Kinetics of Methylmercury and Inorganic Mercury in Lactating and Nonlactating Mice

Abstract

The elimination of mercury was followed for 9 days (Days 10–19 of lactation) in milk and/or 21 days in blood and plasma of lactating and nonlactating mice administered a single iv injection of either203Hg-labeled methylmercuric chloride or203Hg-labeled mercuric chloride (0.5 mg Hg/kg body wt). Demethylation of methylmercury to inorganic mercury was taken into consideration by analyzing the data with a combined pharmacokinetic model based on the assumption of constant blood plasma ratios for methylmercury and inorganic mercury. A three-compartment model fitted the blood and plasma concentrations vs time profiles for both compounds. Plasma clearance and volume of distribution at steady state for methylmercury were 95.3 ml/h/kg and 18,500 ml/kg, respectively, in lactating mice, and significantly higher than in nonlactating mice with values of 47.1 ml/h/kg and 9400 ml/kg, respectively. The terminal half-lives of methylmercury in plasma were similar, 170 h in lactating and 158 h in nonlactating mice. No differences were observed between the pharmacokinetic parameters in lactating and nonlactating mice administered inorganic mercury. The lactational transfer of mercury was more efficient following administration of inorganic mercury than after administration of methylmercury, with a five times higher peak concentration in milk, higher milk:plasma concentration ratios, and 8% of the administered dose excreted in milk compared with 4% for methylmercury. Mercury concentrations in milk following an iv dose of inorganic mercury decreased with a terminal half-life of 107 h, whereas after administration of methylmercury, the concentration of total mercury in milk remained at an almost constant level during the whole period of investigation. There was a nonlinear relationship between mercury in milk and plasma following inorganic mercury administration. It is suggested that inorganic mercury enters the mammary gland by a carrier-mediated transport system, which is saturated at high plasma levels of inorganic mercury. The present study shows that physiological changes during lactation alter the pharmacokinetics for methylmercury in mice but not for inorganic mercury.