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The clearance of manganese chloride in the primate
1Division of Toxicology and Environmental Health Sciences Center, University of Rochester Medical Center, New York 14642.
Abstract:
Two macaque monkeys inhaled trace amounts of 54MnCl2 for 30 min. Subsequently the chest, head, and fecal radioactivity were monitored for over a year. The chest data curve required a sum of three exponential terms, with half-times ranging from 0.2 to 187 days, to attain a satisfactory fit. Head levels peaked 40 days after acute inhalation exposure and remained elevated for over a year. The excretion of manganese through the feces was best described by a sum of two exponentials. One had a half-time of less than 1 day and the second had a half-time of 50 to 60 days. A third macaque received a 6-week continuous exposure to 54Mn through a subcutaneous osmotic pump. With this route, manganese clearance from the head occurred at a faster rate than after acute inhalation exposure. Fecal elimination following continuous subcutaneous exposure resembled that following acute inhalation. Kinetic analyses suggested that the long half-times of manganese in the head following inhalation reflected both slow disappearance from the head and replenishment from other depots.
Insights
Manganese-54 inhalation in macaques showed prolonged retention in the head, with slow clearance and replenishment. Fecal excretion revealed distinct short and long elimination phases.
Area of Science:
- Environmental Toxicology
- Radioactive Isotope Kinetics
- Primate Physiology
Background:
- Understanding the toxicokinetics of inhaled radioactive metals is crucial for risk assessment.
- Manganese (Mn) is an essential element, but excessive exposure can lead to neurological deficits.
- Radioactive isotopes like Manganese-54 (54Mn) are used to study Mn metabolism and distribution.
Purpose of the Study:
- To investigate the absorption, distribution, and excretion kinetics of inhaled Manganese-54 (54Mn) in macaques.
- To determine the long-term retention and clearance rates of 54Mn in different tissues, particularly the head.
- To compare the toxicokinetics of acute inhalation exposure versus continuous subcutaneous exposure to 54Mn.
Main Methods:
- Two macaques inhaled trace amounts of 54MnCl2 for 30 minutes.
- Radioactivity in the chest, head, and feces was monitored for over a year post-inhalation.
- A third macaque received continuous 54Mn exposure via a subcutaneous osmotic pump for six weeks.
Main Results:
- Chest radioactivity decay required a sum of three exponential terms with half-lives from 0.2 to 187 days.
- Head 54Mn levels peaked at 40 days post-inhalation and remained elevated for over a year.
- Fecal excretion followed two exponential phases: one with a half-life <1 day and another with a 50-60 day half-life.
- Subcutaneous 54Mn exposure led to faster head clearance compared to inhalation.
- Fecal elimination patterns were similar for both exposure routes.
Conclusions:
- Inhaled 54Mn exhibits prolonged retention in the macaque head, influenced by slow disappearance and potential replenishment from other body depots.
- The kinetic data suggest complex distribution and elimination pathways for inhaled manganese.
- Continuous subcutaneous exposure offers a different kinetic profile for head manganese clearance compared to acute inhalation.