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Naphthalene poisoning (or mothball poisoning) is a form of toxicity that occurs when naphthalene is exposed within the body, usually causing haemolytic anaemia.

Naphthalene is a synthetically produced toxic polycyclic aromatic hydrocarbon that is white in appearance and is a commonly known as part of the composition of mothballs. Not only is it mainly found within mothballs, but can also be found from the production of crude oil or distillation of coal tar, and is frequently present when carbon based objects are burnt, such as in car exhausts and cigarette smoke. However it is unlikely to be exposed to enough naphthalene to warrant poisoning through burning of carbon based products. Ingestion of mothballs usually results in haemolytic anaemia, especially for newborns and for individuals who are affected by glucose-6-phosphate dehydrogenase deficiency. The main use for naphthalene is as an insect repellent or deodorant to prevent animals such as moths from eating clothing through repelling moths using the naphthalene sublimating producing fumes that poison moths.

Sources of Exposure
Naphthalene is used as a major product of mothballs, it is one of the most popular insect repellents used to deter moths, as well as skunks and raccoons from eating clothing due to the toxic fumes they expel.

Naphthalene's half life is only around 8 hours in length, being removed from the air through multiple hydroxyl radicals reacting, and slightly longer within the ground and soil, amounting to around seven days, due to biodegration and photolysis. Naphthalene is not prone to bio-accumulation due to the easily metabolism of naphthalene within its environment, thus exposure frequently occurs at sites where naphthalene is readily produced and potentially inhaled or ingested.

Naphthalene was introduced in 1841 by Rossbach and was primarily used as a way to counteract typhoid fever by using it as an antiseptic. Naphthalene was widely used in industrial sites within the 50s and only 9 cases were reported since 1947, as a result, the condition was had limited coverage within medical journals.

During the late 1950s the main source of naphthalene was using coal tar, resulting in industrial exposure to naphthalene, which was heavily reduced after the effects of naphthalene were observed over these years. In 1981-83 the National Institute for Occupational Safety and Health found numbers over 100,000 workers were potentially exposed to toxic levels of naphthalene, working primarily for major industrial and agricultural businesses. Exposure may often be a result of oral ingestion, inhalation, or through prolonged skin exposure.

Naphthalene has also had reported cases of toxicity during the production of phthalic anhydride, an industrial chemical used in large scale production of plasticizers. However the use of naphthalene during synthesis has declined in an attempt to reduce the amount of toxic fumes being potentially spread. As a result, recent discoveries of safer alternatives are being used over naphthalene, such as the catalytic oxidation of ortho-xylene.

Tobacco is also a source of exposure, creating an estimated range of 0.3 to 4 micrograms of naphthalene inhalation per cigarette that is consumed. A regular pack a day smoker on average would be inhaling amounts of 6-80 micrograms of naphthalene daily, which is a small and negligible amount of naphthalene, and is similar in magnitude to normal exposure near highways and areas where car exhaust is frequently inhaled or consumed. The napthalene within cigarettes is different to other sources of naphthalene. The naphthalene that is produced in cigarette smoke is bound to other particles and is not presented as a free vapour, meaning the exposure is small. Napthalene exposure is usually insignificant unless exposed to large amounts of naphthalene within production or being near proximity of a product that contains naphthalene. Naphthalene levels within an area are very unstable and frequently change over time and space. Due to this variance, sampling protocols must be conducted carefully and are usually analysed using different analytical methods.

Since mothballs that contain naphthalene are considered hazards, safer alternatives have been developed, such as the use of 1,4-dichlorobenzene, however, 1,4-dichlorobenzene has been delcared as a potential neurotoxin. 1,4-dichlorobenzene has been linked to potentially causing depression as a form of encephalopathy. This complication resulted with an increased use of Camphor as a moth repellent. The use of Camphor is frequently observed within the region of Asia. Camphor is not a carcinogen, but is still toxic if consumed in large doses.

Naphthalene has also been found to be secreted by termites in order to protect their nests. The termites use naphthalene to repel ants and any intruders who try to invade their nests. This naphthalene produced is not only toxic for the insects but can also affect humans in the same way. Naphthalene poisoning via termite nest was featured within "The Truth", episode eleven of season one of the American television medical drama House, where the final diagnosis ended up as acute naphthalene poisoning as a result of a termite nest being contained within the walls of the patients room, inhaling naphthalene in his sleep and becoming sick.

As mothballs are small white and shiny, they are a hazard towards children and should be placed in areas away from children due to their similar appearance to sweets. Deaths have been reported in small children ingesting mothballs as a result of their small and bright appearance. Mothballs undergo sublimation, which exposes toxic fumes that repel moths and other potential insects within the area, leading to danger if ingested.

Mothballs have also been reported to be used in cases of self-harm. The naphthalene is often consumed in large quantities through ingestion and inhalation of mothballs, resulting in increased vertigo and abdominal pain leading to haemolytic anaemia. The Centres for Disease control estimated that in the years of 1970 to 1980,  287,000 individuals suicides were confirmed through naphthalene poisoning by ingestion of mothballs within the United States.

Naphthalene can also form polychlorinated naphthalene, which is included within the annexes of the Stockholm Convention on Persistent Organic Pollutants. Although different to naphthalene, they can defragment to form naphthalene and are found within many food products and unintentional creation through thermal processes, leading to indirect naphthalene contamination.

Treatment
Treatment of naphthalene toxicity usually follows the same treatments involved for haemolytic anaemia, which involves a series of blood transfusions, in order to restore healthy levels of haemoglobin. This may include intravenous methylene blue and ascorbic acid. The methylene blue allows the methaemoglobin to be converted to haemoglobin. Supportive treatment is also usually provided, depending on the severity of the toxicity, that resulted in the anaemia.

Ascorbic acid is used to treat methemoglobinemia, a symptom of naphthalene poisoning and is used when methylene blue is not available, or in conjunction with methylene blue in order to restore haemoglobin count.

Symptoms
Naphthalene's formula is C10H8 and is an organic compound. Symptoms of naphthalene exposure can be observed with levels of naphthalene as low as 20 parts per billion. This may include headache, nausea, vomiting, abdominal pain, malaise, confusion, anaemia, jaundice and renal disease.

Diarrhoea and bloody and discoloured (usually dark) urine have also been reported as potential symptoms, alongside the formation of cataracts and retinal haemorrhage within those faced with prolonged exposure.

Seizures have also been reported as a potential symptom of naphthalene poisoning.

Mechanisms of toxicity
According to the International Agency for Research on Cancer, naphthalene is possibly carcinogenic to humans (Group 2B), as there is inadequate evidence in humans for the carcinogenicity of naphthalene, however there is sufficient evidence in experimental animals for the carcinogenicity of naphthalene. The carcinogenicity was tested on rats in mice, via intraperitoneal administration and subcutaneous administration, of newborns and adult rats, providing evidence of tumours. The IARC also discovered that naphthalene toxicity also had potential to cause cataracts in humans, rats, rabbits and mice, however the tests were considered inefficient to substantiate a diagnosis resulting in naphthalene as a potential carcinogen classification. Likewise, the European Chemical agency classified naphthalene as Group C, a possible human carcinogen. This was classified due to lack of evidence of naphthalene alone causing carcinogenic properties in rats, and limited human contact with naphthalene within industrial environments.

Haemolysis occurs either through haemoglobin defects, such as formation of Heinz bodies, or cell membrance defects, especially those with glucose-6-phosphate dehydrogenase deficiency and a low tolerance to oxidative stress. This haemolysis is usually accompanied by neurological effects such as vertigo, lethargy and convulsions, usually caused by cerebral edema. Gastrointentinal bleeding may also appear as a symptom after ingestion of mothballs, especially for those who are younger.

Acute exposure to naphthalene is unlikely to cause toxicity and must be ingested unless prolonged contact is provided along the skin or eyes. After ingestion of mothballs containing naphthalene, symptoms of haemolytic anaemia are presented and treated normally through the use of methylene blue and regular blood transfusions, and patients are usually released after 6-10 days depending on their haemoglobin levels.

Repeated naphthalene exposure has also been found to potentially cause airway epithelial damage, aberrant repair, and inflammation. Greater numbers of peribronchial Mac-3-positive macrophages and CD3-positive T-cells were observed throughout the airways which displays acute inflammation within the airways.

Naphthalene metabolites of 1,2-hydroxynaphthalene has also been found to be a mechanism of oxidative DNA damage within humans. In the presence of the reduced form of nicotinamide adenine dinucleotide (NADH). The damaging activity of the DNA of the activity of 1,2-hydroxynaphthalene was observed at much larger levels. 1,2-hydroxynaphthalene is reduced by NADH to be formed as a part of the redox cycle, resulting in the speeding up of DNA damage, however, this is only presented within larger prolonged exposure to naphthalene, values that are unrealistic for any individual not working near a place where naphthalene production occurs.

Biomarkers of excessive exposure
1,2-Dihydroxynaphthalene has been used as a potential biomarker of excessive exposure to naphthalene levels and was tested on smokers and those exposed to naphthalene among the working population. After collecting the urine samples of multiple workers, Median 1,2-Dihydroxynaphthalene values were 1012 micrograms per litre for those exposed to naphthalene and 8 micrograms per litre for those who were in the control group indicating that it is useful as a biomarker for exposure within humans. The median results for the concentrations of 1,2-Dihydroxynaphthalene were about ten times the amount of the standard markers of 1-naphthol and 2-naphthol within human urine.

Restriction of Mothballs
As a result of naphthalene mothballs being small and white, the European Union enforced a ban on the distribution and production of mothballs containing naphthalene in 2008, as a part of the new regulations of the Registration, Evaluation and Authorisation of Chemicals (REACH), regulating chemical use within its representative countries.

In 2014, New Zealand banned the distribution of mothballs after the Environmental Protection Agency determined that the chemicals were not safe enough to warrant its viability as a non-toxic pesticide.

Mothballs are restricted within Australia, only being distributed in forms that prevent them from being ingested.