Perinatal and lifetime exposure to methylmercury in the mouse: Blood and brain concentrations of mercury to 26 months of age

Chronic, low-level exposures to environmental toxicants, because they often begin prenatally and then persist throughout the individual's lifetime, po se challenging issues to risk assessment. Exposure to low levels of methylm ercury through the diet, based largely on consumption of fish and sea mamma ls, 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 c hallenge the functional capacities of the individual. Aging, with its dimin ished functional capacities and compensatory reserves provides such a chall enge, but, to explore this possibility, requires basic information about bl ood and brain levels under conditions of chronic lifetime exposure. The cur rent research was undertaken to provide such information. One hundred femal e B6C3F(1)/HSD mice were assigned to one of three dose groups, 0. 1, or 3 p pm 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 x CBA/J HSD. Dosing of the females began 4 weeks pr ior to breeding and continued for the two methylmercury-exposed groups thro ughout 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 absorptio n. 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 grea ter extent in the perinatal groups. Blood levels in the I ppm lifetime grou p remained unchanged between months 14 and 26, but brain levels rose modest ly. In the 3 ppm lifetime group, both brain and blood levels rose significa ntly between months 14 and 26, suggesting an interaction between dose and a ge. (C) 2001 Published by Elsevier Science Inc.