Liver toxicity due to 1,2-dichloropropane in the rat

Abstract

The effect of 1,2-dichloropropane on rat liver was studied after short (5 days) and long term (4 weeks) i.p. administration. Animals were injected daily with 10-500 mg/kg body wt 1,2-dichloropropane and biochemical and histological changes of liver were investigated. Treatment was monitored by measuring urinary mercapturic acid excretion. A significant increase of mercapturate excretion was observed at all dose levels, with no further increase during the treatment; at lower doses a return to baseline values occurred within 48 h after the end of treatment. Mercapturate excretion at the end of weeks 2, 3 and 4 of treatment was significantly lower than that observed at the end of week 1. The liver reduced glutathione content was different after single or repeated injections. A dose-dependent decrease of liver reduced glutathione was observed after a single injection and a dose-dependent increase after 4 weeks. The liver biochemical pattern after 4 weeks of treatment (characterized by a decrease of cytochrome P-450 and by an increase of reduced glutathione and glutathione S-transferase activity) suggests a hyperplastic evolution of the liver cells, probably a repair mechanism induced by early depletion of reduced glutathione. Light microscopy confirms that the prevalent alterations are regenerative in type (atypical mitosis and hyperplastic nodules). Areas of focal necrosis are isolated, and trend to disappear after long term treatment.