Critical assessment of the genetic toxicity of naphthalene

Studies demonstrating that naphthalene produces respiratory tract tumors in mice and rats raised the question of whether humans are at risk for cancer, at environmental or workplace concentrations of naphthalene. Arguments in favor of a threshold-dependent mode of action for tumor induction have been based on the facts that naphthalene does not appear to bind to DNA in vivo and that the rodent tumors occurred at high dose levels associated with substantial target site toxicity. A summary of more than 45 publications describing results for naphthalene in genetic toxicology test methods shows that 80% of the studies reported found no evidence of genotoxicity for naphthalene and that some of the studies which reported positive finding were technically unsuited to study this class of chemicals and, therefore, generated unreliable data. The remaining positive findings for naphthalene were all consistent with secondary DNA effects produced by toxicity from naphthalene alone or one of its metabolites. Based on the data reviewed in this report, it is not apparent that genetic lesions produced by naphthalene or any of its metabolites drive the tumorigenic activity.