Napthalene and haemolytic anaemias

A recent Medical Journal of Australia article:

Risk of brain damage in babies from naphthalene in mothballs: call to consider a national ban
William O Tarnow-Mordi, Nick J Evans, Kei Lui, Brian Darlow, on behalf of the Advisory Committee of the Australian and New Zealand Neonatal Network — Med J Aust 2011; 194 (3): 150.

on naphthalene toxicity in neonates with a G6PD deficiency lead me to wonder about the suspectability of adults with this condition to naphthalene. If babies are affected by clothing that has been mothballed, then an increase in haemolytic anaemias at the beginning of winter in people with G6PD deficiencies could be expected, when they put on mothballed warm clothing.

I suspect that the use of mothballs is less common than in the past, particularly with the use of vacuum bags to store seasonal clothes.

It turns out it is mentioned in the 2001 ACGIH TLV Documentation, but there has been a more recent publications which may have more recent findings.

The mention of naphthalene also reminded me of:

• a ventilation hood I designed for an etymologist to safety work on trays of butterflies. The trays had a moat of naphthalene around the edge. My solution was to design an enclosure with a transparent top so that the air velocity was low enough to not damage to wings of the the butterflies. The image of trays of pinned butterflies without any wings struck me at the time.
• using naphthalene to test my special permeation cell for solids and other difficult chemicals. There is little data on permeation of chemical solids through gloves, though this is a know issue, particularly with agrochemicals. See O’Callaghan, K., P. M. Fredericks, D. W, Bromwich. (2001). “Evaluation of Chemical Protective Clothing by FT-IR/ATR Spectroscopy.” Applied Spectroscopy 55(5). PDF

The recent Australian study referred to an EU study:

European Chemicals Bureau. European Union risk assessment report. Naphthalene. CAS No: 91-20-3. EINECS No: 202-049-5. Luxembourg: Office for Official Publications of the European Communities, 2003. http://ecb.jrc.ec.europa.eu/documents/Existing-Chemicals/RISK_ASSESSMENT/REPORT/naphtha lenereport020.pdf .

This study notes:

Individuals who are deficient in G-6-PD are particularly sensitive to haemolytic anaemia produced by naphthalene (Gosselin et al., 1984). This deficiency is genetically determined and occurs more often in males. The defect results in an inability by the red blood cell to maintain a balance between reduced and oxidised glutathione which in turn results in an increased susceptibility to oxidative attack by exogenous chemicals. It seems probable that the oxidative attack, following exposure to naphthalene, can occur following redox cycling of the naphthalene metabolites 1-naphthol and the quinone. The deficiency is known to be more common in Blacks, Greeks, Italians, Sephardic Jews, Orientals and Filipinos.

Gosselin RE, Smith RP and Hodge HC (1984). Clinical Toxicology of Commercial Products. 5 ed. Williams and Wilkins, London.

The 2010 ACGIH entry for naphthalene gives a TLV unchanged from the 2001 TLV Documentation

2010 TLV^® Chemical Substance Search

The 2001 ACGIH TLV Documentation for naphthalene notes:

A hypersusceptibility, based on a congenital deficiency of erythrocyte glucose-6- phosphate dehydrogenase activity, was recognized (35)  and is more common among Asians, Arabs, Caucasians of Latin ancestry, and American and African Blacks.(36)  Males are particularly sensitive.

Here, reference 35 is to:

Dacie, J.V.: The Haemolytic Anemias, Congenital and Acquired, Part IV, Drug-Induced Haemolytic Anemias, Paroxysmal Nocturnal Haemoglobinuria, Haemolytic Disease of the Newborn, 2nd ed. Grune & Stratton, New York (1967)

A quick serach of Pubmed  for naphthalene with various search terms gave

• Ostlere, L., R. Amos, et al. (1988). “Haemolytic anaemia associated with ingestion of naphthalene-containing anointing oil.” Postgrad Med J 64(752): 444-6.
• Magee, B., J. Samuelian, et al. (2010). “Screening-level population risk assessment of nasal tumors in the US due to naphthalene exposure.” Regul Toxicol Pharmacol 57(2-3): 168-80.
• Santhanakrishnan, B. R., G. Ranganathan, et al. (1973). “Naphthalene induced haemolytic anaemia with haemoglobinuria.” Indian J Pediatr 40(304): 195-7.
• Trevisan, A., M. Rossi di Schio, et al. (2001). “Haemolytic anaemia after oral self-giving of naphthalene-containing oil.” J Appl Toxicol 21(5): 393-6.

The abstract from Magee, B., J. Samuelian, et al. (2010)  is interesting.

Several naphthalene Unit Risk Factors (URFs) were proposed by the US Environmental Protection Agency in 2004 using data on the development of olfactory epithelial neuroblastomas and nasal respiratory epithelial adenomas in rats, but these URFs may be inappropriate and unnecessarily conservative for estimating human cancer risks. The purpose of the present exercise was to perform a screening-level population risk assessment of the US population to compare the observed number of naphthalene-induced nasal tumors in the US to the number that would be predicted if the URFs for naphthalene were as proposed. Nine scenarios were evaluated to represent the range of exposures individuals have typically experienced. Results indicate that the total predicted burden of naphthalene-induced nasal tumors per year in the US (65,905 rare nasal tumors, of which 29,121 are olfactory epithelial neuroblastomas) is much greater than the number of these tumors actually observed per year (910 total nasal tumors, of which 66 are olfactory neuroblastomas) over the period 1973-2006. This suggests that using rat nasal tumor data to derive a naphthalene URF for humans should be re-evaluated.

Looks like reviewing naphthalene toxicity is somewhere in my ToDo list.