Toxicological Review for 2-Methylnaphthalene (CAS No. 91-57-6 ...

degrade surfactant. Altered activity of the growth factor (GM-CSF) may be due to the production of a
neutralizing antibody to GM-CSF. The inhibition of GM-CSF activity leads to immature macrophages,
undegraded surfactant, and surfactant buildup in the lung (Shah et al., 2000; Mazzone et al., 2001;
Seymour and Presneill, 2002).
In rare instances, several underlying conditions such as lysinuric protein intolerance, acute
exposure to silica dust or other inhaled environmental or industrial chemicals, immunodeficiency
disorders, malignancies and hematopoietic disorders rarely lead to the development of secondary
acquired proteinosis in humans. The low occurrence of pulmonary alveolar proteinosis following
exposure to silica and other inhaled environmental and industrial chemicals, reported in a few selected
case studies is most likely due to improved occupational health and safety standards (Seymour and
Presneill, 2002).
Congenital pulmonary alveolar proteinosis is an autosomal recessive genetic disorder that may
develop at birth or later in life. This form of pulmonary alveolar proteinosis is primarily believed to be
due to a mutation in the surfactant-associated protein B (SP-B) gene. In addition, a proportion of
infants affected with this form of the disorder are thought to have abnormalities in the receptor for GM-
CSF. Infants with congenital pulmonary alveolar proteinosis are affected with severe lung failure shortly
after birth and have a poor prognosis for survival (Shah et al., 2000; Seymour and Presneill, 2002).
Since whole lung lavage is difficult to perform on neonates, the most promising treatment for infants is
lung transplantation (Seymour and Presneill, 2002; Vaughan and Zimmerman, 2002). Difficulties
associated with whole lung lavage are magnified by the difficulty in passing the intubation tube and
instruments used to perform the lavage through the glottis of infants. Children that develop pulmonary
alveolar proteinosis later in life generally require repeated lavage treatments, but have greater chance of
survival (Seymour and Presneill, 2002; Vaughan and Zimmerman, 2002). In addition, children
heterozygous for the mutation in the SP-B gene most likely develop respiratory symptoms later in life
and have a more positive prognosis than children that are homozygous recessive for this disorder
(Seymour and Presneill, 2002).
It is unknown whether 2-methylnaphthalene by itself or its metabolites are responsible for the
development of pulmonary alveolar proteinosis. The higher incidence of pulmonary alveolar proteinosis
in mice exposed dermally to mixtures of 1- and 2-methylnaphthalene described above (Murata et al.,
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