Environmental Toxicology and Pharmacology 42 (2016) 163–169 Contents lists available at ScienceDirect Environmental Toxicology and Pharmacology j o ur na l ho mepage: www.elsevier.com/locate/etap Partitioning and kinetics of methylmercury among organs in captive mink (Neovison vison): A stable isotope tracer study R. Douglas Evans a,b,∗ , Brendan Hickie a , Kirsti Rouvinen-Watt c , Wei Wang a a School of the Environment, Trent University, Peterborough, ON K9L 0G2, Canada b Water Quality Centre, Trent University, Peterborough, ON K9L 0G2, Canada c Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada a r t i c l e i n f o Article history: Received 1 October 2015 Received in revised form 8 January 2016 Accepted 9 January 2016 Available online 13 January 2016 Keywords: Mercury Stable isotopes Kinetics Distribution Mink a b s t r a c t Despite the importance of methylmercury (MeHg) as a neurotoxin, we have relatively few good data on partitioning and kinetics of MeHg among organs, particularly across the blood–brain barrier, for mam- mals that consume large quantities of fish. The objective of this study was to determine the partition coefficients between blood and brain, liver and kidney and fur for MeHg under steady-state conditions and to measure the half-lives for MeHg in these organs. Captive mink (Neovison vison) were fed a diet enriched with two stable isotopes of Hg, Me 199 Hg and Me 201 Hg for a period of 60 days. After a period of 10 days the diet was changed to contain only Me 201 Hg so that, between days 10 and 60, we were able to measure both uptake and elimination rates from blood, brain, liver kidney and fur. Liver and kidney response was very rapid, closely following changes in blood concentrations but there was a small lag time between peak blood concentrations and peak brain concentrations. Half-lives for MeHg were 15.4, 10.2 and 13.4 days for brain, liver and kidney, respectively. There was no measurable conversion of the MeHg to inorganic Hg (IHg) in the brain over the 60 day period, unlike in liver and kidney. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Mercury (Hg) accumulation, and especially monomethylmer- cury (MeHg) is acknowledged to be a significant and on-going health risk particularly in animals, including humans, which obtain a significant portion of their diet from fish (see Risher et al., 2002 for a review). While we have ample empirical evidence of the bioac- cumulative nature of MeHg from fish diets (see review by Clarkson and Magos, 2006; Burgess and Hobson, 2006; Hinck et al., 2009), we have much less pharmacokinetic data upon which to build pre- dictive models. Specifically we lack good quantitative information on the kinetics of uptake distribution and elimination of MeHg among important tissues, most importantly the transfer across the blood–brain barrier (BBB). Much of our understanding of the transfer of MeHg across the BBB comes from dosing studies of mammals (Jernelöv et al., 1976; Farris et al., 1993) with some limited data from humans exposed to extremely high doses (see review by Clarkson and Magos, 2006). ∗ Corresponding author at: School of the Environment, Trent University, Peter- borough, ON K9L 0G2, Canada. E-mail address: devans@trentu.ca (R.D. Evans). Indeed, most of the mammalian literature on brain uptake of MeHg involved doses that were unrepresentative of long-term low environmental exposure, which is arguably the more important scenario for most mammalian exposure. Most ingested MeHg is absorbed through the gastro-intestinal tract. MeHg is rapidly taken into the blood stream with approx- imately 90% associated with red blood cells (Kershaw et al., 1980). Transfer to the brain is thought to occur quickly thereafter (Warfvinge et al., 1992; Vahter et al., 1994). Transport across the BBB may be associated with a variety of water-soluble proteins or sulfhydryl-containing amino acids (Aschner and Aschner, 2007), particularly the MeHg–S–cysteine complex. Some evidence from long-term laboratory studies suggests conversion of MeHg to inor- ganic forms in the brain over time (e.g. Charleston et al., 1995; Pedersen et al., 1999), leading to an increase in the ratio of inorganic Hg (IHg) to MeHg with age. Presumably the changing ratio is a result of demethylation coupled with the limited ability of inorganic Hg to eliminate across the BBB. Generally, it is accepted that the long- term build-up of IHg in the brain carries the most risk to the functioning of the central nervous system (CNS; e.g. USEPA, 1997). Given the wide-spread distribution of Hg in the environment, mammals such as rats and monkeys used in pharmacokinetic stud- ies, commonly have some prior exposure to both MeHg and IHg. http://dx.doi.org/10.1016/j.etap.2016.01.007 1382-6689/© 2016 Elsevier B.V. All rights reserved.