Toxicology Brief: Moth repellent toxicosis

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Jan 01, 2005



Between 2002 and 2004, ASPCA Animal Poison Control Center (APCC) staff members consulted on 158 cases of moth repellent ingestion. In most instances, the exposure was oral, but dermal and inhalation exposures were also reported. Naphthalene was the active ingredient in 83% of the cases, and paradichlorobenzene was the active ingredient in 17%. Naphthalene, a bicyclic aromatic hydrocarbon, is a natural component of fossil fuels, such as petroleum and coal. It is also produced when wood and tobacco are burned.1 Paradichlorobenzene, an organochlorine insecticide, is considered to be half as toxic as naphthalene.2 Many moth repellent products contain nearly 100% naphthalene or paradichlorobenzene. The products can be formulated into balls, crystals, or flakes.

PHARMACOKINETICS

Naphthalene evaporates easily and has a strong odor that repels moths. People can detect it in the air at concentrations of 84 ppb.1 Naphthalene can be inhaled, ingested, or absorbed transdermally. It is soluble in oils and fats, so dermal absorption is increased if oils have been previously applied to the skin. Similarly, oral absorption increases when naphthalene is coadministered with a fatty product such as corn oil.1,3 Paradichlorobenzene also has a characteristic penetrating odor and is well-absorbed orally and by inhalation.4 As with naphthalene, drinking milk or eating a fatty meal after oral exposure to paradichlorobenzene increases its absorption.4,5 Mothballs of either type may take several days to dissolve in the gastrointestinal tract, so prolonged absorption is possible.2

Naphthalene is carried to other organs once it enters the bloodstream, regardless of the absorption route. After a single dose of naphthalene in pigs, the highest concentration of naphthalene was found in adipose tissue. The kidneys, liver, and lungs contained the next highest concentrations, respectively. But pigs given multiple doses of naphthalene had the highest concentrations in the lungs with little in adipose tissue.1 The highest tissue concentrations of paradichlorobenzene are found in adipose tissue.4 Both naphthalene and paradichlorobenzene are found in milk and are able to cross the placenta.3,5

The metabolism of naphthalene is complex. The initial metabolite, a 1,2-oxide, is produced in the liver by the monooxygenase enzymes (P450). Naphthalene 1,2-oxide can then form epoxides or quinones that may cause cellular damage, or it can be conjugated with glutathione to nontoxic metabolites.6 Additionally, some metabolites are conjugated with sulfate or glucuronic or mercapturic acid.1,3 Paradichlorobenzene is oxidized to phenolic compounds and then undergoes rapid conjugation with sulfate and glucuronide.5 The metabolites of both naphthalene and paradichlorobenzene are excreted primarily through urine, but some metabolites are excreted in bile.1,3-5

TOXICITY

Paradichlorobenzene is considered less toxic than naphthalene. In rats, the oral LD50 of naphthalene is 1.8 g/kg,7 whereas the oral LD50 of paradichlorobenzene is 3.8 g/kg.5 Dogs ingesting 1.5 g/kg of paradichlorobenzene did not develop clinical signs of toxicosis,4 but hemolytic anemia was reported in a dog that received a single 1,525-mg/kg dose of naphthalene and in another dog that received about 263 mg/kg/day naphthalene for seven days.1 One mothball of either type weighs about 5 g. Less than one naphthalene mothball may cause clinical signs of toxicosis in children, but accidentally ingesting up to one paradichlorobenzene mothball is generally well-tolerated.3,4

CLINICAL SIGNS OF TOXICOSIS

Naphthalene

Hematologic effects have been reported in dogs after naphthalene ingestion,1,8 and cataracts have developed in laboratory animals.1 In the ASPCA APCC database, the most commonly reported clinical signs after ingesting naphthalene-containing moth repellent products were vomiting, lethargy, and anorexia (ASPCA APCC Database: Unpublished data, 2004). Seizures and methemoglobinemia were also reported.