ALKYLNAPHTHALENE .11. PULMONARY TOXICITY OF NAPHTHALENE, 2-METHYLNAPHTHALENE, AND ISOPROPYL-NAPHTHALENES IN MICE

Pulmonary toxicity of naphthalene (NAP), 2-methylnaphthalene (2-MN), 2-isopropylnaphthalene (2-IPN) and 2,6-diisopropylnaphthalene (2,6-DIPN) was studied in mice. Twenty four h after the intraperitoneal (i.p.) administration of NAP (200 mg/kg (1.6 mmol)) or 2-MN (400 mg/kg (2.8 mmol)), pulmonary damage was detected. Prior treatment with diethyl maleate resulted in enhancement of NAP and 2-MN-induced bronchiolar damage. In contrast to the effects of NAP and 2-MN, injections of 2-IPN (3000 mg (17.6mmol)/kg) and 2,6-DIPN (3000 mg (14.2 mmol)/kg) did not cause detectable pulmonary damage. Injections of NAP and 2-MN caused considerable depletion of pulmonary reduced glutathione (GSH), while injections of 2-IPN and 2,6-DIPN caused only a slight depletion. There were general decreases in the binding of the compounds to lung slices with increasing number of carbons of the alkyl substituent. Pretreatment with a cytochrome P-450 inducer (£-naphthoflavone) increased the binding of NAP, 2-MN, and 2-IPN to lung slices. Treatments with NAP, 2-MN, 2-IPN and 2,6-DIPN did not affect the lipid peroxidation or phospholipid contents in the lung. These results suggest that the difference in pulmonary toxicity among NAP, 2-MN, 2-IPN, and 2,6-DIPN may be dependent on the ability of these compounds to irreversibly bind to lung tissue. © 1990, The Pharmaceutical Society of Japan. All rights reserved.