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Biochemical and morphological studies of monkeys chronically exposed to methylmercury
Abstract:
This study was designed to correlated autopsy findings with the effects on cage behavior, laboratory values, and mercury clearance of long-term, low-dose exposure of primates to methylmercury. Six rhesus monkeys were given daily methylmercury hydroxide (MeHg) orally in apple juice on a preplanned dosage schedule. Three were sacrificed while receiving MeHg (group I) and the other 3 were sacrificed 2-5 mo after cessation of MeHg administration (group II). Whole-blood Hg levels (organic and inorganic) were assayed weekly, and major organ levels were assayed at autopsy. Whole-blood Hg levels were maintained between 1 and 2 micrograms/ml when the monkeys were given a MeHg dose of 80-125 micrograms/kg . d for up to 1 yr. The Hg burden of the major organs appeared to be dose- and duration-related. After periods of clearance (2.5-5 mo), intestinal wall Hg burden decreased to less than 1 microgram/g, and the hepatic Hg burden was still between 1.12 and 2.37 micrograms/g. However, the kidneys had a higher concentration of Hg, ranging from 10.34 to 29.54 micrograms/g. Whenever there was a high concentration of Hg, significant ultrastructural changes were observed. In the kidneys there were intracytoplasmic vacuoles and electron-dense inclusion bodies. In the small intestine of the animals cleared of mercury (group II), there were normal Paneth cells, as well as some degenerative cells characterized by dilation of endoplasmic reticulum and the presence of intracellular inclusion bodies. These findings suggest the long turnover time of Hg in these cell populations. During the period of study, weekly routine laboratory data including hematology, blood chemistry, and liver and kidney function tests did not reveal any significant changes.
Insights
Long-term, low-dose methylmercury (MeHg) exposure in primates led to significant mercury accumulation in kidneys and intestines. Despite clearance periods, ultrastructural changes persisted, indicating a long turnover time for mercury in these tissues.
Area of Science:
- Toxicology
- Primate Research
- Environmental Health
Background:
- Methylmercury (MeHg) is a neurotoxin with potential long-term health effects.
- Understanding mercury accumulation and clearance in biological tissues is crucial for risk assessment.
Purpose of the Study:
- To correlate autopsy findings with cage behavior, laboratory values, and mercury clearance after long-term, low-dose methylmercury exposure in primates.
- To investigate the dose- and duration-dependent effects of methylmercury on organ mercury burden and ultrastructure.
Main Methods:
- Six rhesus monkeys were administered methylmercury hydroxide (MeHg) orally for up to one year.
- Three monkeys were sacrificed during exposure (Group I), and three after a 2.5-5 month clearance period (Group II).
- Whole-blood mercury levels were monitored weekly; organ mercury burden and ultrastructural changes were assessed at autopsy.
Main Results:
- Mercury levels in major organs were dose- and duration-dependent.
- Kidneys showed the highest mercury concentration (10.34–29.54 µg/g) with significant ultrastructural changes, including intracytoplasmic vacuoles.
- Intestinal wall mercury burden decreased after clearance, but hepatic burden remained elevated (1.12–2.37 µg/g), with observed degenerative changes in intestinal cells.
Conclusions:
- Kidneys and intestines exhibit prolonged mercury retention and accumulate significant levels even after cessation of exposure.
- Ultrastructural changes in these organs suggest a long turnover time for mercury in kidney and intestinal cell populations.
- Routine laboratory tests did not reveal significant changes, highlighting the importance of autopsy and ultrastructural analysis for detecting low-dose mercury toxicity.