Naphthalene Toxicity in Clinical Practice

Author(s): Ashok Kumar Pannu*, Vidhi Singla

Journal Name: Current Drug Metabolism

Volume 21 , Issue 1 , 2020

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Graphical Abstract:


Background: Naphthalene ingestion and skin or inhalational exposure (accidental or deliberate) is an under-recognized cause of a severe toxidrome in regions where it is commonly used (e.g., mothballs in households).

Methods: This review is an update for the clinicians to understand the pharmacology, clinical features, laboratory evaluation, and treatment for naphthalene toxicity. High-quality literature for the past eight decades was collected and reviewed in this article. Several landmark articles were reviewed using PubMed, EMBASE Ovid, and the Cochrane Library, which have essential implications in the current toxicology practice.

Results and Conclusion: Naphthalene toxicity usually occurs abruptly and leads to acute hemolysis, methemoglobinemia, renal failure, respiratory depression, and acute brain dysfunction that are difficult to manage. The toxicity is more marked in patients with G6PD deficiency and associated with high morbidity and mortality. The management should mainly focus on high-quality supportive care; however, severe methemoglobinemia (>20-30%) requires specific therapy with intravenous methylene blue. Methylene blue is a highly effective agent but contraindicated in severe G6PD deficiency.

Keywords: Naphthalene, mothball, poisoning, hemolysis, methemoglobinemia, methylene blue.

Stohs, S.J.; Ohia, S.; Bagchi, D. Naphthalene toxicity and antioxidant nutrients. Toxicology, 2002, 180(1), 97-105.
[] [PMID: 12324202]
The National Institute for Occupational Safety and Health (NIOSH) Naphthalene, Immediately Dangerous to Life or Health Concentrations (IDLH) Documentation, . 1994. idlh/91203.html
United States Department of Health and Human Services: Toxicological profile for naphthalene, 1-methylnaphthalene, and 2- methylnaphthalene. 2005. asp?id=240&tid=43
Goldfrank, L.R. Goldfrank’s Toxicological Emergencies, 11th Edition.; Appleton & Lange: New York, 2019.
Galbo, M.J.M.S. Naphthalene and paradichlorobenzene.Poisoning & Drug Overdose; Olson, K.R., Ed.; The McGraw-Hill Companies: New York, 2018, pp. 335-337.
Smillie, W.G. Betanaphthol poisoning in the treatment of hookworm disease. JAMA, 1920, 74, 1503-1506.
Siegel, E.; Wason, S. Mothball toxicity. Pediatr. Clin. North Am., 1986, 33(2), 369-374.
[] [PMID: 3515301]
Valaes, T.; Doxiadis, S.A.; Fessas, P. Acute hemolysis due to naphthalene inhalation. J. Pediatr., 1963, 63, 904-915.
[] [PMID: 14071045]
Bates, N. Mothball poisoning. Emerg. Nurse, 2002, 10(2), 24-28.
[] [PMID: 12032983]
Dawson, J.P.; Thayer, W.W.; Desforges, J.F. Acute hemolytic anemia in the newborn infant due to naphthalene poisoning: report of two cases, with investigations into the mechanism of the disease. Blood, 1958, 13(12), 1113-1125.
[] [PMID: 13596416]
Lim, H.C.; Poulose, V.; Tan, H.H. Acute naphthalene poisoning following the non-accidental ingestion of mothballs. Singapore Med. J., 2009, 50(8), e298-e301.
[PMID: 19710964]
Gidron, E.; Leurer, J. Naphthalene poisoning. Lancet, 1956, 270(6910), 228-231.
[] [PMID: 13287114]
Fanburg, S.J. Exfoliative dermatitis due to naphthalene: Report of an eruption resembling mycosis fungoides. Arch. Dermatol., 1940, 42, 53-58.
Feuillet, L.; Mallet, S.; Spadari, M. Twin girls with neurocutaneous symptoms caused by mothball intoxication. N. Engl. J. Med., 2006, 355(4), 423-424.
[] [PMID: 16870927]
Weintraub, E.; Gandhi, D.; Robinson, C. Medical complications due to mothball abuse. South. Med. J., 2000, 93(4), 427-429.
[] [PMID: 10798515]
Santucci, K.; Shah, B. Association of naphthalene with acute hemolytic anemia. Acad. Emerg. Med., 2000, 7(1), 42-47.
[] [PMID: 10894241]
Sahni, M.; Vibert, Y.; Bhandari, V.; Menkiti, O. Newborn infant with mothball toxicity due to maternal ingestion. Pediatrics, 2019, 143(6)e20183619
[] [PMID: 31064798]
Schafer, W.B. Acute hemolytic anemia related to naphthalene; report of a case in a newborn infant. Pediatrics, 1951, 7(2), 172-174.
[PMID: 14827617]
Viravaidya, K.; Shuler, M.L. Prediction of naphthalene bioaccumulation using an adipocyte cell line model. Biotechnol. Prog., 2002, 18(2), 174-181.
[] [PMID: 11934283]
Bogen, K.T.; Benson, J.M.; Yost, G.S.; Morris, J.B.; Dahl, A.R.; Clewell, H.J., III; Krishnan, K.; Omiecinski, C.J. Naphthalene metabolism in relation to target tissue anatomy, physiology, cytotoxicity and tumorigenic mechanism of action. Regul. Toxicol. Pharmacol., 2008, 51(2)(Suppl.), S27-S36.
[] [PMID: 18191315]
Buckpitt, A.; Boland, B.; Isbell, M.; Morin, D.; Shultz, M.; Baldwin, R.; Chan, K.; Karlsson, A.; Lin, C.; Taff, A.; West, J.; Fanucchi, M.; Van Winkle, L.; Plopper, C. Naphthalene-induced respiratory tract toxicity: metabolic mechanisms of toxicity. Drug Metab. Rev., 2002, 34(4), 791-820.
[] [PMID: 12487150]
MacKell, J.V.; Rieders, F.; Brieger, H.; Bauer, E.L. Acute hemolytic anemia due to ingestion of naphthalene moth balls. I. Clinical aspects. Pediatrics, 1951, 7(5), 722-728.
[PMID: 14843791]
Zinkham, W.H.; Childs, B. A defect of glutathione metabolism in erythrocytes from patients with a naphthalene-induced hemolytic anemia. Pediatrics, 1958, 22(3), 461-471.
[PMID: 13578538]
Guay, J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth. Analg., 2009, 108(3), 837-845.
[] [PMID: 19224791]
Luzzatto, L.; Arese, P. Favism and glucose-6-phosphate dehydrogenase deficiency. N. Engl. J. Med., 2018, 378(1), 60-71.
[] [PMID: 29298156]
Zuelzer, W.W.; Apt, L. Acute hemolytic anemia due to naphthalene poisoning; a clinical and experimental study. J. Am. Med. Assoc., 1949, 141(3), 185-190.
[] [PMID: 18139544]
Chusid, E.; Fried, C.T. Acute hemolytic anemia due to naphthalene ingestion. AMA Am. J. Dis. Child., 1955, 89(5), 612-614.
[] [PMID: 14360746]
Ostlere, L.; Amos, R.; Wass, J.A. Haemolytic anaemia associated with ingestion of naphthalene-containing anointing oil. Postgrad. Med. J., 1988, 64(752), 444-446.
[] [PMID: 3211822]
Deo, P.; Sahu, K.K.; Dhibar, D.P.; Varma, S.C. Naphthalene ball poisoning: a rare cause of acquired methaemoglobinaemia. BMJ Case Rep.,, 2016., 2016bcr2016215102
[] [PMID: 27226127]
Chugh, K.S.; Singhal, P.C.; Sharma, B.K.; Mahakur, A.C.; Pal, Y.; Datta, B.N.; Das, K.C. Acute renal failure due to intravascular hemolysis in the North Indian patients. Am. J. Med. Sci., 1977, 274(2), 139-146.
[] [PMID: 602954]
Mlynek, K.; Thusius, N.; Sola, C.; Romanowicz, M. Long term consequences of chronic naphthalene poisoning in a patient with a mothball use disorder. Psychosomatics.,, 2019, pii, S0033-3182(19), 30082-9.
Ekambaram, S.; Chandan Kumar, K.M.; Mahalingam, V. Acute kidney injury: A rare complication of mothball (Naphthalene) poisoning. Saudi J. Kidney Dis. Transpl., 2017, 28(6), 1412-1415.
[] [PMID: 29265056]
Choi, J.; Park, S.H.; Park, M.J.; Jeon, S.H. Death from naphthalene poisoning manifesting as toxic hepatitis: an autopsy case. Korean J. Leg. Med., 2017, 41(4), 137-140.
Owa, J.A.; Izedonmwen, O.E.; Ogundaini, A.O.; Ogungbamila, F.O. Quantitative analysis of 1-naphthol in urine of neonates exposed to mothballs: the value in infants with unexplained anaemia. Afr. J. Med. Med. Sci., 1993, 22(1), 71-76.
[PMID: 7839885]
van Solinge, W.W.; van Wijk, R. Erythrocyte enzyme disorders; Williams Hematology, 2016, pp. 689-723.
Volney, G.; Tatusov, M.; Yen, A.C.; Karamyan, N. Naphthalene toxicity: methemoglobinemia and acute intravascular hemolysis. Cureus, 2018, 10(8)e3147
[] [PMID: 30345203]
Wright, R.O.; Lewander, W.J.; Woolf, A.D. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann. Emerg. Med., 1999, 34(5), 646-656.
[] [PMID: 10533013]
Fountain, J.S.; Beasley, D.M. Activated charcoal supercedes ipecac as gastric decontaminant. N. Z. Med. J., 1998, 111(1076), 402-404.
[PMID: 9830429]
Ruha, A.M.; Levine, M. Central nervous system toxicity. Emerg. Med. Clin. North Am., 2014, 32(1), 205-221.
[] [PMID: 24275175]
Coleman, M.D.; Coleman, N.A. Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf., 1996, 14(6), 394-405.
[] [PMID: 8828017]
Harris, J.C.; Rumack, B.H.; Peterson, R.G.; McGuire, B.M. Methemoglobinemia resulting from absorption of nitrates. JAMA, 1979, 242(26), 2869-2871.
[] [PMID: 513256]
Harrison, M.R. Toxic methaemoglobinaemia. A case of acute nitrobenzene and aniline poisoning treated by exchange transfusion. Anaesthesia, 1977, 32(3), 270-272.
[] [PMID: 848728]
Liao, Y.P.; Hung, D.Z.; Yang, D.Y. Hemolytic anemia after methylene blue therapy for aniline-induced methemoglobinemia. Vet. Hum. Toxicol., 2002, 44(1), 19-21.
[PMID: 11824767]
Rino, P.B.; Scolnik, D.; Fustiñana, A.; Mitelpunkt, A.; Glatstein, M. Ascorbic acid for the treatment of methemoglobinemia: the experience of a large tertiary care pediatric hospital. Am. J. Ther., 2014, 21(4), 240-243.
[] [PMID: 24914501]
Gupta, K.; Kakar, T.S. Hazardous Chemical emergencies and poisonings. N. Engl. J. Med., 2019, 381(4), 392.
[] [PMID: 31340111]

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Article Details

Year: 2020
Published on: 13 May, 2020
Page: [63 - 66]
Pages: 4
DOI: 10.2174/1389200220666191122110036
Price: $65

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