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

treatment with 400 mg/kg 2-methylnaphthalene resulted in mortality for 4/5 mice. The surviving mouse
exhibited prominent sloughing of the bronchiolar lining, but a description of lung histopathology was not
reported for the nonsurvivors. In contrast, the same dose (400 mg/kg) of 2-methylnaphthalene without
glutathione depletion was not fatal, but resulted in the development of bronchiolar necrosis.
No bronchiolar necrosis was observed in male ddY mice given single intraperitoneal injections
of 200 mg/kg 2-methylnaphthalene. Pretreatment with diethylmaleate (600 :l/kg) 1 hour prior to
injection caused extensive sloughing and exfoliation of bronchiolar epithelial cells in all animals (5/5)
(Honda et al., 1990).
These observations suggest that metabolism of 2-methylnaphthalene may play a role in the
pathogenesis of pulmonary alveolar proteinosis in type II pneumocytes.
Additional evidence on whether 2-methylnaphthalene or its metabolites are responsible for lung
toxicity comes from intraperitoneal injection studies with 2-methylnaphthalene (Table 5). Castranova et
al. (1988) noted that two types of cells in the lung (type II pneumocytes in the alveoli and the
nonciliated Clara cells lining the bronchioles) exhibit substantial CYP enzyme activity and are expected
to metabolize foreign chemicals. Both cell types are secretory and are located in different parts of the
lung (Cho et al., 1995; Junqueira et al., 1995). While chronic exposure of B6C3F1 mice to 2-
methylnaphthalene in the diet appeared to target the type II pneumocytes, inducing pulmonary alveolar
proteinosis (Murata et al., 1992, 1997), acute intraperitoneal exposure of B6C3F1 mice to 2-
methylnaphthalene targeted the Clara cells, inducing bronchiolar necrosis characterized by Clara cell
abnormalities, focal or complete sloughing of Clara cells, and complete sloughing of the entire
bronchiolar lining (Buckpitt et al., 1986; Griffin et al., 1981, 1982, 1983; Honda et al., 1990;
Rasmussen et al., 1986). These observations provide indirect evidence that the development of both
types of toxic response may involve metabolism of 2-methylnaphthalene.
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