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 230°C 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 : 217.9°C
Melting point : 80.2°C
Flash point - open cup 79°C
closed cup 88°C
Autoignition temp: 567°C
Vapour pressure (at 25°C): 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
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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.