Naphthalene - Aromatic Hydrocarbons

Naphthalene

Synonyms

·              Moth flake, Tar camphor, White tar.

Physical Appearance

·              White scaly powder which volatilises at room temperature.

Sources

·              Naphthalene occurs naturally in the essential oils of the roots of Radix and Herba ononidis, and crude oil.

·              It can be manufactured by crystallising and separating the naphthalene fraction.

·              Naphthalene can also be produced by boiling coal tar oils at temperatures between 200–2500 C, followed by crystal- lisation and distillation.

·              It can also be derived from catalytic processing of petro-leum, or isolated from cracked petroleum.

·              Naphthalene is formed in cigarette smoke by pyrolysis, and is also a photodecomposition product of carbaryl, an agricultural pesticide.

Uses

·              Moth repellent (in the form of moth balls) (Fig 27.2)*

·              Deodorant cakes

·              Scintillation counters.

Toxicokinetics and Mode of Action

Naphthalene itself is not responsible for the toxic effects. Its metabolites alpha and beta naphthol as well as naphtho-quinone are powerful haemolytic agents. Individuals with glucose-6-phosphate dehydrogenase (G- 6-PD) deficiency are especially vulnerable to the toxicity of these metabolites. Naphthalene is first metabolised by hepatic mixed func-tion oxidases to the epoxide, naphthalene-1,2-oxide. The epoxide is enzymatically converted into the dihydrodiol, 1, 2-dihydroxy- 1,2-dihydronaphthalene or conjugated with glutathione. The dihydrodiol is then conjugated to form a polar compound with glucuronic acid or sulfate, or further dehy-drogenated to form highly reactive 1,2-dihydroxynaphthalene. Dihydroxynaphthalene can be enzymatically conjugated with sulfate or glucuronic acid or spontaneously oxidised to form 1,2-naphthoquinone. Naphthalene is also metabolised to mercapturic acid derivatives.

Naphthalene metabolites (naphthols and naphthylglycuro-nates) are excreted in the urine as 1-naphthylmercapturic acid (15% of absorbed dose), as conjugates of 1,2-dihydronaphtha-lene-1,2-diol (10% of absorbed dose), and as 1- and 2-naphthols and 1,2-dihydroxynaphthalene. Conjugates of glutathione (cysteinylglycine, and cysteine; intermediates in formation of mercapturic acids) are excreted mainly in the bile as metabolites of naphthalene.

Naphthalene can be absorbed via oral, inhalation, and dermal routes.

Clinical Features

·      Non-haemolytic manifestations: Vomiting, abdominal pain,diarrhoea, headache, diaphoresis, optic neuritis, restlessness, lethargy, fever, convulsions, hepatomegaly, splenomegaly. Hyperbilirubinaemia and fatal kernicterus may occur in newborns with significant haemolysis. Centrilobular necrosis occurred in one paediatric poisoning case. Coma and acute lung injury may develop in severe toxicity. Naphthalene skin exposure may cause hypersensitivity dermatitis. Repeated exposure may cause corneal ulceration, lenticular opacities, cataracts, headache, malaise and vomiting.

·      Haemolytic manifestations: Pallor, weakness, jaundice,cyanosis, haemolysis, haemolytic anaemia, methaemoglo-binaemia (Fig 27.3), hyperkalaemia, dysuria, haematuria, and dark urine (haemoglobinuria), albuminuria, oliguria, and acute renal failure. Cardiovascular shock can occur in patients with severe haemolytic anaemia. Metabolic acidosis may develop in patients with acute renal failure secondary to haemolysis.

o     Haematological Findings: Increased WBC count, fragmented RBC, anisocytosis, Heinz bodies, and poikilocytosis.

o     Infants and patients with G6PD deficiency, sickle cell anaemia, or sickle cell trait are more likely to develop haemolysis and/or methaemoglobinaemia.

·      Chronic exposure to naphthalene can result in aplastic anaemia, hepatic necrosis, and jaundice. Naphthalene and coal tar exposure have been associated with laryngeal and intestinal carcinoma.

Diagnosis

·      Obtain baseline CBC, electrolytes, glucose-6-phosphate dehydrogenase level, liver enzymes and renal function tests, urinalysis and urine dipstick test for haemoglobinuria.

·      Measurement of urinary metabolites (1-naphthol or mercap-turic acid) may help to confirm the diagnosis. Urinary naphthol levels may be utilised to monitor industrial creosote exposure (naphthalene is the most abundant compound found in creosote vapour).

·      X-ray: Abdominal radiographs may help differentiate between mothballs or other products which contain paradi-chlorobenzene (densely radiopaque) from those which contain naphthalene (radiolucent or faintly radiopaque).

Treatment

Acute exposure is treated on the same lines as in the case of aliphatic hydrocarbons.

·              Ingestion of one mothball may produce toxicity; patients with ingestion of more than this amount should be referred to a health care facility for gastric decontamination and observation. If laboratory findings are negative and the patient is asymptomatic during a 4 to 6-hour observation period, the patient may be discharged with instructions to return for a follow-up CBC and urinalysis for up to 5 days post-ingestion. Patients should be instructed to return if any gastrointestinal symptoms, pallor, dark or diminished urine output, or CNS symptoms develop.

·            Decontamination—

o     Induced emesis is more useful for mothballs because of their size. Do not induce vomiting if the patient has any evidence of lethargy or CNS depression.

o     Gastric lavage may be useful for ingestion of flakes, but its effectiveness may be limited by naphthalene’s poor water solubility. Mothballs dissolve slowly; gastric decontamination should be considered even in patients presenting late after ingestion.

o     Information on the benefit of activated charcoal is scant, but adsorption is thought to occur. Consider adminis-tration of activated charcoal after a potentially toxic ingestion (up to 1 hour).

o     Dermal Decontamination—Remove contaminated clothing and wash exposed area thoroughly with soap and water. Consider discarding contaminated clothing, as washing does not easily remove naphthalene.

·      Avoid oral administration of oil or fatty substances.

·      Control seizures.

·      Alkaline Diuresis—

o     Should be performed if there is evidence of haemolysis. This may prevent renal deposition of red blood cell break down products in the renal tubules and resultant renal failure.

o     Administer 1 to 2 mEq/kg of sodium bicarbonate as an intravenous bolus. Add 132 mEq (3 ampoules) sodium bicarbonate and 20 to 40 mEq potassium chloride (as needed) to one litre of dextrose 5% in water and infuse at approximately 1.5 times the maintenance fluid rate.

o     In patients with underlying dehydration additional administration of 0.9% saline may be needed to main-tain adequate urine output (1 to 2 ml/kg/hour).

o     Manipulate bicarbonate infusion to maintain a urine pH of at least 7.5. Additional sodium bicarbonate (1 to 2 mEq/kg) and potassium chloride (20 to 40 mEq/L) may be needed to achieve an alkaline urine. Do not administer potassium to an oliguric or anuric patient.

o     Obtain hourly intake/output and urine pH. Assure adequate hydration and renal function prior to alkalini-sation. Monitor fluid and electrolyte balance carefully.

o     Monitor blood pH, especially in intubated patients, to avoid severe alkalaemia. Administer furosemide as needed to maintain urine output.

·      Treat haemolysis with blood transfusion, packed red cell transfusions, or exchange transfusion.

·      Monitor methaemoglobin level and treat if symptomatic, or if methaemoglobin levels are greater than 30%. Treat with methylene blue 1 to 2 mg/kg/dose (0.1 to 0.2 ml/kg/dose) IV over 5 minutes as needed every 4 hours. It is important to remember that large doses of methylene blue may itself cause methaemoglobinaemia or haemolysis. Also, meth-ylene blue must not be administered if the patient has G6PD deficiency.

·              Haemodialysis may help enhance elimination, though it is not routinely recommended.

Forensic Issues

·              Most cases of exposure are accidental in nature.

·              A few are suicidal.

·              In the case of mothball ingestion (suicidal or accidental), sometimes there is confusion as to whether the active ingredient is naphthalene, camphor or paradichlorobenzene.

Differentiating between mothballs containing paradi- chlorobenzene (PDB), naphthalene and camphor:

––  Physical appearance—Naphthalene is dry, while PDB has a wet and oily appearance.

––Specific gravity—Distinguishing between camphor, naphthalene, and PDB mothballs can be done by testing whether they float or sink in a saturated solu- tion of salt water (4 ounces of tepid water to which 3 heaping tablespoons of table salt has been added and stirred vigorously until the salt will not dissolve any more). Camphor mothballs float in both water and salt solution. Naphthalene mothballs sink in water but float in saturated salt solution. PDB mothballs sink in both water and salt solution.

Solubility—PDB is more soluble in turpentine than naphthalene. A mothball of PDB will usually dissolve within 30 to 60 minutes whereas at least one fourth of the naphthalene will be left.

Heat—PDB produces a bright green colour in a bunsen burner flame; Naphthalene does not.

Melting point—PDB: 530 C; Naphthalene: 800 C. Placing a small piece of the mothball in a test tubeheated to 600 C in water bath may simplify the melting point test. PDB will liquefy within several minutes; naphthalene will remain intact.

Chemical test—If chloroform and ammonium chlo-ride powder are added to PDB no colour change occurs; naphthalene turns blue.