The Risk Assessment Information System

Toxicity Profiles

Condensed Toxicity Summary for MANGANESE

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

July 1995

Prepared by A. A. Francis and C. Forsyth, Chemical Hazard Evaluation Group, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee


*Managed by Lockheed Martin Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400

Manganese is an essential trace element in humans that can elicit a variety of serious toxic responses upon prolonged exposure to elevated concentrations either orally or by inhalation. The central nervous system is the primary target. Initial symptoms are headache, insomnia, disorientation, anxiety, lethargy, and memory loss. These symptoms progress with continued exposure and eventually include motor disturbances, tremors, and difficulty in walking, symptoms similar to those seen with Parkinsonism. These motor difficulties are often irreversible. Based on human epidemiological studies, 0.8 mg/kg/day for drinking water exposure and 0.34 mg/m3 in air for inhalation exposure have been estimated as lowest-observed-adverse-effect levels (LOAELs) for central nervous system effects.

Effects on reproduction (decreased fertility, impotence) have been observed in humans with inhalation exposure and in animals with oral exposure at the same or similar doses that initiate the central nervous system effects. An increased incidence of coughs, colds, dyspnea during exercise, bronchitis, and altered lung ventilatory parameters have also been seen in humans and animals with inhalation exposure. A possible effect on the immune system may account for some of these respiratory symptoms.

Because of the greater bioavailability of manganese from water, separate reference doses (RfD) for water and diet were calculated. A chronic (EPA 1995) and subchronic RfD (EPA 1994) for drinking water of 0.005 mg/kg/day has been calculated by EPA from a human noobservedadverse-effect level (NOAEL) of 0.005 mg/kg/day; the NOAEL was determined from an epidemiological study of human populations exposed for a lifetime to manganese concentrations in drinking water ranging from 3.6-2300 µg/L (Kondakis et al. 1989). A chronic (EPA 1995) and subchronic RfD (EPA 1994) of 0.14 mg/kg/day for dietary exposure has been calculated by EPA from a human NOAEL of 0.14 mg/kg/day, which was determined from a series of epidemiological studies (Schroeder et al. 1966, WHO 1973, NRC 1989). Large populations with different concentrations of manganese in their diets were examined. No adverse effects that were attributable to manganese were seen in any of these groups. For both the drinking water and dietary values, the RfD was derived from these studies without uncertainty factors since manganese is essential in human nutrition and the exposure of the most sensitive groups was included in the populations examined. EPA (1995) indicates that the chronic RfD values are pending change.

A reference concentration (RfC) of 0.05 µg/m3 (EPA 1995) for chronic inhalation exposure was calculated from a human LOAEL of 0.05 mg/m3 for impairment of neurobehavioral function from an epidemiological study by Roels et al. (1992). The study population was occupationally exposed to airborne manganese dust with a median concentration of 0.948 mg/m3 for 0.2 to 17.7 years with a mean duration of 5.3 years. Neurological examinations, psychomotor tests, lung function tests, blood tests, and urine tests were used to determine the possible effects of exposure. The LOAEL was derived from an occupational-lifetime integrated respirable dust concentration of manganese dioxide expressed as mg manganese/m3 × years. Confidence in the inhalation RfC is rated medium by the EPA.

Some conflicting data exist on possible carcinogenesis following injections of manganese chloride and manganese sulfate in mice. However, the EPA weight-of-evidence classification is: D, not classifiable as to human carcinogenicity based on no evidence in humans and inadequate evidence in animals (EPA 1995). Retrieve Toxicity Profiles Formal Version

Last Updated 8/29/97

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