Accumulation and tissue distribution of mercury in the guinea pig during subacute administration of methyl mercury

Abstract

Female guinea pigs were dosed po daily for 71 days with 0.4, 4, 40, or 400 μg Hg/kg given as radiolabeled methyl mercuric chloride. The accumulation of total mercury was followed in 10 tissues at 6 time intervals. After dosing ceased, the decay profiles of mercury were followed for an additional 35 days. The accumulation pattern for mercury was similar for each dose level, and the tissue mercury concentration on day 71 increased in the following order: blood < cerebellum < hypothalamus < calcarine cortex < frontal lobe < occipital lobe < caudate nucleus < muscle < liver < kidney. Mercury accumulation in all tissues, except kidney at the 4-, 40-, and 400-μg/kg dose levels, approached steady-state values in the 35–71 -day dosing period. The accumulation curves could be fitted by an exponential equation incorporating the mercury half-life obtained from the decay profiles. As the dose level increased, tissue mercury concentrations increased to a greater extent than anticipated. Although doses increased 1000-fold from 0.4 to 400 μg Hg/kg, kidney concentrations increased 3300-fold after 71 days of dosing. At this time, inorganic mercury (Hg 2+) comprised 42% of the total kidney mercury and 5% of the total liver mercury at the 400 μg/kg dose. Clinical signs of methyl mercury intoxication were induced in guinea pigs after dosing daily for 9 days at 5 mg Hg/kg. The activities of 6 enzymes were monitored and cholinesterase (serum), choline acetylase (caudate nucleus) and carboxylesterase (liver) were significantly lower than control values. The total mercury concentration in whole brain was 28 μg/g (wet weight). Animals dosed at 400 μg Hg/kg for 71 days showed no decrease in the activities of the selected enzymes, there was no change in weight gain when compared to the control and there were no signs of methyl mercury toxicity. The highest brain mercury concentration after 71 days dosing was 11 μg/g (wet weight) in the caudate nucleus.