions to the abdominal viscera
             and alimentary tract. Uptake was estimated to be about 170
             mg/kg (Quick et al., 1983).
    
             2. Two ewes and two lambs were found dead near a Na-MCA
             spill. Post mortem findings were similar but also included
             pulmonary congestion and oedema; uptake was estimated to be
             in the range of 39 to 70 mg/kg body weight (Quick et al.,
             1983).
    
             3. Groups of two rabbits were exposed to MCA on 40%, 20%,
             10%, 5%, or 3% of their skin surface area for either 15
             minutes without washing, 1 minute followed by exhaustive
             washing with water, or 1 minute followed by exhaustive
             washing with sodium bicarbonate and application of sodium
             bicarbonate paste. An additional group was exposed on 1% of
             their skin surface for 15 minutes without washing.
    

             Deaths occurred in two to five hours in all 15-minute
             exposure groups except at 1%, and at 40%, 20%, and 10% and
             one animal at 5% for both the water and sodium bicarbonate
             wash groups. Animals showed remarkably few symptoms, but were
             lethargic and comatose before death. Sodium bicarbonate
             treatment did not affect mortality but did appear to lessen
             the severity of skin lesions.
    
             Gross pathological observations included distended peripheral
             venous systems and lack of blood in the right ventricle of
             the heart. The physiological cause of death was not clearly
             determined.
    
             Microscopic examination of the organs had not been completed
             at the time of the report. (US-EPA TSCA, 1992)

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             Protective clothing including protective glasses as for
             acids, should always be used when handling MCA
             solutions.

        12.1 Other

             The antidote DCA was licensed by the Swedish Medical
             Products Agency (August 1999) for use in life threatening
             MCA-exposure. It is available at the Akzo-Nobel plant in
             Skoghall which is the only industry in Sweden that handles
             substantial amounts of MCA.
             The sodium salt of DCA can be dissolved in sterile water and
             subsequently filtered (not heated). The solution is stable
             for at least one year when refrigerated.

    13. REFERENCES

        American Conference of Govermental Industrial Hyienists Inc.
        Documentation of the Threshold Limit Values and Biological
        Exposure Indicies (1986) Cincinnati, Ohio
    
        Andersson H. Akzo Nobel, Skoghall, Sweden, personal communication
        1992.
    
        Bakhisec GV. Cysteine activity in animals poisoned with different
        aliphatic halohydrocarbons. Farmakol Toksikol (Moscow)
        1978;41:342-4.
    
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    14. AUTHOR, REVIEWERS

        Author
        Per Kulling, Swedish Poisons Information Centre, S-171 76
        Stockholm, Sweden
        Phone + 46 8 33 87 65
        Fax   + 46 8 32 75 84
    
        Date 10/86, Updated 8/93, Updated 2/98
    

        Reviewers 
        Jacqueline Jouglard,
        Centre Anti-Poisons,
        Hôpital Salvator, 249,
        Bd Ste-Marguerite,
        13274 Marseille Cédex 9,
        France
        Phone +33 91 75 25 25
    
        Chris Braun,
        Akzo Nobel Nederland bv,
        Postbus 9300, 6800 SB Arnhem.
        The Netherlands
        Phone +31 26 366 44 33
        Fax +31 26 366 32 50
        Date 2/98
    
        Reviewed at INTOX 12, Erfurt, Germany November 2000 
        Reviewers: M. Balali-Mood, B. Groszek, W. Temple, N.
        Langford.
    

See Also:
        Monochloroacetic acid (ICSC)
        Monochloroacetic acid solid (CHEMINFO)
        Monochloroacetic acid solutions (CHEMINFO)