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

for the 142 and 284 mg/kg mice, compared with 0.4 for control mice.
Electron microscopy of lung tissue collected from exposed mice at 6, 12, or 24 hours after
injection showed Clara cell flattening, cytoplasmic vacuolization, loss of smooth endoplasmic reticulum,
reduced number of microvilli, prominent ribosomes, and electron-dense mitochondria. Cytoplasmic
vacuolization was reported to have occurred in control mice, but not as extensively as in exposed mice.
Clara cell ultrastructural changes were reported to have increased in severity with increasing dose, from
71 to 427 mg/kg. Airways in mice from the highest dose group (427 mg/kg) were reported to be the
most severely affected showing, in addition to Clara cell effects, flattened and vacuolated ciliated cells
with dilated cisternae of the granulated endoplasmic reticulum, electron-dense mitochondria, and
prominent ribosomes. At 1, 3, and 7 days after injection, cell proliferation indices in bronchiolar
epithelial cells from the 284 mg/kg dose group increased by 3-, 32-, and 3-fold, compared with vehicle
control values. Cell proliferation indices in alveolar cells from the 284 mg/kg dose group showed a
similar response over time, but were not as greatly increased as in bronchiolar cells. Examination of
liver and kidney sections from exposed mice revealed minimal changes in the liver and no changes in the
kidney. The study report did not further describe these changes or specify the dose levels at which they
occurred.
Buckpitt et al. (1986) administered single doses of 0 or 300 mg/kg 2-methylnaphthalene to
male Swiss-Webster mice (5/group) by intraperitoneal injection, with sacrifice 24 hours later.
Histological examinations identified bronchiolar necrosis in all treated animals, and no lesions among
controls. Pulmonary necrosis was considered moderate (bronchiolar epithelial cell swelling,
vacuolization, and exfoliation) for 3/5 mice and severe (extensive sloughing in terminal and larger
airways with widespread exfoliation) for 2/5 mice. For this study, the LOAEL for bronchiolar necrosis
in male Swiss Webster mice is 300 mg/kg 2-methylnaphthalene.
Female Wistar rats (numbers not provided) given single intraperitoneal injections of 0 or 1
mmol/kg (142 mg/kg) of 2-methylnaphthalene showed no evidence of pulmonary necrosis (Dinsdale
and Verschoyle, 1987).
4.4.2. Studies with Methylnaphthalene Mixtures
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