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

weeks, no evidence for exposure-related bronchiolar lesions (Clara cell toxicity) were found (Murata et
al., 1993, 1997). The finding may be related to observations suggesting that Clara cells can develop
resistance to naphthalene toxicity (Lakritz et al., 1996). Pretreatment of male Swiss-Webster mice with
a nontoxic initial dose of 200 mg/kg naphthalene for 7 days made the Clara cell lining of the bronchioles
more resistant to a subsequent dose of 300 mg/kg naphthalene compared with mice given only 300
mg/kg naphthalene without pretreatment (Lakritz et al., 1996). The authors suggested that reduced
expression of CYPIIB, CYPIIF, CYP reductase, and secretory protein led to this increased resistance
in the Clara cells. However, the possible development of Clara cell resistance to the acute toxicity of
2-methylnaphthalene has not been studied.
There are limited data to suggest that rats may be less sensitive than mice to lung damage
caused by acute exposure to 2-methylnaphthalene. Wistar rats given intraperitoneal doses of 140
mg/kg 2-methylnaphthalene did not lead to pulmonary toxicity (Dinsdale and Verschoyle, 1987). In
contrast, bronchiolar necrosis was induced in Swiss-Webster mice injected with approximately the
same dose (Rasmussen et al., 1986) and C57BL/6J and DBA/2J mice injected with 100 mg/kg 2-
methylnaphthalene (Griffin et al., 1981, 1982, 1983). The data are consistent with findings that rats are
more resistant than mice to the acute Clara cell toxicity of naphthalene (NTP, 2000; O’Brien et al.,
1985). No data are available for interspecies comparisons of the chronic toxicity of 2-
methylnaphthalene.
2-Methylnaphthalene does not appear to target the liver or kidneys. No histopathological
damage in these organs was reported in mice following oral exposure to doses as high as 114 mg/kg-
day for 81 weeks (Murata et al., 1997) or following acute intraperitoneal injections to doses associated
with mortality (1,000 mg/kg) (Griffin et al., 1981, 1983). Additionally, no changes in clinical chemistry
markers of liver or kidney damage were seen in the 81-week study (Murata et al., 1997). Rasmussen
et al. (1986) reported minimal changes in the livers of mice intraperitoneally injected with 2-
methylnaphthalene, but did not further describe these changes or specify the dose levels at which they
occurred. In addition, in vitro assays have demonstrated cytotoxicity caused by 2-methylnaphthalene
exposure in Sprague-Dawley rat cortical tubular epithelial cells and glomerular mesangial cells (Bowes
and Ramos, 1994; Parrish et al., 1998; Zhao and Ramos, 1998), but the relevance of these changes is
suspect given the absence of kidney changes in the acute and chronic in vivo exposure studies with 2-
methylnaphthalene in mice.
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