Perinatal and Lifetime Exposure to Methylmercury in the Mouse: Blood and Brain Concentrations of Mercury to 26 Months of Age

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Chronic, low-level exposures to environmental toxicants, because they often begin prenatally and then persist throughout the individual’s lifetime, pose challenging issues to risk assessment. Exposure to low levels of methylmercury through the diet, based largely on consumption of fish and sea mammals, follows this pattern. Early development is considered to be a period of heightened vulnerability during which even low-level exposures may produce undetected, “silent”, damage that is revealed only under conditions that challenge the functional capacities of the individual. Aging, with its diminished functional capacities and compensatory reserves provides such a challenge, but, to explore this possibility, requires basic information about blood and brain levels under conditions of chronic lifetime exposure. The current research was undertaken to provide such information. One hundred female B6C3F 1/HSD mice were assigned to one of three dose groups, 0, 1, or 3 ppm methylmercury chloride administered in a 5 nM sodium carbonate drinking solution. They were bred with male CBA/J HSD mice to produce the trihybrid offspring B6C3F 1/ HSD× CBA/J HSD. Dosing of the females began 4 weeks prior to breeding and continued for the two methylmercury-exposed groups throughout breeding and gestation. The methylmercury-treated litters were split into two subgroups, one exposed throughout its lifetime (set at 26 months) to the original dose, the other exposed through postnatal day 13 (PND 13). Brain and blood concentrations were assayed by cold-vapor atomic absorption. Samples were obtained on PND 4 and 21, and then at the end of months 14 and 26. On PND 4, brain and blood levels closely reflected maternal dosing. In all groups, concentrations fell sharply from PND 4 to 21, but to a greater extent in the perinatal groups. Blood levels in the 1 ppm lifetime group remained unchanged between months 14 and 26, but brain levels rose modestly. In the 3 ppm lifetime group, both brain and blood levels rose significantly between months 14 and 26, suggesting an interaction between dose and age.