Sexual differences in the distribution and retention of organic and inorganic mercury in methyl mercury-treated rats

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At 56 days of age, male and female Long-Evans rats received 1 mumole of 203Hg-labeled methyl mercuric chloride per kilogram sc and total, organic, and inorganic mercury contents and concentrations in tissues were determined for up to 98 days postdosing. Whole body clearance of mercury was faster in females than in males, and females attained higher peak percentages of the methyl mercury dose in kidney and brain than did males. Females had significantly higher mean percentages of the mercury dose present in the kidney and brain as organic or total mercury and in brain as inorganic mercury than did males. Males had significantly higher mean percentages of the dose present as organic or total mercury in pelt and whole body than did females. When expressed on a concentration basis, the only significant sexual difference was in the higher average concentration of organic mercury in the kidneys of females. When expressed on a tissue content basis, significant male-female differences in the kinetics (sex X time interactions) of organic mercury retention were found in kidney, brain, skeletal muscle, pelt, and whole body. Significant sex X time interactions in the concentrations of organic mercury were found in kidney, skeletal muscle, and whole body. Kinetics of retention and concentration of inorganic Hg in the pelt differed significantly for males and females. Discordance in degree of statistical significance of differences in mercury contents and concentrations reflected in part differences in relative body composition of males and females. Integrated exposures of tissues of males and females to organic or inorganic mercury were determined by fitting multiexponential retention functions to retention data. Differences in integrated exposure were estimated by the female-to-male ratio of areas under retention curves. Reconstruction of whole body organic and inorganic mercury burdens from constituent tissues indicated that integrated exposures of males and females to inorganic mercury were equal but females had a lower integrated exposure to organic mercury. Integrated exposure of liver to either form of mercury was about equal in males and females. However, the integrated exposure of the brain of females to inorganic mercury was 2.19 times that of males suggesting a sexual difference in accumulation or retention of inorganic mercury in the nervous system. These sexual differences in distribution and retention of organic and inorganic mercury after methyl mercury exposure may underlie reported sexual differences in sensitivity to the toxic effects of methyl mercury.