IPCS INCHEM Home

Naphthalene

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 manufacturers, 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. PHYSICOCHEMICAL 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 circumstance of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological halflife 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 INVESTIGATIONS
   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
      9.1.6 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
         9.4.3.1 Central nervous system (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 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      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 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic/specific 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
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    NAPHTHALENE

    International Programme on Chemical Safety
    Poisons Information Monograph 363
    Chemical

    1.  NAME

        1.1  Substance

             Naphthalene

        1.2  Group

             Aromatic

        1.3  Synonyms

             Albocarbon;
             Camphor Tar;
             Dezodorator;
             Mighty 150;
             Mighty RD1;
             Moth Balls;
             Moth flakes;
             Naftalen;
             Naftalen (Polish);
             Naphtalene;
             Naphthalene (ACGIH:DOT:OSHA);
             Naphthalene, Crude Or Refined (UN1334) (DOT);
             Naphthalene, Molten (UN2304) (DOT);
             Naphthalin;
             Naphthaline;
             Naphthene;
             Tar Camphor;
             White tar;

        1.4  Identification numbers

             1.4.1  CAS number

                    91-20-3

             1.4.2  Other numbers

                    RCRA Waste Number: U165
                    UN1334 (DOT)
                    UN2304 (DOT)
                    NCI-C52904;

        1.5  Main brand names, main trade names

        1.6  Main manufacturers, main importers

    2.  SUMMARY

        2.1  Main risks and target organs

             Naphthalene causes haemolysis with subsequent blocking
             of renal tubules by precipitated haemoglobin.  Hepatic
             necrosis can occur.  Haemolysis is more likely to occur in
             individuals with a hereditary deficiency of
             glucose-6-phosphate dehydrogenase, sickle cell anaemia and
             sickle cell trait.

        2.2  Summary of clinical effects

             Skin contact:
    
             Naphthalene causes skin irritation and in the case of a
             sensitized person, severe dermatitis.  Lesions clear
             spontaneously when the exposure is terminated.  Percutaneous
             absorption is apparently inadequate to produce acute systemic
             reactions except in newborns.
    
             Eye contact:
    
             Cataracts and ocular irritation have been produced
             experimentally in rabbits and have been described in man.
    
             Inhalation:
    
             On inhalation naphthalene cases headache, confusion,
             excitement, nausea, vomiting and sweating.  There may be
             dysuria, haematuria and an acute haemolytic reaction.  Rarely
             optic neuritis is encountered.
    
             Ingestion:
    
             After ingestion naphthalene causes abdominal cramps with
             nausea, vomiting and diarrhoea.
    
             Patients may have headache, profuse sweating, listlessness
             and confusion.  In severe poisoning there is coma with or
             without convulsions.
    
             Irritation of the urinary bladder causes urgency, dysuria and
             the passage of a brown or black urine with or without albumin
             and casts.
    
             Acute intravascular haemolysis is the most characteristic
             sign, particularly in persons with red cell
             glucose-6-phosphate dehydrogenase deficiency; it is
             accompanied by anaemia, leucocytosis, fever, haemoglobinuria,
             jaundice, renal insufficiency and sometimes disturbances in
             liver function.
    

             In the absence of adequate supportive treatment, death may
             result from acute renal failure in adults or kernicterus in
             young infants.

        2.3  Diagnosis

             Diagnosis of naphthalene poisoning by ingestion is made
             from the history of exposure and the presence of
             gastrointestinal manifestations and signs and symptoms of
             haemolysis.  Laboratory investigations may show anaemia,
             methaemoglobinaemia and elevated serum bilirubin
             levels.

        2.4  First aid measures and management principles

             If poisoning is due to skin or eye contact remove the
             source of contamination and flush contaminated area with
             lukewarm gently running water for at least 20 minutes. 
             Obtain medical advice immediately.  If inhaled, remove the
             source of contamination and move the patient away from the
             source.  Obtain medical advice immediately.
    
             If recent ingestion of a significant amount is suspected and
             if no convulsion are present consider gastric lavage.  Give
             activated charcoal.
    
             Milk of fatty meals should be avoided for the next 2 to 3
             hours because they may promote absorption.

    3.  PHYSICOCHEMICAL PROPERTIES

        3.1  Origin of the substance

             Naphthalene occurs in coal tar in large quantities and
             is easily isolated from this source in pure condition. It
             also occurs naturally in the essential oils of the roots of
             Radix and Herba ononidis. 
    
             It is prepared from that part of coal tar, which is distilled
             in the 170 to 230C temperature range and is called carbolic
             oil.  The oil is treated with a sodium hydroxide solution (to
             remove phenols) and then distilled, the distillate consisting
             chiefly of naphthalene, and solidifies almost completely.  It
             is pressed and washed with an acid and with a sodium
             hydroxide solution and the final purification of the
             naphthalene is effected by steam distillation or sublimation
             (Pavlov and Terentgev n.d.; Kipping and Kipping, 1941).
    
             Naphthalene may be obtained synthetically by passing the
             vapour of phenylbutylene C6H5CH2CH2CH: CH2 (or of phenyl
             butylene dibromide, C6H5CH2CH2CHBrCH2Br) over red-hot
             lime.  The change involves the loss of hydrogen (Kipping &
             Kipping, 1941).

        3.2  Chemical structure

             Molecular formula: C10H8
    
             Molecular weight: 128.16

        3.3  Physical properties

             3.3.1  Colour

                    White or colourless

             3.3.2  State/Form

                    Solid-crystals

             3.3.3  Description

                    Transparent prismatic plates also available as
                    white scales, powder balls or cakes with a
                    characteristic odour and aromatic taste.  It
                    volatilizes and sublimes at room temperature above the
                    melting point with a characteristic moth ball or
                    strong coal tar odour.  Naphthalene absorbs
                    ultraviolet rays (Windholz, 1983; Reynolds, 1996).
    
                    Boiling point :         217.9C
                    Melting point :         80.2C
                    Flash point  -  open cup 79C
                                    closed cup 88C
                    Autoignition temp: 567C
                    Vapour pressure (at 25C): 0.087 torr
                    Solubility in water, alcohol and ether -
                    Solubility in water:  3mg/100mL at room temperature.
                    Solubility in methanol/ethanol:  7.7g/100mL 
                    Very soluble in ether.
                    pH - no data available.

        3.4  Hazardous characteristics

             This compound in a petroleum ether solution will give
             off purple fluorescence under a mercury light.

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Manufacture of phthalic and anthranilic acids
                    (which are used in making indigo, indanthrene and

                    triphenyl methane dyes), synthetic resins, lubricant,
                    celluloid, lampblack, smokeless powder,
                    hydronaphthalenes (tetralin, decalin).
    
                    Naphthalene is also used in dusting powders, lavatory
                    deodorant discs, wood preservatives, fungicide,
                    mothballs and as an insecticide.  It has been used as
                    an intestinal antiseptic, vermicide and in the
                    treatment of pediculosis and scabies.
    
                    A case of mothball abuse predominantly by inhalation
                    has been described (Weintraub et al., 2000).

        4.2  High risk circumstance of poisoning

             Naphthalene poisoning has occurred mostly in children
             who suck or chew mothballs (Hayes, 1982; Chun et al., 1998;
             Santucci & Shah, 2000).
    
             With the exception of dermatitis due to hypersensitivity with
             positive patch tests, reports of naphthalene poisoning in
             industry are rare (Gosselin et al., 1984).
    
             Individuals with  Glucose-6-phosphate deficiency may be
             susceptible to haemolytic anaemia induced by naphthalene.
             Similar individuals with diseases of the blood, liver and
             kidneys are more prone to adverse effects. Newborn infants
             have increased susceptibility to the haemolytic effects.
             Persons with existing skin disorders may have increased
             absorption.

        4.3  Occupationally exposed populations

             Occupational exposure can occur in the dye industry and
             other chemical synthetic industries.

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Poisoning may occur after ingestion of large doses of
             naphthalene (Windholz, 1983). Ingestion of
             naphtalene-containing mothballs is a common occurrence in
             children.

        5.2  Inhalation

             Naphthalene toxicity can occur by vapour inhalation
             (Gosselin et al., 1984).
    
             Naphtalene and paradichlorobenzene-containing mothballs are
             reported to be abused by inhalation (Weintraub et al.,
             2000).

        5.3  Dermal

             Erythema and dermatitis are hypersensitivity reactions.
             Systemic reactions, such as jaundice and haemolysis have
             occurred after dressing infants in clothing stored with
             naphthalene moth balls suggesting that percutaneous
             absorption may occur (Schafer, 1951; Valaes et al., 1963;
             Gosselin et al., 1984).

        5.4  Eye

             Toxicity has occurred from both vapour contact and from
             systemic adsorption. Common effects are irritation, lens
             opacities and optic neuritis. (Gosselin et al., 1984).

        5.5  Parenteral

             No data available.

        5.6  Other

             Effects of toxicity can be observed in the newborn
             following transplacental transfer of naphthalene or its
             oxidation products (Anziulewicz et al., 1959).

    6.  KINETICS

        6.1  Absorption by route of exposure

             Naphthalene is erratically absorbed when ingested. It is
             rapidly absorbed when inhaled. Dermal absorption in humans,
             especially in infants maybe significant and further enhanced
             by prior application of oils (Hayes, 1982).

        6.2  Distribution by route of exposure

             Effects of toxicity can be observed in the newborn
             following transplacental transfer of naphthalene or its
             oxidation products. 

        6.3  Biological halflife by route of exposure

             No data available.

        6.4  Metabolism

             Naphthalene is metabolized in the liver to yield a
             variety of hydroxy and methylthio derivatives.  In these two
             groups of metabolites alpha-naphthol and 1-methylthio
             naphthalene are the most prominent urinary constituents.  The
             initial metabolite is apparently a 1,2-epoxide produced in
             the liver by mixed function oxidase enzymes.  This reactive
             compound is subsequently converted to naphthalene dihydrodiol

             and to alphanaphthol.  Both compounds are excreted as such
             and as glucuronide conjugates.
    
             Naphthalene dihydrodiol may be further converted in the eye
             to yield 1,2-naphthoquinone, a known cataractogenic agent
             (Gosselin et al., 1984).

        6.5  Elimination and excretion

             Naphthalene dihydrodiol and 2 naphthol are excreted as
             glucuronides in the urine (Gosselin et al., 1984). Conjugates
             of glutathione and cysteine are excreted in the bile (Parke,
             1968).

    7.  TOXICOLOGY

        7.1  Mode of action

             Ingestion of naphthalene results in the formation of an
             epoxide metabolite that is probably responsible for
             haemolysis. (Haddon et al 1998).  Haemolysis mostly occurs in
             individuals with a hereditary deficiency of
             glucose-6-phosphate dehydrogenase due to instability of
             erythrocyte glutathion.  Hepatic necrosis can occur. Ocular
             toxicity can occur due to oxidative stress/lipid peroxidation
             with the thio groups of lens protein. Toxicity may be
             increased in the newborn due to the inability of the newborn
             to conjugate both naphthalene and bilirubin leading to
             kernicterus. Animal studies have reported depletion of
             pulmonary glutathione and dose-dependent bronchiolar
             epithelial cell necrosis, (Richieri  et al., 1988).

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             Toxic effects vary from individual
                             to individual (Gosselin et al., 1984).  For
                             example, ingestion of 6 grams has led to
                             significant toxicity or no symptoms at all
                             (Gidron and Leurer, 1956).
    
                             The mean lethal dose in nonsensitive adults
                             may lie between 5 and 15g (Gosselin et al.,
                             1984).
    
                             Naphthalene is toxic in normal individuals
                             without recognized red cell defects,
                             primarily G6PD deficiency.  It is difficult
                             however, to estimate the lethal dose in
                             non-sensitive individuals because the red

                             cell abnormality has not been excluded
                             convincingly in most reported cases.  In the
                             population, a wide range of susceptible
                             individuals exists, and among sensitive
                             individuals minute doses have induced
                             dangerous reactions (Gosselin et al., 1984;
                             Chun et al., 1998).
    
                             Although naphthalene has no haemolytic
                             properties, its oxidative metabolite
                             alpha-naphthol possesses potent haemolytic
                             activity (Mackell et al., 1951).

                    7.2.1.2  Children

                             A reported dose of two grams in a
                             child has been fatal. This chemical is most
                             dangerous in children, in whom absorption
                             occurs rapidly (Dreisbach and Robertson,
                             1987).
    
                             Newborns are unable to conjugate naphthalene
                             metabolites effectively.  Therefore, they are
                             more susceptible to haemolysis (Vales et al.,
                             1963;  Zuelzer and Apt, 1949).  Their thinner
                             skin and application of baby oil help dermal
                             absorption of lipophilic naphthalene (Dawson
                             et al., 1958).
    
                             2g over a 2 day period killed a 6 year old
                             child.  The clinical features appear to be
                             essentially the same in sensitive and
                             nonsensitive victims.  Haemolytic episodes
                             have been reported in infants with normal red
                             cell glucose-6-phosphate dehydrogenase
                             activity and normal glutathione stability
                             (Gosselin et al., 1984; Chun et al., 1998;
                             Santucci & Shah, 2000).

             7.2.2  Relevant animal data

                    The oral LD50 values for naphthalene in rats is
                    between 1760mg/kg and 2,400mg/kg.  The corresponding
                    dermal values are both greater than 2,500 mg/kg.
    
                    Acute haemolytic anaemia was produced in dogs by
                    dosages of 411 mg/kg or greater.  Heinz bodies
                    appeared in the circulating red cells before
                    haemolysis was evident.  Plasma, collected 2 days
                    after ingestion of naphthalene produced Heinz bodies
                    in normal dog erythrocytes incubated for one hour.
    

                    In rabbits, eye lesions (cataract, retinal lesions,
                    intraocular crystalline deposits, disturbances of the
                    ciliary body, and general metabolic changes) have been
                    reproduced experimentally by naphthalene (1500
                    mg/rabbit/day) (Hayes, 1982).
    
                    Parenteral administration of naphthalene has caused
                    acute injury to clara cells in the respiratory tracts
                    of mice, hamsters, and other animal species (Plopper
                    at al., 1992).

             7.2.3  Relevant in vitro data

                    No data available.

             7.2.4  Workplace standards

                    Threshold limit value - Time weighted average:  10 ppm
    
                    Threshold limit value - STEL: 15 ppm (American
                    Conference of Government Industrial Hygienists
                    ACGH)

             7.2.5  Acceptable daily intake (ADI)

                    No data available.

        7.3  Carcinogenicity

             Naphthalene and coal tar exposure have been associated
             with laryngeal and intestinal carcinoma (Wolf 1976).

        7.4  Teratogenicity

             Naphthalene induced cataracts in rats when used as an
             antiseptic (Zhikov  et al., 1965).

        7.5  Mutagenicity

             No data available.

        7.6  Interactions

             No data available.

    8.  TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        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
                             "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

             Sample collection
    
             Collect blood to determine the haemoglobin content,
             reticulocyte count, methaemoglobin level, blood gases, blood
             group and to study the blood picture.  Collect serum to
             determine the bilirubin level.
    
             Biomedical analysis
    
             Haematological findings may include a rapid fall in
             erythrocyte count, haemoglobin concentration and haematocrit
             followed by a temporary increase in reticulocytes and
             normoblasta in the peripheral blood.  During a haemolytic
             crisis the fragility of the remaining cells is increased. 
             Haemoglobin is present in the plasma.  Red cells may contain
             Heinz bodies and the cells may be fragmented showing
             anisocytosis and poikilocytosis.
    

             Serum bilirubin is elevated
    
             The urine may be wine coloured brown or black.  The colour
             may vary from patient to patient or in the same patient
             during the course of illness.
    
             In most but not all persons with naphthalene induced
             haemolysis, a deficiency of G6PD can be demonstrated (Hayes,
             1982).
    
             Toxicological analysis
    
             The most important metabolite of naphthalene in human urine
             is alpha-naphtol.  Beta-naphthol and alpha- and
             beta-naphtholquinone occur in small concentrations.

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Headache, abdominal pain, nausea, vomiting,
                    diarrhoea, fever and profuse sweating are the early
                    features of poisoning, following ingestion.
    
                    Patients may develop optic neuritis, haemolytic
                    anaemia and have jaundice, pallor and hepatic
                    necrosis.  Patients with G6PD deficiency, sickle cell
                    anaemia, or sickle trait are more susceptible to
                    haemolysis and methaemaglobulinaemia.
    
                    There may be haematuria, haemoglobinuria and dysuria,
                    progressing to oliguria or anuria.
    
                    Methaemoglobinaemia and cyanosis can occur.
    
                    In severe poisoning, excitement, coma and convulsions
                    can occur (Dreisbach & Robertson, 1987; Reynolds,
                    1996; Windholz, 1983).

             9.1.2  Inhalation

                    Headache, mental confusion, and visual
                    disturbances have been reported from exposure to
                    naphthalene vapour (Dreisbach & Robertson, 1987).
                    Prolonged inhalation produces nausea, vomiting and
                    disorientation.  Delayed acute intravascular
                    haemolysis in sensitive persons is characteristic
                    (Gosselin et al., 1984). Respiratory failure and
                    pulmonary oedema have also been reported.

             9.1.3  Skin exposure

                    Naphthelene causes skin irritation and in the
                    case of a sensitized person, severe dermatitis.
                    Systemic reactions, such as jaundice and haemolysis
                    have occurred after dressing infants in clothing
                    stored with naphthalene moth balls suggesting that
                    percutaneous absorption may occur (Schafer, 1951;
                    Valaes et al., 1963; Gosselin et al., 1984). Newborn
                    infants may develop kernicterus from exposure to
                    heavily treated clothing (Hayes, 1982).

             9.1.4  Eye contact

                    Eye contact causes corneal irritation and
                    injury (Dreisbach & Robertson, 1987).

             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

                    Chronic abuse of mothballs containing
                    naphtalene and   paradichlorobenzene was reported to
                    cause peripheral neuropathy and chronic renal failure
                    (Weintraub et al., 2000). Chronic sniffing of
                    naphthalene containing mothballs can cause liver
                    necrosis (Siegal and Wason, 1986).

             9.2.3  Skin exposure

                    Continuous handling of naphthalene may produce
                    a dermatitis characterized by itching, redness,
                    scaling, weeping and crusting of the skin (Dreisbach &
                    Robertson, 1987).

             9.2.4  Eye contact

                    Cataracts may form following chronic exposure
                    (Gosselin, 1984).

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             Most naphthalene poisonings have occurred in children. 
             The condition is characterized by haemolytic anaemia, but
             nonspecific symptoms (headache, anorexia, vomiting, diarrhoea
             and other gastrointestinal disturbances) generally appear
             before there is any objective evidence of haemolysis.
    
             Rapid progression to coma and convulsions indicates poor
             prognosis. Anuria may persist for 1 to 2 weeks with eventual
             complete recovery.  Dermal effects disappear 1 to 6 months
             after discontinuing exposure (Dreisbach & Robertson,
             1987).
    
             In the absence of adequate supportive treatment, death may
             result from acute renal failure in adults or kernicterus in
             young infants (Gosselin et al., 1984).

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    There may be tachycardia and in severe cases
                    arrhythmia secondary to hyperkalaemia (Kurz, 1984) and
                    circulatory failure (Kouri et al., 1993).

             9.4.2  Respiratory

                    Respitarory distress, respiratory failure and
                    pulmonary oedema have been reported infrequently
                    (Kouri et al., 1993).

             9.4.3  Neurological

                    9.4.3.1  Central nervous system (CNS)

                             There may be lethargy, headache,
                             irritability, restlessness, ataxia, delirium,
                             convulsions and coma (Gidron and Leurer,
                             1956; Kouri, 1993).

                    9.4.3.2  Peripheral nervous system

                             No data available

                    9.4.3.3  Autonomic nervous system

                             No data available

                    9.4.3.4  Skeletal and smooth muscle

                             No data available

             9.4.4  Gastrointestinal

                    Nausea, vomiting and diarrhoea can be delayed
                    up to 48 hours (Gidron and Leurer, 1956). Nausea may
                    also occur after inhalation.

             9.4.5  Hepatic

                    Jaundice, hepatomegaly and centrilobular
                    necrosis of the liver may be observed rarely (Dawson
                    et al., 1958; Siegaland Wason, 1986).

             9.4.6  Urinary

                    9.4.6.1  Renal

                             There may be haemoglobinuria,
                             oliguria and renal failure (secondary to
                             acute tubular necrosis after haemolysis)
                             (Hayes, 1982). The urine may be dark brown,
                             red, or pink when significant haemolysis
                             occurs (Ostlere et al., 1988)

                    9.4.6.2  Other

                             There may be dysuria, urgency and
                             haematuria due to irritation of the lower
                             urinary tract.

             9.4.7  Endocrine and reproductive systems

                    No data available.

             9.4.8  Dermatological

                    Liquid vapour and dust are irritating to the
                    skin causing erythema and dermatitis (Gosselin et al.,
                    1984). Exfoilative contact dermatitis has been
                    reported (Fanbergh,1940)

             9.4.9  Eye, ear, nose, throat: local effects

                    Corneal ulceration and cataracts following
                    exposure to naphthalene vapour and dust can be

                    demostrated experimentally and occur occasionally in
                    man (Gosselin et al., 1984).
    
                    After ingestion of 5 g of naphthalene over 13 hours a
                    man developed cataract (Lezenius, 1902).
    
                    Workers exposed to high levels of naphthalene fumes
                    have developed lens opacity (Dreisbach & Robertson,
                    1987).
    
                    It is thought that the cataractogenic effects of
                    naphthalene following ingestion is due to the
                    metabolites 1,2-dihydroxynaphthalene and
                    1,2-naphthaquinone (Pirie, 1968).

             9.4.10 Haematological

                    Naphthalene is known to trigger haemolytic
                    crises in sensitive individuals who are believed to
                    possess a genetically determined metabolic defect
                    which is X-linked, resulting in deficiency of glucose
                    6 phosphate dehydrogenase activity in red blood cells.
                    They are unable to maintain a balance between red
                    blood cells stores of oxidized and reduced
                    glutathione.
    
                    There is fragmentation of red cells with anisocytosis
                    and poikilocytosis, severe anaemia with nucleated red
                    cells, leucocytosis and dramatic decreases in
                    haemoglobin concentrations, haematocrit and red cell
                    count.  More severe reactions also include Heinz body
                    formation, haemoglobinuria and mild
                    methaemoglobinaemia.  The haemolytic episode tend to
                    be self limiting (Shannon & Buchanan, 1982; Zuelzer &
                    Apt, 1949).  Damage occurs most intensively in older
                    cells, i.e. those approaching the normal life span of
                    100 to 120 days.
    
                    Patients develop jaundice and the chief threat to life
                    in young infants is kernicterus that carries a high
                    mortality.
    
                    In older children and adults the haemolytic crisis may
                    be followed by acute renal failure.

             9.4.11 Immunological

                    No data available.

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Metabolic acidosis may develop due
                             to acute renal failure.

                    9.4.12.2 Fluid and electrolyte disturbances

                             May cause acute renal failure and
                             hyperkalaemia, due to haemolysis.

                    9.4.12.3 Others

                             No data available.

             9.4.13 Allergic reactions

                    A chronic scaling dermatitis which gradually
                    cleared each time the patient was hospitalized but
                    recurred within a day or two each time he returned
                    home was attributed to naphthalene after a direct test
                    indicated susceptibility.  He carefully avoided
                    naphthalene and had no recurrence for 7 years when a
                    report of the case was published (Hayes, 1982). 
                    Erythema and exfoliative contact dermatitis have also
                    been reported (Gosselin et al., 1984).

             9.4.14 Other clinical effects

                    There may be fever.

             9.4.15 Special risks

                    Pregnancy
                    Transplacental transfer of naphthalene or its
                    oxidation products can occur.  In two instances where
                    young women developed the habit of sucking moth balls
                    during the last trimester of pregnancy, haemolytic
                    anaemia was discovered in one of them a few days
                    before delivery.  In the other haemolytic anaemia was
                    detected later when her infant developed jaundice.  No
                    abnormality was noted in the babies at birth but
                    jaundice was noted in one after 7 hours and in the
                    other on the 3rd day.  The mothers and babies
                    recovered (Anziulewicz et al., 1959; Hayes, 1982).
    
                    Enzyme deficiency
                    Patients with G6PD deficiency, sickle cell anaemia and
                    sickle cell trait are at high risk of developing acute
                    haemolysis after exposure to naphthalene.

        9.5  Other

             No data available.

        9.6  Summary


    10. MANAGEMENT

        10.1 General principles

             Skin contact
             Flush contaminated area with lukewarm gently running water
             for at least 20 minutes (Gosselin et al., 1984).
    
             Eye contact
             Flush with lukewarm gently running water for at least 20
             minutes (Gosselin et al., 1984).
    
             Inhalation
             If acute symptoms are present remove source of contamination
             and/or move victim away from the source.
             Make a proper assessment of airway, breathing and
             circulation. Administer oxygen if patient cyanosed. Perform
             cardio-pulmonary resusitation if appropriate. Support
             ventilation using appropriate mechanical device. 
    
             Ingestion
             If a significant amount is ingested and if no convulsions
             present cautious gastric lavage can be considered. Lavage is
             not likely to be effective if more than 2 hours have passed
             since ingestion (Siegal &  Wason, 1986).
    
             Give activated charcoal 1 gram per kilogram up to 50 grams as
             a slurry in water.
    
             Milk or fatty meals should be avoided for the following 2 to
             3 hours because they may promote absorption (Gosselin et al.,
             1984; Siegal and Wason, 1986).

        10.2 Life supportive procedures and symptomatic/specific treatment

             A severe anaemia due to haemolysis may require small
             repeated blood transfusions preferably with red cells from a
             non-sensitive individual.  Give repeated small blood
             transfusions until the haemoglobin concentration is 60 to 80%
             of normal.  Corticosteroids appear to have been beneficial in
             a few cases of naphthalene haemolysis (Hayes, 1982; Dreisbach
             & Robertson, 1987).
    

             For kernicterus haemodialysis and exchange transfusion may be
             required (Hayes, 1982; Dreisbach & Robertson, 1987).
    
             Control convulsions with diazepam 5 to 10mg intravenous (IV)
             slowly (paediatric dose 0.2mg/kg).  Repeat if necessary.
    
             Give sodium bicarbonate 5g orally every 4 hours or as
             necessary to maintain alkaline urine.  Give fluids up to 15
             mL/kg/h with furosemide 1mg/kg to produce maximum diuresis
             and reduce injury to the kidney from haemoglobin products
             (Dreisbach & Robertson, 1987).
    
             Check renal function regularly.  Anticipate and treat renal
             failure.
    
             If methaemaglobulin levels are greater than 30% treatment may
             be required.

        10.3 Decontamination

             Skin contact
             Flush contaminated area with lukewarm gently running water
             for at least 20 minutes.
    
             Eye contact
             Flush with lukewarm gently running water for at least 20
             minutes.
    
             Inhalation
             If acute symptoms are present remove source of contamination
             and/or move victim away from the source.
    
             Ingestion
             If a significant amount is ingested and if no convulsions
             cautious gastric lavage can be considered. Lavage is not
             likely to be effective if more than 2 hours have passed since
             ingestion (Siegal and Wason, 1986).
    
             Give activated charcoal 1 gram per kilogram up to 50 grams as
             a slurry in water.
    
             Milk or fatty meals should be avoided for the following 2 to
             3 hours because they may promote absorption (Gosselin et al.,
             1984; Siegal and Wason, 1986).

        10.4 Enhanced elimination

             In the event of intravascular haemolysis with
             haemoglobinuria, protect the kidneys by promoting a brisk
             flow or dilute urine; an osmotic diuretic such as mannitol is
             often used for this purpose (Gosselin et al., 1984).
    

             Haemodialysis should be used in the presence of severe
             central nervous system symptoms such as kernicterus (Gosselin
             et al., 1984; Dreisbach & Robertson, 1987).

        10.5 Antidote treatment

             10.5.1 Adults

                    No data available

             10.5.2 Children

                    No data available

        10.6 Management discussion

             A patient who had ingested naphthalene with suicidal
             intent and who was treated promptly with 100mg of cortisone
             daily developed Heinz bodies and excreted naphthalene
             derivatives but did not become ill.  The value of cortisone
             in naphthalene poisoning remains to be confirmed (Hayes,
             1982).
    
             Alkalinization of urine may be helpful by giving small
             amounts of sodium bicarbonate but many investigators doubt
             the efficacy of this measure in preventing blockade of renal
             tubules (Gosselin et al., 1984).
    
             Empiric treatment of methemoglobinemia with methylene blue is
             contraindicated in patients with G6PD deficiency (Chun et
             al., 1998).

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Acute haemolysis following naphthalene inhalation
             occurred in 21 infants.  Eight developed kernicterus and 2
             died. G6PD activity was normal in 9 infants (Valaes et al.,
             1963).
    
             Acute haemolytic anaemia due to naphthalene poisoning
             occurred in a newborn following skin absorption from diapers
             stored in naphthalene moth balls (Schafer, 1951).

    12. Additional information

        12.1 Specific preventive measures

             No information available.

        12.2 Other

             No information available.

    13. REFERENCES

        American Conference of Governmental Industrial Hygienists
        Inc.  Documentation of the Threshold Limit Values and Biological
        Exposure Indices (1986)  Cincinnati, Ohio, p.420.
    
        Anziulewicz JA, Herman JD and Chiarulli EE (1959)  Transplacental
        naphthalene poisoning.  American Journal of Obstetrics and
        Gynaecology, 78:519-521.
    
        Chun T, Perrone J, Osterhoudt K, Ugur S, Henretig F (1998)
        Mothball blues: confusion in naphtalene toxicities and treatment.
        Clin Toxicol, 36: 465 (abstract)
    
        Dawson JP, Thayer WW, Desfoges JF (1958)  Acute haemolytic anaemia
        in the newborn infant due to napthalene poisoning.  Blood,
        13:1113-1125.
    
        Dreisbach RH and Robertson WO (1987)  Handbook of Poisoning: 
        Prevention, Diagnosis and Treatment.  Los Altos California,
        Appleton and Lange, pp 194-195.
    
        Fanbergh SJ. Exfoilative dermatitis due to naphthalene. Arch Derm
        Syph 1940;43:53-56 
    
        Gidron E and Leurer J (1956)  Naphthalene poisoning.  Lancet,
        1:228-230.
    
        Gosselin RE, Smith RP, Hodge HC (1984) ed. Clinical Toxicology of
        Commercial Products, Baltimore, Williams and Wilkins pp. II-153,
        III-307 - III - 310.
    
        Hayes WJ (1982) ed.  Pesticides studies in man, Baltimore,
        Williams and Wilkins pp. 136-137. 
    
        Haddad LM, Shannon MW, Winchester JF. Clinical Management of
        Poisoning and Drug Overdose. 3rd Edition WB Saunders Company
    
        Kipping FS and Kipping FB (1941) ed.  Perkin and Kipping's organic
        chemistry part II, London and Edinburgh, W and R Chambers Ltd.
        pp 475 - 480.
    
        Kouri N, Valti H, Papazoglou K et al. Severe haemolysis with
        metabolic disturbances after naphthalene poisoning. (Abstract)
        Presented at the EAPCCT Animal Scientific Meeting Birmingham UK.
        May 1993.
    

        Kurz JM. Naphthalene poisoning: critical care nursing techniques.
        Dimensions Crit Care Nurs 1987;6:264-270
    
        Lezenius A (1902)  A case of naphthalene cataract in a human
        being.   Klin Monatsbl Augenheilkd, 40:129-140 (in German).
    
        Mackell JV; Rieders R, Brieger H & Bauer EL (1951)  Acute
        haemolytic anaemia due to ingestion of naphthalene mothballs. 
        Pediatrics 7:722-728.
    
        Morrison RH and Boyd RN (1978)  ed.  Organic chemistry, New Delhi,
        Prentice Hall of India Private Ltd., pp. 968-970.
    
        Ostlere L, Amos R, Wass JAH. Haemoltic anaemia associated with
        indigestion of naphthalene-containing anointing oil. Postgrad Med
        J 1988;64:444-446
    
        Pavlov B and Terentger A (n.d.)  Organic chemistry, Moscow,
        Foreign Languages Publishing House.  pp 499.
    
        Parke DV. The biochemistry of foreign compounds. Pergamon Press,
        Oxford, UK 1968.
    
        Plopper CG, Suverkropp C, Morin D et al. Relationship of
        cytochrome p450 activity to clara cell cytotoxicity. I.
        Histopathologic comparision of the respiratory tract of mice,
        rats, and hamsters after parenteral administration of naphthalene.
        J. Pharmacol Exp Ther 1992;261:353-363
    
        Pirie A (1968)  Pathology in the eye of naphthalene-fed rabbit.  
        Exp Eye Res, 7:354-357.
    
        Reynolds JEF (1996) 31 ed.  Martindale The Extra Pharmacopoeia,
        London, The pharmaceutical Press.
    
        Richieri PR, Buckpitt AR. Glutathione depletion by naphthalene in
        isolated hepatocytes and by naphthalene oside in vivo. Biochem
        Pharmacol 1988;37:2473-2478.
    
        Santucci K & Shah B (2000) Association of naphtalene with acute
        hemolytic anemia. Acad Emerg Med, 7: 42-47
    
        Schafer WB (1951)  Acute haemolytic anaemia related to
        naphthalene. Report of a case in a newborn infant.  Pediatrics,
        7:172-174.
    
        Shannon K and Buchanan GR (1982)  Severe haemolytic anaemia in
        black children with glucose 6-phoshate dehydrogenase deficiency. 
        Pediatrics, 70:364-369.
    

        Siegel E and Wason (1986)  Mothball toxicity.  In the Pediatric
        Clinics of North America, Ed:  Blumer, J.L. and Reed M.D.,
        33:369-374.
    
        Valaes T, Doxiadis SA, and Fessas P (1963)  Acute haemolysis due
        to naphthalene inhalation.  Journal of Pediatrics, 
        63:904-915.
    
        Weintraub E, Gandhi D, Robinson C (2000) Medical complications due
        to mothball abuse. South Med J, 93: 427-429
    
        Windholz M ed. (1983) 10 ED The Merck Index:  an encyclopaedia of
        chemicals, drugs and biologicals, Rahway, New Jersey Merck and
        Co., Inc.
    
        Wolf O. Deutche Gesundheitwesen 1976;31:996
    
        Zhikov E, Atanasov L. Experiments in obtaining and preventing
        congential cataracts in rats. Opthalmolgia 1965;2:105-112.
    
        Zuelzer WW, and Apt L (1949)  Acute haemolytic anaemia due to
        naphthalene poisoning  A clinical and experimental study.  Journal
        of American Medical Association,141:185-190.

    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
        ADDRESS(ES)

        Authors(s): Dr Ravindra Fernando
                    National Poisons Information Centre
                    Faculty of Medicine
                    Kynsey Road
                    Colombo 8
                    Sri Lanka
    
                    Miss Shiromini Nissanka
                    (as above)
    
        Date:       January 1992
    
        Update:     September 2000, MO Rambourg Schepens
    
        Peer Reviewed
        INTOX 12 Meeting, Erfurt, Germany, November 9, 2000 
        Reviewers: M. Balali-Mood, W. Temple, B. Groszek, N.
        Langford.
    



    See Also:
       Toxicological Abbreviations
       Naphthalene (ICSC)
       Naphthalene (IARC Summary & Evaluation, Volume 82, 2002)