Health Effects Support Document for Manganese 2 Health Effects Support Document for Manganese Prepared for:

U. S. Environmental Protection Agency Office of Water ( 4304T) Health and Ecological Criteria Division Washington, DC 20460 www. epa. gov/ safewater/ ccl/ pdf/ manganese. pdf EPA 822 R 03 003 February 2003 iii Manganese   February 2003 FOREWORD The Safe Drinking Water Act ( SDWA), as amended in 1996, requires the Administrator of the Environmental Protection Agency to establish a list of contaminants to aid the agency in regulatory priority setting for the drinking water program. In addition, SDWA requires EPA to make regulatory determinations for no fewer than five contaminants by August 2001. The criteria used to determine whether or not to regulate a chemical on the CCL are the following:

The contaminant may have an adverse effect on the health of persons.

The contaminant is known to occur, or there is a substantial likelihood that the contaminant will occur, in public water systems with a frequency and at levels of public health concern.

In the sole judgment of the administrator, regulation of such contaminant presents a meaningful opportunity for health risk reduction for persons served by public water systems.

The Agency's findings for all three criteria are used in making a determination to regulate a contaminant. The Agency may determine that there is no need for regulation when a contaminant fails to meet one of the criteria. The decision not to regulate is considered a final agency action and is subject to judicial review.

This document provides the health effects basis for the regulatory determination for manganese. In arriving at the regulatory determination, data on toxicokinetics, human exposure, acute and chronic toxicity to animals and humans, epidemiology, and mechanisms of toxicity were evaluated. In order to avoid wasteful duplication of effort, information from the following risk assessments by the EPA and other government agencies were used in development of this document:

U. S. EPA 1994a. U. S. Environmental Protection Agency. Drinking Water Criteria Document for Manganese. Office of Health and Environmental Assessment, Cincinnati, OH CEAO CIN D008, prepared September, 1993, revised March 31, 1994.

ATSDR. 2000. Agency for Toxic Substances and Disease Registry. Toxicological Profile for Manganese ( Update). Department of Health and Human Services. Atlanta, GA. Available at http:// www. atsdr. cdc. gov.

U. S. EPA 1996a. U. S. Environmental Protection Agency. Integrated Risk Information System ( IRIS): Manganese. Available at http:// www. epa. gov/ iris. Last revised December 1, 1996.

In addition, primary references of studies published in peer reviewed scientific journals relevant to human risk assessment of manganese were also used in preparing this Drinking Water iv Manganese   February 2003 Support Document for Manganese. Recent studies of manganese were identified by literature searches conducted in 1999 and 2000.

Generally a Reference Dose ( RfD) is provided as the assessment of long term toxic effects other than carcinogenicity. RfD determination assumes that thresholds exist for certain toxic effects such as cellular necrosis. It is expressed in terms of milligrams per kilogram per day ( mg/ kg day). In general, the RfD is an estimate ( with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population ( including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.

The carcinogenicity assessment for manganese includes a formal hazard identification. Hazard identification is a weight of evidence judgment of the likelihood that the agent is a human carcinogen via the oral route.

Guidelines that were used in the development of this assessment may include the following: the Guidelines for Carcinogen Risk Assessment ( U. S. EPA, 1986a), Guidelines for the Health Risk Assessment of Chemical Mixtures ( U. S. EPA, 1986b), Guidelines for Mutagenicity Risk Assessment ( U. S. EPA, 1986c), Guidelines for Developmental Toxicity Risk Assessment ( U. S. EPA, 1991a), Proposed Guidelines for Carcinogen Risk Assessment ( 1996b, 1999b), Guidelines for Reproductive Toxicity Risk Assessment ( U. S. EPA, 1996c), and Guidelines for Neurotoxicity Risk Assessment ( U. S. EPA, 1998a); Recommendations for and Documentation of Biological Values for Use in Risk Assessment ( U. S. EPA, 1988); and Health Effects Testing Guidelines ( OPTS series 870, 1996 drafts; U. S. EPA 40 CAR Part 798, 1997); Peer Review and Peer Involvement at the U. S. Environmental Protection Agency ( U. S. EPA, 1994b); Use of the Benchmark Dose Approach in Health Risk Assessment ( U. S. EPA, 1995).

The chapter on occurrence and exposure to manganese through potable water was developed by the Office of Ground Water and Drinking Water. It is based primarily on unregulated contaminant monitoring ( UCM) data collected under SDWA. The UCM data are supplemented with ambient water data as well as information on production, use, and discharge. v Manganese   February 2003 ACKNOWLEDGMENTS This document was prepared under the U. S. EPA contract No. 68 C 02 009, Work Assignment No. B 02 with ICF Consulting, Fairfax, Virginia. The Lead U. S. EPA Scientist is Julie Du, Ph. D., Health and Ecological Criteria Division, Office of Science and Technology, Office of Water. vi Manganese   February 2003 TABLE OF CONTENTS FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii ACKNOWLEDGMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v LIST OF TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1.0 EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 2.0 IDENTITY: CHEMICAL AND PHYSICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . 2 1 3.0 USES AND ENVIRONMENTAL FATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 3.1 Production and Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 3.2 Sources and Environmental Fate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4 4.0 EXPOSURE FROM DRINKING WATER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1 4.2 Ambient Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1 4.3 Drinking Water Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 4 4.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 10 4.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 11 5.0 EXPOSURE FROM ENVIRONMENTAL MEDIA OTHER THAN WATER . . . . . . . . . 5 1 5.1 Food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1 5.1.1 Concentrations of Manganese in Food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1 5.1.2 Intake of Manganese From Food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1 5.2 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5 5.2.1 Concentration of Manganese in Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5 5.2.2 Intake of Manganese in Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 11 5.3 Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 12 5.3.1 Concentration of Manganese in Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 12 5.3.2 Intake of Manganese in Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 12 5.4 Other Media . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 12 5.5 Summary of Exposure to Manganese in Media Other Than Water . . . . . . . . . . . . . . . 5 12 6.0 TOXICOKINETICS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1 6.1 Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1 6.2 Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 7 6.3 Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 11 6.4 Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 12 7.0 HAZARD IDENTIFICATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1 7.1 Human Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1 7.1.1 Case Reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1 vii Manganese   February 2003 7.1.2 Short term Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 3 7.1.3 Long Term and Epidemiological Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 4 7.1.4 Beneficial Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 9 7.2 Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 10 7.2.1 Acute Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 10 7.2.2 Short Term Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 12 7.2.3 Subchronic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 14 7.2.4 Neurotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 16 7.2.5 Developmental/ Reproductive Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 25 7.2.6 Chronic Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 33 7.2.7 Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 34 7.3 Other Key Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 37 7.3.1 Mutagenicity/ Genotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 37 7.3.2 Immunotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 41 7.3.3 Hormonal Disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 41 7.3.4 Physiological or Mechanistic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 42 7.3.5 Structure Activity Relationship . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 45 7.4 Hazard Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 45 7.4.1 Synthesis and Evaluation of Major Noncancer Effects . . . . . . . . . . . . . . . . . . 7 45 7.4.2 Synthesis and Evaluation of Carcinogenic Effects . . . . . . . . . . . . . . . . . . . . . 7 48 7.4.3 Mode of Action and Implications in Cancer Assessment . . . . . . . . . . . . . . . . 7 49 7.4.4 Weight of Evidence Evaluation for Carcinogenicity . . . . . . . . . . . . . . . . . . . . 7 50 7.4.5 Sensitive Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 50 7.4.6 Potential Childhood Sensitivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 50 7.4.7 Other Potentially Sensitive Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 52 8.0 DOSE RESPONSE ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1 8.1 Dose Response for Noncancer Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1 8.1.1 RfD Determination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1 8.1.2 RfC Determination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3 8.2 Dose Response for Cancer Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 4 9.0 RISK DETERMINATION AND CHARACTERIZATION OF RISK FROM DRINKING WATER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1 9.1 Regulatory Determination for Chemicals on the CCL . . . . . . . . . . . . . . . . . . . . 9 1 9.1.1 Criteria for Regulatory Determination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1 9.1.2 National Drinking Water Advisory Council Recommendations . . . . . . . . . . . . 9 2 9.2 Health Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2 9.2.1 Health Criterion Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3 9.2.2 Hazard Characterization and Mode of Action Implications . . . . . . . . . . . . . . . 9 3 9.2.3 Dose Response Characterization and Implications in Risk Assessment . . . . . 9 5 9.3 Occurrence in Public Water Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 6 9.3.1 Occurrence Criterion Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 6 9.3.2 Monitoring Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 7 9.3.3 Use and Fate Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 8 viii Manganese   February 2003 9.4 Risk Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 9 9.4.1 Risk Reduction Criterion Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 9 9.4.2 Exposed Population Estimates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 9 9.4.3 Relative Source Contribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 10 9.4.4 Sensitive Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 10 9.5 Regulatory Determination Decision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 11 10.0 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 1 APPENDIX A: Abbreviations and Acronyms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A 1 APPENDIX B: Complete NIRS Data for Manganese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B 1 ix Manganese   February 2003 LIST OF TABLES Table 2 1. Chemical and Physical Properties of Manganese. . . . . . . . . . . . . . . . . . . . . . . . 2 2 Table 2 2. Chemical and Physical Properties of Manganese Compounds. . . . . . . . . . . . . . 2 3 Table 3 1. Imports of Manganese and Ferromanganese to the United States ( thousand metric tons, gross weight). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 Table 3 2. Manganese Manufacturers and Processors by State. . . . . . . . . . . . . . . . . . . . . . 3 2 Table 3 3. Summary of Uses for Selected Manganese Compounds. . . . . . . . . . . . . . . . . . 3 3 Table 3 4. Environmental Releases ( in pounds) for Manganese in the United States, 1988   1998. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 6 Table 3 5. Environmental Releases ( in pounds) for Manganese Compounds in the United States, 1988   1998. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 7 Table 4 1. Manganese Detections and Concentrations in Streams and Ground Water. . . . 4 5 Table 4 2. Manganese Detections and Concentrations in Bed Sediments and Aquatic Biota Tissues ( all sites). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 5 Table 4 3. Manganese Occurrence in Ground Water PWS of NIRS Survey. . . . . . . . . . . . 4 8 Table 4 4. Occurrence Summary of Ground and Surface Water Systems by State for Manganese. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 9 Table 5 1. Manganese Concentrations in Selected Foods . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2 Table 5 2. Average Concentrations of Manganese in Ambient Air Sampled from 1953   1982 5 6 Table 5 3. Manganese Levels in Air of Canadian Urban Locations as Determined by Personal Exposure Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 6 Table 5 4. Ambient Air Concentrations of Manganese in Relation to Traffic Density, Montreal, Canada 1981   1994. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 8 Table 5 5. Estimated Atmospheric Mn Concentration in Relation to the Combustion of MMT in Gasoline. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 9 Table 5 6. Mean Manganese Exposures from 3 day Indoor, Outdoor and Personal Air Samples. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 10 Table 5 7. Summary of Human Exposure to Manganese in Media Other than Water . . . 5 13 Table 6 1. Normal Manganese Levels in Human and Animal Tissues . . . . . . . . . . . . . . . . 6 8 Table 7 1. Mean Neurological Scores of Residents in Three Areas of Northwest Greece . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 5 Table 7 2. Mean Neurological Scores of Residents in Germany Exposed to Different Levels of Manganese in Well Water. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 8 x Manganese   February 2003 Table 7 3. LD 50 Values for Manganese Compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 11 Table 7 4. Neurological Effects of Oral Exposure to Manganese . . . . . . . . . . . . . . . . . . . 7 17 Table 7 5. Developmental Effects of Exposure to Manganese. . . . . . . . . . . . . . . . . . . . . 7 26 Table 7 6. Reproductive Effects of Exposure to Manganese. . . . . . . . . . . . . . . . . . . . . . . 7 32 Table 7 7. Follicular Cell Tumor Incidence in B6C3F 1 Mice. . . . . . . . . . . . . . . . . . . . . . 7 35 Table 7 8. Summary of Carcinogenicity Studies Reporting Positive Findings for Selected Manganese Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 35 Table 7 9. Pulmonary Tumors in Strain A Mice Treated with Manganese Sulfate . . . . . 7 36 Table 7 10. Genotoxicity of Manganese In Vivo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 37 Table 7 11. Genotoxicity of Manganese In Vitro. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 39 Table 9 1. Comparison of Average Daily Intake from Drinking Water and Other Media . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 10 1 1 Manganese   February 2003 1.0 EXECUTIVE SUMMARY The U. S. Environmental Protection Agency ( EPA) has prepared this Health Effects Support Document to assist in determining whether to establish a National Primary Drinking Water Regulation ( NPDWR) for manganese. At high doses by inhalation, manganese is very toxic, as seen by occupational exposure in miners. On the other hand, manganese is essential for normal physiological function of animals and humans. The Food and Nutrition Board of the National Academy of Science ( NAS) sets an adequate intake for manganese at 2.3 mg/ day for men and 1.8 mg/ day for women, and an upper limit for daily intake at 11 mg for adults ( IOM, 2002). Manganese has a low aesthetic threshold in water. Based on staining and taste, EPA has set a secondary level for manganese at 0.05 mg/ L which is below the level that may present a health concern. Available data suggest that regulation of manganese in public water does not present a meaningful basis for health risk reduction. EPA will present a determination and further analysis in the Federal Register Notice covering the Contaminant Candidate List proposals.

Manganese ( Chemical Abstracts Services Registry Number 7439 96 5) is an abundant elemental metal that does not exist naturally in its pure form, but rather is found as a component of over 100 minerals. It is also an essential nutrient, and a certain level of intake is necessary for good health. The NAS has determined that the Adequate Intake for manganese ( AI) is 1.8 to 2.3 milligrams per day for an adult woman and man, respectively, although others have argued that it may be higher. Manganese occurs naturally in soil, air, water, and food at low levels.

Manganese and manganese compounds are used mostly in the production of manganeseiron alloy through a smelting process. They are also used in fertilizer, fungicide, livestock feed, and in unleaded gasoline as an anti knock additive in the form of methylcyclopentadienyl manganese tricarbonyl ( MMT). Any of these uses may result in substantial releases of manganese to the environment. Manganese is listed as a Toxic Release Inventory ( TRI) chemical, with releases to soil constituting most of the on site releases, although air, surface water and ground water are also important sinks for manganese release.

Human exposure to manganese occurs primarily through ingestion of foods containing manganese. These include many nuts, grains, fruits, legumes, tea, leafy vegetables, infant formulas, and some meat and fish. The relatively high levels of manganese in nuts, grains, and many plant products and infant formulas are not well absorbed upon ingestion because these foods also contain inhibitors of manganese absorption such as phytates, fiber, plant protein and polyphenolic compounds ( tannins). Manganese absorption is affected by other factors including age ( neonate compared to the adult), chemical species of manganese, dose, and route of exposure in addition to the dietary factors mentioned above. Human exposure to manganese may also occur through inhalation of manganese dust, intake of soil containing manganese compounds, or drinking water contaminated with manganese.

The primary target of manganese toxicity is the nervous system, and common symptoms of toxic exposure include ataxia, dementia, anxiety, a " mask like" face, and manganism, a syndrome similar to Parkinson's disease. These effects, when observed, are generally the result 1 2 Manganese   February 2003 of very high exposures via inhalation, as might occur in an industrial setting, and are not seen among the general population exposed to low or moderate manganese levels. Manganese has very low toxicity by oral ingestion and reports of adverse effects by this route are rare. Because manganese is an essential nutrient, concern for toxic over exposure must be balanced against the potentially negative effects of nutritional deficiency resulting from under exposure.

An epidemiological study performed in Peloponnesus, Greece ( Kondakis et al., 1989) showed that lifetime consumption of drinking water containing naturally high concentrations of manganese oxides may lead to neurological symptoms and increased manganese retention ( through the concentration of manganese in hair) for people over 50 years old. For the group consuming the highest concentration ( around 2 mg/ L) for more than ten years, the authors suggested that some neurologic impairment may be apparent. The study raises concerns about possible adverse neurological effects following chronic ingestion from drinking water at doses within ranges deemed essential. However, the study did not examine manganese intake data from other routes/ sources ( i. e., dietary intake, inhalation from air, etc.), precluding its use as a basis for the RfD.

Another long term drinking water study in Germany ( Vieregge et al., 1995) found no neurological effects in people older than 50 years of age who drink water containing 0.3 to 2.16 mg/ L of manganese for more than ten years. However, this study also lacks exposure data from other routes and sources, and the manganese concentration range in water is very wide. Thus, the study cannot be used for quantitative assessment.

A small Japanese community ( total 25 individuals) ingested high levels of manganese in contaminated well water ( that leaked from dry cell batteries buried near the wells) over a threemonth period ( Kawamura et al., 1941). Manganese intake was not determined at the time of intoxication, but when assayed months later, it was estimated to be close to 29 mg/ L ( i. e., 58 mg/ day or approximately 1 mg/ kg day assuming a body weight of 60 kg). Symptoms included lethargy, increased muscle tonus, tremor, mental disturbances, and even death. Autopsies revealed macroscopic and microscopic changes in the brain tissue. In contrast, six children ( 1 to 10 yr old) were not intoxicated as were the adults by this exposure. The elderly were more severely affected. Some effects may have resulted from factors other than manganese exposure.

There is no information available on the carcinogenic effects of manganese in humans, and animal studies have reported mixed results. Based on the 1999 Draft Guidelines for Carcinogen Risk Assessment, there is " Inadequate Information to Assess Human Carcinogenic Potential" for manganese ( U. S. EPA, 1999b). According to the 1986 Guidelines, EPA considered manganese to be not classifiable with respect to carcinogenicity, Group D ( U. S. EPA, 1986b). Data from oral exposure suggest that manganese has a low developmental toxicity.

In various surveys, manganese intakes of adults eating western type and vegetarian diets ranged from 0.7 to 10.9 mg per day ( Freeland Graves, 1994; Gibson, 1994 as cited by IOM, 2002). Depending on individual diets, a normal intake may be well over 10 mg per day, especially from a vegetarian diet ( Schroeder et al., 1966). Thus, from the dietary surveys taken together, EPA concludes that an appropriate reference dose ( RfD) for manganese is 10 mg/ day 1 3 Manganese   February 2003 ( 0.14 mg/ kg day, U. S. EPA, 1996a). This RfD is unique, with an uncertainty factor ( UF) of 1 applied to a human chronic NOAEL of 0.14 mg/ kg day. The UF of 1 is used because the NOAEL ( with no apparent LOAEL) is based on chronic human dietary intake surveys, not the typical toxicity studies, and because of the essentiality of the trace element.

EPA derived a health related benchmark for evaluating the occurrence data, called the health reference level ( HRL), of 0.30 mg/ L. The HRL is six times the s MCL of 0.05 mg/ L. The HRL is based on the dietary RfD and application of a modifying factor ( MF) of three for drinking water as recommended by IRIS ( U. S. EPA, 1996a), and on an allocation of an assumed 20% relative source contribution from water ingestion as opposed to total manganese exposure. The modifying factor accounts for concerns raised by the Kondakis study ( 1989), the potential for higher absorption of manganese in water compared to food, consideration of fasting individuals, the concern for infants with potentially higher absorption and lower excretion rates of manganese, and the potential for increased susceptibility to neurotoxic effects of ingested manganese as compared to adults. For example, Dorman et al. ( 2000) reported that rat pups dosed for 21 days postnatally with 11 or 22 mg Mn/ kg day ( by mouth in drinking water) exhibited significant increases in the startle response compared to controls. Significant increases in striatal DA ( dopamine) and DOPAC ( dihydroxyphenylacetic acid) concentrations, in the absence of pathological lesions, were also observed in the high dose treated neonates. Because manganese is an essential nutrient in developing infants, the potential adverse effects from manganese deficiency may be of greater concern than potential toxicity from over exposure. Potentially sensitive sub populations include children, the elderly, pregnant women, irondeficient individuals, and individuals with impaired liver function.

Exposure to manganese in drinking water is ubiquitous in the United States. Data from the National Inorganics and Radionuclide Survey ( NIRS), conducted between 1984 and 1986 by EPA, were used to characterize manganese occurrence in public water systems ( PWSs). Although somewhat out of date, these data indicate that occurrence estimates are relatively high, with approximately 68% of ground water PWSs ( an estimate of approximately 40,000 systems nationally) showing detections of manganese, affecting about 55% of the ground water PWS population served ( approximately 47.5 million people nationally). The median levels for detects and the 99th percentile concentration for all samples were 0.01 milligram per liter ( mg/ L) and 0.63 mg/ L, respectively. Based on this survey information ( which consisted only of ground water and not surface water sampling), and using supplemental surface water levels from Safe Drinking Water Act ( SDWA) compliance monitoring data from five States, EPA concluded that population exposure to manganese in PWSs is potentially high.

When the detected concentrations are evaluated at a draft health reference level ( HRL) of 0.3 mg/ L, approximately 6.1% of the NIRS PWSs have detections > ½ HRL (> 0.15 mg/ L), consisting of about 3,600 ground water PWSs nationally, and affecting approximately 4.6% of the population served ( estimated at four million people nationally). The percentage of NIRS PWSs with detections > HRL of 0.3 mg/ L is approximately 3.2% ( about 1,920 ground water PWSs nationally), affecting 2.6% of the population served ( estimated at approximately 2.3 million people nationally). It is important to note, however, that when average daily drinking 1 4 Manganese   February 2003 water intakes for manganese are compared with intakes from a normal diet, drinking water accounts for a relatively small proportion of total manganese intake. 2 1 Manganese   February 2003 2.0 IDENTITY: CHEMICAL AND PHYSICAL PROPERTIES Manganese is an abundant element which makes up about 0.1% of the earth's crust ( ATSDR, 2000). Although the elemental ( metal) form of manganese does not occur naturally in the environment, manganese is a component of over 100 minerals ( ATSDR, 2000). The most common mineral forms include manganese dioxide, manganese carbonate, and manganese silicate ( ATSDR, 2000). Manganese exists in 11 oxidative states, with the most common valences being 2+, 4+, and 7+ ( U. S. EPA, 1994a). Although there is no recommended daily allowance ( RDA) for manganese, it is essential for the proper function of several enzymes and is necessary for normal bone structure and brain function ( U. S. EPA, 1994a). The chemical and physical properties of elemental manganese are presented in Table 2 1. Chemical and physical properties for manganese compounds are summarized in Table 2 2. 2 2 Manganese   February 2003 Table 2 1. Chemical and Physical Properties of Manganese.

Property Information Chemical Abstracts Services ( CAS) Registry No. 7439 96 5 Chemical Formula Mn Atomic Number 25 Molecular Weight 54.94 Synonyms Elemental manganese; Colloidal manganese; Cutaval; Magnacat; Tronamang NIOSH Registry of Toxic Effects of Chemical Substances ( RTECS) No. 009275000 Hazardous Substances Data Bank ( HSDB) No. 00550 Boiling Point 1,962oC Melting Point 1,244oC Vapor Pressure ( at 1,292oC) 1 mm Hg Density ( at 20oC) 7.21   7.44 g/ cm3 Water Solubility Decomposes Acid Solubility Dissolves in dilute mineral acids Sources: ATSDR ( 2000); U. S. EPA ( 1994a); ChemIDplus ( 2000) 2 3 Manganese   February 2003 Table 2 2. Chemical and Physical Properties of Manganese Compounds.

Name CAS Registry No. Synonyms Valence Chemical Formula Molec.

Wt. Specific Gravity or Density Melting Point ( oC) Boiling Point ( oC) Soluble in Water?

Methylcyclopentadienyl manganese tricarbonyl ( MMT) 12108 13 3 Pi methylcyclopentadienylmanganese tricarbonyl; Tricarbonyl( methylcyclopentadienyl)

manganese; Tricarbonyl( 2 methylcyclopentadienyl) manganese;

Tricarbonyl( eta( 5) methylcyclopentadienyl) manganese; Manganese,

tricarbonyl ( methyl pi cyclopentadienyl);

Manganese, tricarbonyl(( 1,2,3,4,5 eta) 1 methyl

2,4 cyclopentadien 1 yl); Manganese,

tricarbonyl( 2 methylcyclopentadienyl);

pi( Methylcyclopentadienyl) manganese tricarbonyl;

2 Methylcyclopentadienylmanganese tricarbonyl;

( Methylcyclopentadienyl) tricarbonylmanganese;

Methylcymantrene + 1 CH 3 C 5 H 4 Mn( CO) 3 218.09 1.39 1.5 233 No Manganous carbonate 598 62 9 Carbonic acid, manganese( 2+) salt;

Manganese( 2+) carbonate;

Manganese carbonate;

Manganese( II) carbonate;

Natural rhodochrosite + 2 MnCO 3 114.95 3.125 Decomposes NS Yes Manganous chloride 7773 27 01 5 Manganese chloride;

manganese dichloride;

manganese bichloride;

manganese( II) chloride + 2 MnCl 2 125.84 NS 650 1190 Yes Manganous acetate 15243 27 3  + 2 Mn( C 2 H 3 O 2) 2B4H 2 O 245.08 1.589 NS NS Yes; Cold H 2 O Table 2 2. Chemical and Physical Properties of Manganese Compounds. ( continued)

Name CAS Registry No. Synonyms Valence Chemical Formula Molec.

Wt. Specific Gravity or Density Melting Point ( oC) Boiling Point ( oC) Soluble in Water?

2 4 Manganese   February 2003 Manganous acetate 638 38 0 Acetic acid, manganese( II) salt;

Diacetyl manganese;

Manganese( 2+) acetate;

Manganese acetate;

Manganese diacetate;

Manganese( II) acetate;

Manganous acetate;

Octan manganaty + 2 Mn( C 2 H 3 O 2) 2 173.02 1.74 NS NS Decomposes Manganese ethylenebisdithiocarbamate 12427 38 2 Carbamic acid, ethylenebis( dithio, manganese salt; Carbamodithioic acid, 1,2 ethanediylbis,

manganese( 2+) salt;

1,2 Ethanediylbis( carbamodithioato) ( 2)

manganese;

Manganous ethylenebis( dithiocarbamate);

Maneb + 2 ( CH 2 NHCS 2) 2 Mn 265.24 NS NS NS Moderately Manganous oxide 1344 43 0 Manganese monoxide;

Manganese oxide;

Manganese protoxide + 2 MnO 70.94 5.43   5.46 1,945 NS No Manganous phosphate 10124 54 6 Manganese orthophosphate;

Phosphoric acid, manganese salt + 2 Mn 3( PO 4) 2 259.78 NS NS NS NS Manganous sulfate 7785 87 7 Manganese sulfate;

Sulfuric acid, manganese ( II) salt + 2 MnSO 4CH 2 O 169.01 2.95 Stable;

57   117 NS NS Manganous difluoride 7782 64 1 Manganese difluoride Manganese fluoride;

Manganese fluorure + 2 MnF 2 92.93 3.98 856 NS Yes Manganous trifluoride 7782 53 1  + 2 MnF 3 111.93 3.54 Decomposes 600 NS Decomposes Manganese borate 12228 91 0 Boron manganese oxide;

Tetraboron manganese heptaoxide + 2 MnB 4 O 7 C8H 2 O 354.17 NS NS NS No Table 2 2. Chemical and Physical Properties of Manganese Compounds. ( continued)

Name CAS Registry No. Synonyms Valence Chemical Formula Molec.

Wt. Specific Gravity or Density Melting Point ( oC) Boiling Point ( oC) Soluble in Water?

2 5 Manganese   February 2003 Manganese formate   NS Mn( CHO 2) 2C2H 2 O 181.00 1.953 Decomposes NS Yes Manganese glycerophosphate 1320 46 3 1,2,3 Propanetriol, mono( dihydrogen phosphate),

manganese( 2++) salt Glycerol, dihydrogen phosphate, manganese( 2+)

salt; Manganese( 2+) 1,2,3 propanetriol mono( dihydrogen phosphate); Manganese( 2+)

glycerol dihydrogen phosphate + 2 MnC 3 H 7 O 6 P 225.00 NS NS NS Slightly in Cold H 2 O Manganous hydroxide  Pyrochaotite + 2 Mn( OH) 2 88.95 3.258 ( 13 BC) Decomposes NS Slightly in Cold H 2 O Manganous nitrate 10377 66 9 Manganese dinitrate;

Nitric acid, manganese( 2+) salt + 2 Mn( NO 3) 2C4H 2 O 215.01 1.82 25.8 129.4 Yes Manganous sulfide   + 2 MnS 87.00 3.99 Decomposes NS Slightly in Cold H 2 O Manganese dioxide 1313 13 9 Manganese peroxide;

manganese binoxide;

manganese black;

battery manganese;

pyrolusite + 4 MnO 2 86.94 5.026 535 NS No Potassium permanganate 7722 64 7 Permangnaic acid;

potassium salt;

chameleon mineral + 7 KMnO 4 158.03 2.7 Decomposes 240 NS Yes Sources: ATSDR ( 2000); U. S. EPA ( 1994a); ChemIDplus ( 2000).

Log K ow and threshold information was not available for manganese compounds.

NS = Not Specified 3 1 Manganese   February 2003 3.0 USES AND ENVIRONMENTAL FATE The uses and environmental fate of manganese in air, water, and soil have been extensively reviewed by ATSDR ( 2000) and U. S. EPA ( 1994a). Information from these documents and other sources is summarized below.

3.1 Production and Uses Manganese is a naturally occurring element that constitutes approximately 0.1% of the earth's crust. It does not occur in the environment in its pure metal form, but is ubiquitous as a component of over 100 minerals, including many silicates, carbonates, sulfides, oxides, phosphates, and borates ( ATSDR, 2000). Manganese occurs naturally at low levels in soil, water, air, and food. Of the heavy metals, manganese is surpassed in abundance only by iron ( ATSDR, 2000).

In the United States, most manganese ore is smelted to produce ferromanganese, which is a manganese iron alloy ( ATSDR, 2000). The latter is used primarily in the production of steel to improve stiffness, hardness, and strength. The ore is mined in open pit or shallow underground mines, though little has been mined in the U. S. since 1978 ( ATSDR, 2000; USGS, 2000). Almost all of the manganese ore used in steel production in the United States is imported ( see Table 3 1; ATSDR, 2000). Large quantities of ferromanganese are imported as well ( USGS, 2000). Table 3 2 provides further information by State of the widespread manufacture and processing of manganese.

Table 3 1. Imports of Manganese and Ferromanganese to the United States ( thousand metric tons, gross weight).

Compound 1984 1988 1995 1996 1997 1998 1999 ^

manganese ore 308 499 394 478 355 332 535 ferromanganese 330 449 310 374 304 339 325 years 1984 and 1988: ATSDR, ( 1997) years 1995 to 1999: USGS, ( 2000) ^ estimated Manganese compounds are produced through reactions of various elements and compounds with either manganese ores or ferromanganese ( ATSDR, 2000). Some common manganese compounds include manganese chloride, manganese sulfate, manganese ( II, III) oxide, manganese dioxide, and potassium permanganate ( ATSDR, 2000). Uses of these compounds are varied, implying widespread environmental release. Significantly, approximately 80% of the potassium permanganate used in the United States is expended in wastewater and drinking water treatment ( U. S. EPA, 1984). Manganese dioxide is used in the production of matches, dry cell batteries, fireworks, and as a precursor for other manganese compounds. Manganese chloride is also used as a precursor for manganese compounds. A large proportion ( 60%) of U. S. manganese sulfate is used as a fertilizer, while the remainder is used in varnish, 3 2 Manganese   February 2003 Table 3 2. Manganese Manufacturers and Processors by State.

Statea Number of facilities Range of maximum amounts on site in thousands of Activities and usesc AL 60 0 50,000 1,2,3,6,7,8,9,12 AR 29 0 50,000 1,2,3,5,7,8,9,12,13 AZ 8 1 1,000 1,4,5,7,8,9,10,12 CA 55 0 500,000 1,2,3,4,5,6,7,8,9,10,11,12,13 CO 14 1 10,000 2,3,4,9,12 CT 16 1 1,000 2,3,9,10 DE 1 10 100 1,5,8 FL 26 0 10,, 000 8,9,10,13 GA 42 0 10,000 1,2,3,5,7,8,9,10,12,13 HI 1 10 100 9 IA 51 0 10,000 1,2,3,5,7,8,9,10,12 ID 3 1 1,000 9 IL 121 0 50,000 1,2,3,4,5,8,9,10,11,12,13 IN 161 0 50,000 1,2,3,4,5,6,7,8,9,10,11,12,13 KS 30 1 500,000 1,3,4,5,8,9,12,13 KY 63 0 500,000 1,2,3,4,5,6,7,8,9,10,12,13 LA 17 0 10,000 1,2,3,5,7,8,9,10,12,13 MA 26 0 1,000 1,2,3,4,5,9,10 MD 17 1 50,000 2,4,9,10,13 ME 8 1 100 1,3,9 MI 128 0 10,000 1,2,3,4,5,6,7,8,9,10,12,13 MN 28 0 10,000 8,9,10,12 MO 49 0 10,000 1,5,8,9,12 MS 23 0 50,000 8,9,13 MT 1 100,000 500,000 1,2,3,4,5,6,7 NC 57 0 10,000 1,2,3,5,8,9,10,11,12,13 ND 5 1 100 2,3,9 NE 18 0 10,000 1,2,3,8,9,12,13 NH 4 1 1,000 8,9 NJ 27 1 10,000 1,2,3,4,7,8,9,10 NM 1 10 100 9 NV 2 100 50,000 2,3,7 NY 63 0 10,000 1,2,3,4,5,7,8,9,10,12,13 OH 231 0 500,000 1,2,3,4,5,6,7,8,9,10,12,13 OK 48 0 10,000 1,2,3,4,5,6,8,9 OR 17 1 10,000 2,3,9,12,13 PA 179 0 100,000 1,2,3,4,5,7,8,9,10,11,12,13 PR 5 0 1,000 9 RI 5 1 1,000 2,3,9,10 SC 57 0 10,000 1,2,3,5,7,8,9,10,13 SD 7 1 100 9,13 TN 54 0 50,000 1,2,3,4,5,6,7,8,9,10,12,13 TX 85 0 10,000 1,2,3,4,5,6,8,9,10,12,13 UT 23 1 100,000 2,3,7,9,12,13 VA 23 0 1,000 1,3,5,7,8,9 VT 1 10 100 9 WA 27 0 1,000 1,2,3,6,8,9 WI 126 0 50,000 1,2,3,5,6,7,8,9,10,12,13 WV 15 1 500,000 8,9,10,13 WY 2 0 1,000 1,5 aPost office State abbreviations used bData in TRI are maximum amounts on site at each facility cActivities/ Uses 1. Produce 8. Formulation component 2. Import 9. Article component 3. On site use/ processing 10. Repackaging 4. Sale/ distribution 11. Chemical processing aid 5. Byproduct 12. Manufacturing aid 6. Impurity 13. Ancillary/ other uses 7. Reactant source: ATSDR ( 2000) compilation of 1996 TRI data fungicides, and as a livestock feed supplement. An organic manganese compound, methylcyclopentadienyl manganese tricarbonyl ( MMT), was used as an anti 3 3 Manganese   February 2003 knock additive in unleaded gasoline before it was banned in 1977. However, a 1995 court decision required EPA to reregister MMT and its use is ongoing ( ATSDR, 2000).

The uses of manganese compounds vary widely depending on the chemical form. Table 3 3 summarizes key uses of selected manganese compounds.

Table 3 3. Summary of Uses for Selected Manganese Compounds.

Compound Use Methylcyclopentadienyl manganese tricarbonyl ( MMT) Fuel additive Manganous carbonate Ferrites; animal feeds; ceramics; acid soluble manganese source Manganese chloride Catalyst in organic compound chlorination; trace mineral supply for animal feed; brick colorant; dye; drycell batteries; linseed oil drier; disinfecting; purifying natural gas Manganous acetate Mordant in dyeing; drying agent for paint and varnish; bister Manganese ethylenebisdithiocarbamate Agricultural fungicide Manganese oxide Ferrites; ceramics; fertilizer; livestock feed additive Manganese phosphate Ingredient of proprietary solutions for phosphating iron and steel Manganese sulfate Livestock feed additive; fertilizer; glazes; varnishes; ceramics; fungicides Manganous trifluoride Fluorinating agent in organic chemistry Manganese borate Drying agent for varnish and oil; linseed oil drier; leather industry Manganous nitrate Porcelain colorants; manufacture of reagent grade manganese dioxide Manganese dioxide ( electrolytic manganese, pyrolusite) Dry cell batteries; matches; fireworks; porcelain; glass bonding materials; amethyst glass; manufacturing manganese steel; oxidizer Potassium permanganate Oxidizing agent; water and air disinfectant; antialgal agent; metal cleaning, tanning, and bleaching agent; fresh flower and fruit preservative Sources: U. S. EPA ( 1994a); ATSDR ( 2000); Merck ( 1983). 3 4 Manganese   February 2003 3.2 Sources and Environmental Fate Manganese compounds are widely distributed in air, soil, and water. Sources of atmospheric manganese include industrial emissions, fossil fuel combustion, and erosion of manganese containing soils. Volcanic eruptions can also contribute to levels of manganese in air. Almost 80% of industrial emissions of manganese are attributable to iron and steel production facilities. Power plant and coke oven emissions contribute about 20%. Although soil erosion is considered an important source of atmospheric manganese, quantitative data for contributions from this source are not available. Due to generally low vapor pressure, manganese compounds in air exist primarily as suspended particulate matter. Because particle size is small, atmospheric manganese distribution can be widespread. These particles will eventually settle out via the process of dry deposition into surface waters or onto soils. Little information is available on the chemical reactions of atmospheric manganese, but it is expected to react with sulfur and nitrogen dioxide. The half life of manganese in air is only a few days ( ATSDR, 2000).

The fuel additive methylcyclopentadienyl manganese tricarbonyl ( MMT) is expected to contribute to urban air concentrations of manganese compounds. The fuel enhancing properties of MMT were first discovered in the 1950s, and the compound has been used as an additive in leaded and unleaded gasoline since the 1970s in the United States and Canada ( Lynam et al., 1999). MMT was banned for use in unleaded gasoline in the United States in 1977 in accordance with provisions in the Clean Air Act, which stated that all gasoline additives that were not " substantially similar" to gasoline were required to obtain a waiver proving that the additive did not " cause or contribute to the failure of emission control systems" ( Lynam et al., 1999). The U. S. EPA lifted this ban under court order in 1995, and MMT has been used freely since that time.

Gasoline without MMT contains virtually no manganese ( Lynam et al., 1999). The currently allowed maximum level of MMT in unleaded fuel is 0.03125 gram of manganese per U. S. gallon of gasoline ( 0.0083 g/ L or 10.4 ppm). The amount of manganese emitted from the tailpipe of an automobile using MMT containing fuel depends upon the type of engine, driving cycle, and age of the vehicle. Estimates for manganese in vehicular exhaust vary between 4% and 41% of the manganese consumed ( Ardeleanu et al., 1999). The remaining fraction apparently remains in the vehicle ( Ardeleanu et al., 1999). Early analysis of emissions suggested that manganese from combustion of MMT is emitted primarily as manganese tetroxide ( Mn 3 O 4) ( Ter Harr et al., 1975d as cited in Lynam et al., 1995). However, more recent testing suggests that when very low levels of MMT are combusted ( i. e., concentrations comparable to the currently allowed levels), manganese is emitted primarily as manganese phosphate and sulfate. The reported valence of the emitted manganese is + 2.2, with a mass median aerodynamic diameter of 1 to 2 microns ( Ethyl Corporation, 1997; Ressler et al., 1999; Wong et al., 1998; all as cited in Lynam et al., 1999). Uncombusted MMT rapidly decomposes to manganese oxide, carbon dioxide, and organic compounds in the atmosphere and has a half life of only a few seconds in the presence of sunlight ( Lynam et al., 1999; Zayed et al., 1999a). Data on the occurrence of manganese in air resulting from combustion of MMT and other sources are presented in Section 4.2. 3 5 Manganese   February 2003 Manganese is listed as a Toxic Release Inventory ( TRI) chemical. In 1986, the Emergency Planning and Community Right to Know Act ( EPCRA) established the TRI of hazardous chemicals. Created under the Superfund Amendments and Reauthorization Act ( SARA) of 1986, EPCRA is also sometimes known as SARA Title III. The EPCRA mandates that larger facilities publicly report when TRI chemicals are released into the environment. This public reporting is required for facilities with at least 10 full time employees that annually manufacture or process more than 25,000 pounds, or use more than 10,000 pounds, of TRI chemical ( U. S. EPA, 1996e, 2000a).

Under these conditions, facilities are required to report the pounds per year of manganese released into the environment both on and off site. The on site quantity is subdivided into air emissions, surface water discharges, underground injections, and releases to land ( see Table 3 4). For manganese, releases to land constitute most of the on site releases, with an abrupt decrease occurring in 1989. It is unclear whether this sharp decrease is real or a function of changes in TRI reporting requirements in the late 1980s and early 1990s ( see discussion below). Land releases have fluctuated modestly since that year with no trend evident. Air emissions are also an important mode of on site release. Though the first four years of record for air emissions are markedly higher, no trend is apparent for the remainder. Surface water discharges and underground injections are less significant on site releases, with underground injections sharply decreasing in 1994. Low levels of underground injection have continued to the present. Off site releases of manganese are considerable. Though in 1990 there was a large drop when compared to previous years, the late 1990s showed a steady increase in pounds released. These TRI data for manganese were reported from 49 States, excluding Alaska ( U. S. EPA, 2000b).

Only 1% of environmental manganese is released to water ( Table 3 4). The primary sources for surface and ground water releases are industrial facility effluent discharge, landfill and soil leaching, and underground injection. Manganese, in the form of potassium permanganate, may be used in drinking water treatment to oxidize and remove iron, manganese, and other contaminants ( ANSI/ NSF, 2000), in addition to its use in industrial wastewater purification and odor abatement ( ATSDR, 2000; U. S. EPA, 1984). Transport and partitioning of manganese in water is dependent on the solubility of the manganese form. The chemical form is controlled by factors such as pH, oxidation reduction potential ( Eh), and the available anions. Often, manganese in water will settle into suspended sediments. Little information is available on the biodegradation of manganese containing compounds in water, but factors such as pH and temperature are important for microbial activities. Data for occurrence of manganese in drinking water are presented in Section 4.3.

Approximately 91% of environmental manganese is released to soil. The main source of this release is land disposal of manganese containing wastes. The ability of manganese compounds to adsorb to soils and sediments is contingent upon the cation exchange capacity and organic content of the soil or sediment. Adsorption can vary widely based on differences in these two factors. Oxidative microbial activity may increase the precipitation of manganese minerals and increase the dissolution of manganese in subsurface environments. Occurrence data for manganese in soils are presented in Section 5.3. 3 6 Manganese   February 2003 TRI data are also available for the release of manganese compounds ( Table 3 5). Releases to land again constitute the largest proportion of on site releases. With the exception of 1997 and 1998, releases to land have generally decreased over the period of record. Air emissions are also an important mode of release and no trends are evident in the data. Significantly, surface water discharges and underground injections are much more substantial for the compounds than for elemental manganese, and have been generally increasing ( dramatically in some years) since the early 1990s. These data must be interpreted with caution, however, as they reflect changes in the requirements for reporting releases. In 1998, only releases of 75,000 lbs/ yr were required to be reported; this value is now 25,000 lbs/ yr. Therefore, although the values may seem to be increasing, they are likely comparable to past releases that were previously unreported. Further, the TRI data are meant to reflect releases and should not be used to estimate general exposure to a chemical ( U. S. EPA, 2000c, d).

Increases in surface water discharges and underground injections of manganese compounds have contributed to increases in total on and off site releases in recent years. The latter have returned to, or exceeded, the higher levels seen in the late 1980s and early 1990s. Off site releases, a large component of total releases, are also at their highest levels since reporting began in 1988. These TRI data for manganese compounds were reported from all 50 States ( U. S. EPA, 2000b).

Table 3 4. Environmental Releases ( in pounds) for Manganese in the United States, 1988   1998.

Year On Site Releases Off Site Releases Total On & Off Site Releases Air Emissions Surface Water Discharges Underground Injection Releases to Land 1998 970,658 260,403 3 9,995,895 15,967,545 27,194,504 1997 751,743 146,364 7 9,920,481 16,209,483 27,028,078 1996 816,733 117,571 8 10,111,563 15,191,636 26,237,511 1995 699,897 117,277 17 8,279,054 12,753,204 21,849,449 1994 818,600 89,332 10 8,452,582 14,076,682 23,437,206 1993 901,827 243,999 504 7,530,152 12,150,694 20,827,176 1992 721,047 235,307 304 6,543,600 11,997,270 19,497,528 1991 1,113,160 143,105 272 9,906,511 14,590,589 25,753,637 1990 1,168,809 139,358 881 9,031,215 11,364,721 21,704,984 1989 2,444,211 150,965 556 7,984,172 20,559,164 31,139,068 1988 1,586,675 321,993 255 20,229,826 20,087,660 42,226,409 source: U. S. EPA ( 2000b) 3 7 Manganese   February 2003 Table 3 5. Environmental Releases ( in pounds) for Manganese Compounds in the United States, 1988   1998.

Year On Site Releases Off Site Releases Total On & Off site Releases Air Emissions Surface Water Discharges Underground Injection Releases to Land 1998 1,566,352 4,471,582 7,755,610 52,820,578 45,269,882 111,884,004 1997 1,549,505 4,202,876 14,412,830 50,141,026 47,233,186 117,539,423 1996 1,828,684 2,119,241 15,630 40,334,426 33,543,677 77,841,658 1995 2,928,644 1,627,184 3,590 41,832,058 25,994,951 72,386,427 1994 3,060,424 857,825 5,930 38,228,464 25,840,954 67,993,597 1993 2,324,442 685,737 8,740 47,763,821 22,780,860 73,563,600 1992 2,079,044 733,728 22,569 63,490,137 17,297,544 83,623,022 1991 1,531,832 709,557 15,327 66,559,047 27,250,630 96,066,393 1990 2,276,084 721,787 2,842 83,331,787 35,789,554 122,122,054 1989 1,847,528 907,866 1,005,518 85,191,013 33,004,908 121,956,833 1988 1,801,463 681,469 6,816,070 84,227,842 20,670,921 114,197,765 source: U. S. EPA ( 2000b).

Although the TRI can be useful in giving a general idea of release trends, the data are far from exhaustive and have significant limitations. For example, only industries which meet TRI criteria ( at least 10 full time employees and manufacture and processing of quantities exceeding 25,000 lbs/ yr, or use of more than 10,000 lbs/ yr) are required to report releases. These reporting criteria do not account for releases from smaller industries. Threshold manufacture and processing quantities also changed from 1988 to 1990 ( dropping from 75,000 lbs/ yr in 1988 to 50,000 lbs/ yr in 1989 to its current 25,000 lbs/ yr in 1990), creating possibly misleading data trends. Finally, the TRI data are meant to reflect releases and should not be used to estimate general exposure to a chemical ( U. S. EPA, 2000c, d).

In summary, manganese and many of its compounds are naturally occurring and found at low levels in soil, water, air, and food. Furthermore, manganese compounds are produced in the United States from manganese ore and are in widespread use. Most ferromanganese is used in steel production, while other manganese compounds are used in a variety of applications from fertilizers and industrial products to water treatment. Recent statistics regarding import for consumption indicate production and use are substantial ( Table 3 1). Manganese and its compounds are also TRI chemicals ( Tables 3 4 and 3 5). Industrial releases have been reported since 1988 in all 50 States. Off site releases constitute a considerable amount of total releases, with releases to land being the most significant on site releases. 4 1 Manganese   February 2003 4.0 EXPOSURE FROM DRINKING WATER 4.1 Introduction This chapter examines the occurrence of manganese in drinking water. No complete national database exists regarding the occurrence of unregulated or regulated contaminants in drinking water from public water systems ( PWSs) collected under the Safe Drinking Water Act ( SDWA). In this chapter, existing federal and State data that have been screened for quality, completeness, and representativeness are aggregated and analyzed. Populations served by PWSs exposed to manganese are also estimated, and the occurrence data are examined for special trends. To augment the incomplete national drinking water data and aid in the evaluation of occurrence, information on the use and environmental release, as well as ambient occurrence of manganese, is also reviewed.

4.2 Ambient Occurrence To understand the presence of a chemical in the environment, an examination of ambient occurrence is useful. In a drinking water context, ambient water is source water existing in surface waters and aquifers before treatment. The most comprehensive and nationally consistent data describing ambient water quality in the United States are being produced through the United States Geological Survey's ( USGS) National Ambient Water Quality Assessment ( NAWQA) program. NAWQA, however, is a relatively young program and complete national data are not yet available from the entire array of sites across the nation.

Data Sources and Methods The USGS instituted the NAWQA program in 1991 to examine water quality status and trends in the United States. NAWQA is designed and implemented in such a manner to allow consistency and comparison among representative study basins located around the country, facilitating interpretation of natural and anthropogenic factors affecting water quality ( Leahy and Thompson, 1994).

The NAWQA program consists of 59 significant watersheds and aquifers referred to as " study units." The study units represent approximately two thirds of the overall water usage in the United States and a similar proportion of the population served by public water systems. Approximately one half of the nation's land area is represented ( Leahy and Thompson, 1994).

To facilitate management and make the program cost effective, approximately one third of the study units at a time engage in intensive assessment for a period of 3 to 5 years. This is followed by a period of less intensive research and monitoring that lasts between 5 and 7 years. This way, all 59 study units rotate through intensive assessment over a ten year period ( Leahy and Thompson, 1994). The first round of intensive monitoring ( 1991   96) targeted 20 watersheds and the second round monitored 16 basins beginning in 1994. 4 2 Manganese   February 2003 Manganese is an analyte for both surface and ground water NAWQA studies, with a Minimum Reporting Level ( MRL) of 0.001 mg/ L. Manganese occurrence in bed sediments and aquatic biota tissue is also assessed, with MRLs of 4 mg/ kg and 0.1 mg/ kg, respectively. Additional information on analytical methods used in the NAWQA study units, including minimum reporting levels, are described by Gilliom and others ( 1998).

Manganese data from the first two rounds of intensive NAWQA monitoring have undergone USGS quality assurance checks and are available to the public through their NAWQA Data Warehouse ( USGS, 2001). EPA has analyzed these data after further data quality review and occurrence results are presented below. The descriptive statistics generated from the manganese NAWQA data broadly characterize the frequency of manganese detections by sample and by site. Furthermore, detection frequencies above a Health Reference Level ( HRL) of 0.3 mg/ L are also presented for all samples, and by site. The HRL is a preliminary health effect level used for this analysis ( see Section 4.3 for further discussion of the HRL and its development). The median and 99th percentile concentrations are included as well to characterize the spread of manganese concentration values in ambient waters sampled by the NAWQA program.

Results Typical of many inorganic contaminants, manganese occurrence in ambient surface and ground waters is high ( Table 4 1). This is to be expected, considering that manganese constitutes approximately 0.1% of the earth's crust ( of the heavy metals, it is surpassed in abundance only by iron), and the element and its compounds are used in many products. Significantly, potassium permanganate is used in wastewater and drinking water treatment.

Detection frequencies are consistently greater for surface water than for ground water, possibly because surface waters are more likely to act as sinks for anthropogenic releases of manganese. Median concentrations are also generally higher for surface water ( median concentration for all sites is 0.016 mg/ L in surface water and 0.005 mg/ L in ground water). However, manganese detection frequencies > HRL are consistently higher in ground water, and 99th percentile ground water concentrations are as much as eight times larger than corresponding 99th percentile surface water concentrations. Locally high concentrations in ground water, higher than any seen in surface water, are not surprising given the possibility of long contact times between ground water and rocks enriched in manganese at a given location. Contact times between surface waters and naturally occurring manganese are orders of magnitude shorter, hence concentrations are lower. Furthermore, surface waters subject to large anthropogenic inputs of manganese are more easily diluted by waters integrated from other parts of the watershed, where manganese concentrations may be lower.

Table 4 1 illustrates that low level manganese occurrence is ubiquitous. Surface water detection frequencies by site are greater than 95% for all land use categories. Median concentrations and HRL exceedances ( by site) are greater in urban and agricultural basins compared to basins characterized as mixed land use or forest/ rangeland. This distribution of manganese occurrence is probably influenced by the wide use of manganese compounds in both industry and agriculture. Mixed land use basins are generally larger than either urban or 4 3 Manganese   February 2003 agricultural basins, and the lower occurrence in these basins may reflect some dilution of the contaminant. The 99th percentile concentrations for surface water range from 0.4 mg/ L to 0.8 mg/ L. The frequency of detections exceeding the MRL and HRL by site for all sites are approximately 96.9% and 10.2%, respectively. These figures indicate that, although manganese is nearly ubiquitous in surface water, detections at levels of public health concern are relatively low.

For ground water, detections by site are higher in urban and forest/ rangeland areas than in mixed or agricultural lands. Over 80% of urban and forest/ rangeland sites reported detections, while approximately 63 to 64% of mixed and agricultural land use sites detected manganese. The finding that ground water manganese occurrence is higher in forest/ rangeland areas than in either mixed or agricultural sites may result from natural variation in manganese occurrence in soil and rock. Urban areas have the highest median and 99th percentile concentrations ( 0.015 mg/ L and 5.6 mg/ L, respectively), as well as the highest detection frequencies ( by site: 85.3%) and HRL exceedances ( both by sample and by site: 17.2% and 21%, respectively) of manganese in groundwater. These results suggest that urban releases of manganese and manganese compounds can leach to ground water.

Detection frequencies and HRL exceedances by site for all ground water sites are approximately 70.1% and 13.8%, respectively. Again, these figures suggest that, while manganese occurrence in ground water is high, detections at levels of public health concern are relatively low.

Manganese was detected at 100% of NAWQA stream bed sediment sampling sites. The median and 99th percentile concentrations in bed sediments are 1.1 mg/ kg ( dry weight) and 9.4 mg/ kg ( dry weight), respectively. The occurrence of manganese in stream sediments is pertinent to drinking water concerns because, though many manganese compounds are either insoluble or have low solubility and are transported in water as suspended sediment, some desorption of the compound from sediments into water will occur through equilibrium reactions, although in very low concentrations.

In aquatic biota tissue, detections are also 100% of all samples and sites ( Table 4 2). However, concentration percentiles for tissues are substantially lower than for bed sediments: the median for biotic tissue is 0.01 mg/ kg ( dry weight) and the 99th percentile is 2.9 mg/ kg ( dry weight). Significant manganese concentrations in aquatic biota tissues would imply a potential for bioaccumulation. Although manganese was detected in aquatic biota tissues at 100% of samples and sites, low concentration percentiles suggest that the element does not bioaccumulate appreciably. 4 4 Manganese   February 2003 4.3 Drinking Water Occurrence National Inorganic and Radionuclide Survey ( NIRS)

In the mid 1980s, EPA designed and conducted the National Inorganic and Radionuclide Survey ( NIRS) to collect national occurrence data on a select set of radionuclides and inorganic chemicals being considered for National Primary Drinking Water Regulations. The NIRS database includes 36 inorganic compounds ( IOC) ( including 10 regulated IOCs), 2 regulated radionuclides, and 4 unregulated radionuclides. Manganese was one of the 36 IOCs monitored.

The NIRS provides contaminant occurrence data from 989 community PWSs served by ground water. The NIRS does not include surface water systems. The selection of this group of PWSs was designed so that the contaminant occurrence results are statistically representative of national occurrence. Most of the NIRS data are from smaller systems ( based on populationserved and each of these statistically randomly selected PWSs was sampled a single time between 1984 and 1986.

The NIRS data were collected from PWSs in 49 States. Data were not available for the State of Hawaii. In addition to being statistically representative of national occurrence, NIRS data are designed to be divisible into strata based on system size ( population served by the PWS). Uniform detection limits were employed, thus avoiding computational ( statistical) problems that sometimes result from multiple laboratory analytical detection limits. Therefore, the NIRS data can be used directly for national contaminant occurrence analyses with very few, if any, data quality, completeness, or representativeness issues.

Supplemental IOC Data One limitation of the NIRS study is a lack of occurrence data for surface water systems. To provide perspective on the occurrence of manganese in surface water PWSs relative to ground water PWSs, SDWA compliance monitoring data that were available to EPA were reviewed from States with occurrence data for both kinds of systems.

The State ground water and surface water PWS occurrence data for manganese used in this analysis were submitted by States for an independent review of the occurrence of regulated contaminants in PWSs at various times for different programs ( U. S. EPA, 1999a). In the U. S. EPA ( 1999a) review, occurrence data from a total of 14 States were noted. However, because several States contained data that were incomplete or unusable for various reasons, only 12 of the 14 States were used for a general overview analysis. From these 12 States, 8 were selected for use in a national analysis because they provided the best data quality and completeness and a balanced national cross section of occurrence data. These eight were Alabama, California, Illinois, Michigan, Montana, New Jersey, New Mexico, and Oregon. 4 5 Manganese   February 2003 Table 4 1. Manganese Detections and Concentrations in Streams and Ground Water.

Detection frequency > MRL* Detection frequency > HRL* Concentration percentiles ( all samples; mg/ L)

% samples % sites % samples % sites median 99th Surface Water urban 99.1 % 99.6 % 4.6 % 13.0 % 0.036 0.7 mixed 92.4 % 98.5 % 1.3 % 6.4 % 0.012 0.4 agricultural 96.3 % 97.2 % 3.7 % 12.3 % 0.019 0.7 forest/ rangeland 90.9 % 96.4 % 5.0 % 6.6 % 0.011 0.8 all sites 94.0 % 96.9 % 3.0 % 10.2 % 0.016 0.7 Ground Water urban 74.7 % 85.3 % 17.2 % 21.0 % 0.015 5.6 mixed 56.9 % 62.9 % 8.9 % 9.0 % 0.002 1.3 agricultural 61.4 % 64.0 % 11.9 % 12.8 % 0.004 1.6 forest/ rangeland 75.3 % 81.3 % 10.9 % 13.8 % 0.012 2.9 all sites 64.1 % 70.1 % 12.8 % 13.8 % 0.005 2.9 * The Minimum Reporting Level ( MRL) for manganese in water is 0.001 mg/ L and the Health Reference Level ( HRL) is 0.3 mg/ L. The HRL is a preliminary health effect level used for this investigation.

Table 4 2. Manganese Detections and Concentrations in Bed Sediments and Aquatic Biota Tissues ( all sites).

Detection frequency > MRL* Concentration percentiles ( all samples; mg/ kg dry weight)

% samples % sites median 99th sediments 100 % 100 % 1.1 9.4 aquatic biota tissues 100 % 100 % 0.01 2.9 * The Minimum Reporting Levels ( MRLs) for manganese in sediments and biota tissues are 4 µ g/ g and 0.1 µ g/ g, respectively. 4 6 Manganese   February 2003 Only the Alabama, California, Illinois, New Jersey, and Oregon State data sets contained occurrence data for manganese. The data represent more than 37,000 analytical results from about 4,000 PWSs mostly during the period from approximately 1993 to 1997, though some earlier data are also included. The number of sample results and PWSs vary by State.

Data Management The data used in the State analyses were limited to only those data with confirmed water source and sampling type information. Only standard SDWA compliance samples were used; " special" samples, " investigation" samples ( investigating a contaminant problem that would bias results), or samples of unknown type were not used in the analyses. Various quality control and review checks were made of the results, including follow up questions to the States providing the data. Many of the most intractable data quality problems encountered occurred with older data. These problematic data were, in some cases, simply eliminated from the analysis. For example, when the number of data with problems were insignificant relative to the total number of observations, they were dropped from the analysis ( for further details see U. S. EPA, 1999a).

Occurrence Analysis The summary descriptive statistics presented in Table 4 3 for manganese are derived from analysis of the NIRS data. Included are the total number of samples, the percent samples with detections, the 99th percentile concentration of all samples, the 99th percentile concentration of samples with detections, and the median concentration of samples with detections. The percentages of PWSs and population served indicate the proportion of PWSs and PWS population served whose analytical results showed a detection( s) of the contaminant ( simple detection, > MRL) at any time during the monitoring period; or a detection( s) greater than half the Health Reference Level ( HRL); or a detection( s) greater than the HRL. The HRL used for this analysis is 0.30 mg/ L.

The HRL was derived for contaminants not considered to be " linear" carcinogens by the oral route of exposure. EPA derived the HRL using an RfD approach as follows: HRL = ( RfD × 70 kg)/ 2 L × RSC,

where: RfD = Reference Dose; an estimated dose ( mg/ kg day) to the human population ( including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used;

70 kg = The assumed body weight of an adult;

2 L = The assumed daily water consumption of an adult; 4 7 Manganese   February 2003 RSC = The relative source contribution, or the level of exposure believed to result from drinking water when compared to other sources ( e. g., air), and is assumed to be 20% unless noted otherwise.

EPA used only the best available peer reviewed data and analyses in evaluating adverse health effects. Health effects information is available for manganese in the Integrated Risk Information System ( IRIS). IRIS is an electronic EPA data base containing reviewed information ( both inside and outside of the Agency) on human health effects that may result from exposure to various chemicals in the environment. These chemical files contain descriptive and quantitative information on RfDs for chronic noncarcinogenic health effects and hazard identification, as well as slope factors and unit risks for carcinogenic effects.

In Table 4 3, national occurrence is estimated by extrapolating the summary statistics for manganese to national numbers for systems, and population served by systems, from the Water Industry Baseline Handbook, Second Edition ( U. S. EPA, 2000e). From the handbook, the total number of ground water community water systems ( CWSs) plus ground water non transient, non community water systems ( NTNCWSs) is 59,440, and the total population served by ground water CWSs plus ground water NTNCWSs is 85,681,696 persons ( see Table 4 3). To arrive at the national occurrence estimate for the HRL, the national estimate for ground water PWSs ( or population served by ground water PWSs) is simply multiplied by the percentage for the given summary statistic [ i. e., the national estimate for the total number of ground water PWSs with detections at the HRL of 0.30 mg/ L ( 40,388) is the product of the percentage of ground water PWSs with detections ( 68%) and the national estimate for the total number of ground water PWSs ( 59,440)].

In Table 4 4, occurrence data on manganese directly submitted by the States of Alabama, California, Illinois, New Jersey, and Oregon for A Review of Contaminant Occurrence in Public Water Systems ( U. S. EPA, 1999a) were used to augment the NIRS study which lacked surface water data. Included in the table are the same summary statistics as shown in Table 4 3, with additional information describing the relative distribution of manganese occurrence between ground water and surface water PWSs in the 5 States.

The State data analysis was focused on occurrence at the system level because a PWS with a known contaminant problem usually has to sample more frequently than a PWS that has never detected the contaminant. The results of a simple computation of the percentage of samples with detections ( or other statistics) can be skewed by the more frequent sampling results reported by the contaminated site. The system level of analysis is conservative. For example, a system need only have a single sample with an analytical result greater than the MRL, i. e., a detection, to be counted as a system with a result " greater than the MRL."

When computing basic occurrence statistics, such as the number or percent of samples or systems with detections of a given contaminant, the value ( or concentration) of the MRL can have important consequences. For example, the lower the reporting limit, the greater the number of detections ( Ryker and Williamson, 1999). As a simplifying assumption, a value of half the MRL is often used as an estimate of the concentration of a contaminant in samples/ systems 4 8 Manganese   February 2003 Table 4 3. Manganese Occurrence in Ground Water PWS of NIRS Survey.

Frequency Factors Health Reference Level = 0.3 mg/ L National System & Population Numbers1 Total number of samples/ systems 989 59,440 99th percentile concentration ( all samples) 0.63 mg/ L

Minimum Reporting Level ( MRL) 0.001 mg/ L

99th percentile concentration of detections 0.72 mg/ L

Median concentration of detections 0.01 mg/ L

Total population 1,482,153 85,681,696 Occurrence by Samples/ System National Extrapolation HRL = 0.3 mg/ L Ground water PWSs with detections (> MRL) Range of sampled States 67.9% 8.3   100% 40,388 NA Ground water PWSs > ½ HRL Range of sampled States 6.1% 0   31.6% 3,606 NA Ground water PWSs > HRL Range of sampled States 3.2% 0   21.0% 1,923 NA Occurrence by Population Served Ground water PWS population served with detections Range of sampled States 55.4% 0.3   100% 47,502,000 NA Ground water PWS population served > ½ HRL Range of sampled States 4.6% 0   89.2% 3,940,000 NA Ground water PWS population served > HRL Range of sampled States 2.6% 0   89.2% 2,256,000 NA 1 Total PWS and population numbers are from EPA MRL = minimum reporting level HRL = health reference level March 2000 Water Industry Baseline Handbook. PWS = public water system   = no data NA = not applicable whose results are less than the MRL. However, for these occurrence data this is not straightforward. This is in part related to State data management differences as well as real differences in analytical methods, laboratories, and other factors.

The situation can cause confusion when examining descriptive statistics for occurrence. Because a simple meaningful summary statistic is not available to describe the various reported MRLs, and to avoid confusion, MRLs are not reported in the summary table ( Table 4 4). 4 9 Manganese   February 2003 Table 4 4. Occurrence Summary of Ground and Surface Water Systems by State for Manganese.

Frequency Factors Alabama California Illinois New Jersey Oregon Total number of samples Number of ground water samples Number of surface water samples 1,343 934 409 31,998 29,923 2,075 344 275 69 3,196 2,795 401 172 90 82 Percent samples with detections Percent ground water samples with detections Percent surface water samples with detections 30.2% 28.1%

35.0% 16.5% 17.5%

1.9% 44.2% 50.2%

20.3% 39.7% 40.6%

33.7% 39.5% 61.1%

15.9%

99th percentile concentration ( all samples) 0.13 mg/ L 0.71 mg/ L 0.96 mg/ L 0.42 mg/ L 1.6 mg/ L Minimum reporting level ( MRL) Variable1 Variable1 Variable1 Variable1 Variable1 99th percentile concentration of detections 0.56 mg/ L 1.52 mg/ L 57 mg/ L 0.89 mg/ L 6.7 mg/ L Median concentration of detections 0.02 mg/ L 0.15 mg/ L 0.04 mg/ L 0.02 mg/ L 0.05 mg/ L Total number of PWSs Number of ground water PWSs Number of surface water PWSs 434 365 69 2,516 2,293 223 227 160 67 1,179 1,147 32 84 54 30 Total population served Ground water population Surface water population 3,662,222 1,820,214 1,837,743 45,388,246 27,840,774 30,675,992 1,995,394 724,635 1,270,179 7,472,565 2,386,396 3,687,076 1,306,283 301,440 1,117,782 Occurrence by System PWSs with detections (> MRL) Ground water PWSs with detections Surface water PWSs with detections 46.5% 41.6% 72.5% 28.2% 29.8% 11.7% 41.4% 50.6% 19.4% 53.5% 52.3% 96.9% 46.4% 55.6% 30.0%

Health Reference Level ( HRL) = 0.3 mg/ L PWSs > ½ HRL Ground water PWSs > ½ HRL Surface water PWSs > ½ HRL 1.8% 1.4% 4.4% 17.2% 18.5% 3.6% 9.3% 11.9% 3.0% 5.8% 5.7% 9.4% 13.1% 20.4% 0.0%

PWSs > HRL Ground water PWSs > HRL Surface water PWSs > HRL 0.9% 0.6% 2.9% 10.1% 10.9% 1.8% 4.4% 5.0% 3.0% 2.5% 2.5% 3.1% 6.0% 9.3% 0.0%

Occurrence by Population Served PWS population served with detections Ground water PWS population with detections Surface water PWS population with detections 71.9%

50.9%

73.4% 49.3%

66.2%

10.5% 36.5%

66.3%

19.5% 85.7%

70.4%

100.0% 58.0%

41.8%

56.8%

Health Reference Level ( HRL) = 0.3 mg/ L PWS population > ½ HRL Ground water PWS population > ½ HRL Surface water PWS population > ½ HRL 5.9% 0.8%

0.7% 34.8% 52.6%

4.4% 16.5% 29.1%

9.4% 15.3% 10.4%

23.3% 4.6% 19.9%

0.0%

PWS population > HRL Ground water PWS population > HRL Surface water PWS population > HRL 2.4% 0.1% 0.6% 27.2% 42.8% 4.2% 14.7% 24.2% 9.4% 9.1% 4.9% 14.5% 3.2% 14.0% 0.0%

1 See text for details PWS = public water system MRL = minimum reporting level HRL = health reference level 4 10 Manganese   February 2003 The situation can cause confusion when examining descriptive statistics for occurrence. Because a simple meaningful summary statistic is not available to describe the various reported MRLs, and to avoid confusion, MRLs are not reported in the summary table ( Table 4 4).

Additional Drinking Water Data From 1996 AWWA Survey To augment the SDWA drinking water data analysis described above, results from a 1996 American Water Works Association ( AWWA) survey are reviewed. The survey, called WATER:/ STATS, is a cooperative project of AWWA and AWWA Research Foundation. The WATER:/ STATS survey database stores results from the 1996 WATER:/ STATS survey of water utilities in the United States and Canada in terms of facilities, scale of operation, and major inputs and outputs. A total of 794 AWWA member utilities responded to the survey with ground water and/ or surface water information. However, the actual number of respondents for each data category varies because not all participants in the survey responded to every question.

4.4 Results The NIRS data in Table 4 3 show that approximately 68% of ground water PWSs ( an estimate of approximately 40,000 systems nationally) had detections of manganese, affecting about 55% of the ground water PWS population served ( approximately 47.5 million people nationally). At an HRL of 0.30 mg/ L, approximately 6.1% of the NIRS PWSs had detections > ½ HRL ( about 3,600 ground water PWSs nationally), affecting approximately 4.6% of the population served ( estimated at 3.9 million people nationally). The percentage of NIRS PWSs with detections > HRL of 0.30 mg/ L was approximately 3.2% ( about 1,900 ground water PWSs nationally), affecting 2.6% of the population served ( estimated at approximately 2.3 million people nationally) ( Table 4 3).

Drinking water data for manganese from the supplemental individual States vary among States ( Table 4 4). Manganese has not been required for monitoring under SDWA, though these States had obviously conducted some monitoring. The number of systems with manganese data for Illinois and Oregon is far less than the number of PWSs in these States. Hence, the extent to which these data are representative is unclear. Alabama, California, and New Jersey have substantial amounts of data and PWSs represented. Because the NIRS data only represent manganese occurrence in ground water PWSs, the supplemental State data sets provide some perspective on surface water PWS occurrence. For example, the median concentration of detections for the States ranged from 0.02 mg/ L to 0.15 mg/ L, higher than the NIRS data ( 0.01 mg/ L). For detections by PWSs, 3 of the 5 States ( California, Illinois, and Oregon) had higher ground water PWS detections.

For simple detections, the supplemental State data show a range from 30% to 56% of ground water PWSs ( Table 4 4). These figures are lower than the NIRS ground water PWS results: 68% > MRL ( Table 4 3). The supplemental State data show considerably greater percentages of simple detections for surface water PWSs, with higher variability as well: 12%   97% > MRL. Comparisons made between data for simple detections need to be viewed 4 11 Manganese   February 2003 with caution because of differences in MRLs between the State data sets and the NIRS study, and among the States themselves ( see Section 4.3).

The supplemental State data sets indicate ground water PWS detections > HRL of 0.30 mg/ L between 0.6% and 11% ( Table 4 4). Again, this range brackets the NIRS national average of PWS > HRL of 0.30 mg/ L ( 3.2%) ( Table 4 4). Notably, surface water PWSs showed fewer exceedances of the HRL than ground water PWSs at this higher concentration; ranging from 0% to 3.1%.

Reviewing manganese occurrence by PWS population served shows that from 0.1%   43% of the States' ground water PWS populations were served by systems with detections > HRL of 0.30 mg/ L ( Table 4 4). Comparatively, 2.6% of the NIRS ground water PWS population served experienced detections > HRL of 0.30 mg/ L ( Table 4 3). Populations served by surface water PWSs with detections > HRL of 0.30 mg/ L ranged from 0%   14.5% among the five supplemental States. Population figures for the supplemental States are incomplete and are only reported for those systems in the database that have reported their population data. For manganese, approximately 80% of the PWSs reporting occurrence data for these 5 States also reported population data.

Occurrence in AWWA PWSs The AWWA sponsored 1996 WaterStats Survey showed manganese occurrence above levels at which health effects are expected to be realized to be relatively similar to that reported in the NIRS data and the supplemental State data. Approximately 11% of the participating ground water PWSs ( serving about 5.1 million people) had maximum detections of manganese in raw water greater than the HRL of 0.30 mg/ L. The 99th percentile of concentration and the median concentration were 9.0 mg/ L and 0.09 mg/ L, respectively. Surface water PWSs showed comparable results with approximately 12.8% of survey respondents ( serving about to 10.5 million people) having maximum detections of manganese in raw water greater than the HRL of 0.30 mg/ L. The 99th percentile of concentration and the median concentration in raw surface waters were 3.08 mg/ L and 0.092 mg/ L, respectively.

In finished ground water samples, approximately 3% of survey respondents ( serving close to 1.7 million people) had maximum detections of manganese greater than the HRL of 0.30 mg/ L. The 99th percentile concentration and the median concentration were 0.80 mg/ L and 0.021 mg/ L, respectively. For finished surface water samples, approximately 1.5% of survey respondents ( about 1.7 million people) reported maximum detections greater than the HRL of 0.30 mg/ L. The 99th percentile concentration and the median concentration in finished surface water samples were 0.64 mg/ L and 0.013 mg/ L, respectively.

4.5 Conclusion Manganese and its compounds are TRI chemicals. Industrial releases have been recorded since 1988 in all 50 States. Off site releases constitute a considerable amount of total releases, with releases to land being the most significant on site releases. 4 12 Manganese   February 2003 Low level manganese occurrence in ambient waters and bed sediments monitored by the USGS NAWQA program is ubiquitous, with detections approaching 100% of surface water sites and greater than 62% of ground water sites. Stream bed sediments and aquatic biota tissues show detections of 100% by sample and by site. Urban basins generally have more surface and ground water manganese detections greater than the HRL than basins in other land use categories, and higher median and 99th percentile concentrations. Although manganese detection frequencies are high in ambient waters, stream bed sediments, and aquatic biota tissue, manganese occurrence at levels of public health concern is low.

Manganese has been detected in ground water PWS samples collected through the NIRS study. Occurrence estimates are relatively high with approximately 68% of all samples showing detections affecting about 55% of the national population served. The 99th percentile concentration of all samples is 0.63 mg/ L. Exceedances of the HRL at 0.30 mg/ L affect 2.6% of the ground water PWS population served, or approximately 2.3 million people nationally.

Additional SDWA data from the States of Alabama, California, Illinois, New Jersey, and Oregon, including both ground water and surface water PWSs, were examined through independent analyses and also show substantial levels of manganese occurrence. These data provide perspective on the NIRS estimates that only include data for ground water systems. The supplemental State data show ground water systems reported higher manganese detections in 3 of the 5 States ( California, Illinois, and Oregon). If national data for surface water systems were available, the occurrence and exposure estimates would be substantially greater than from NIRS alone. 5 1 Manganese   February 2003 5.0 EXPOSURE FROM ENVIRONMENTAL MEDIA OTHER THAN WATER 5.1 Food 5.1.1 Concentrations of Manganese in Food Table 5 1 summarizes mean manganese concentrations in 234 foods analyzed by the Food and Drug Administration ( FDA). Nuts and grains contain the highest manganese concentrations, with values as high as 40 to 50 mg/ kg reported. Fruits, vegetables, fish, poultry, meat, and eggs tend to have intermediate concentrations. Manganese levels in milk tend to be low, with concentrations of 10 and 30 micrograms per liter (: g/ L) reported for human and cow's milk, respectively. In contrast, values of 50 to 300 : g/ L have been reported for infant formula ( Collipp et al., 1983).

Manganese has been detected in the muscle of fresh bluefin tuna ( Thunnus thynnus). Hellou et al. ( 1992) as reported in ATSDR ( 2000), analyzed concentrations in 14 tuna samples using inductively coupled plasma mass spectrometry. The level of manganese varied from 0.16 to 0.31 micrograms per gram (: g/ g) dry weight, with a mean value of 0.22 : g/ g dry weight.

Black tea samples from the United Kingdom ( UK) were found to have mean manganese concentrations of 4.6 mg/ L, 40% of which was bioavailable ( Powell et al., 1998).

The issue of bioavailability is important to consider when assessing manganese levels in foods, and is discussed further in the next section. For instance, the actual absorption of manganese from ingested tea is limited by the presence of polyphenolic compounds ( tannins) in the tea which bind manganese ( Freeland Graves and Llanes, 1994). This explains the low bioavailabilty of manganese in tea. Likewise, the relatively high levels of manganese in fruits, nuts, grains, and vegetables, as well as in soy based infant formula ( discussed in Section 5.1.2), are limited in their bioavailability by the presence of phytic acids, oxalic acids, and fiber in these foods ( U. S. EPA, 1996a). In addition, high levels of calcium or magnesium ingestion may inhibit manganese absorption, while persons with diets that are deficient in iron may experience increased manganese absorption ( U. S. EPA, 1996a).

5.1.2 Intake of Manganese From Food General Population Manganese is an essential nutrient. It is very unevenly distributed in foods. Although manganese is rich in tea, whole grains, legumes, and nuts, it is found in negligible amounts in meats, dairy products, sweets, refined grains, and most fruits. Thus, many individuals who do not consume whole grains, nuts, certain fruits ( pineapple), green leafy vegetables, and tea will consume a " low manganese" diet  less than 2 mg per day ( Davis et al., 1992). In addition, women tend to consume less food than men; hence their intakes of individual nutrients, including manganese, are often lower than those of men ( Pennington et al., 1989). 5 2 Manganese   February 2003 The Food and Nutrition Board set an adequate intake level ( AI) for manganese at 2.3 mg/ day for men and 1.8 mg/ day for women ( IOM, 2002; Trumbo et al., 2001). The current recommendations for infants and children are 0.003 to 0.6 mg/ day and 1.2 to 1.9 mg/ day, respectively ( IOM, 2002). An adequate intake level is defined as " a recommended intake value based on observed or experimentally determined approximations or estimates of nutrient intake by a group ( or groups) of healthy people that are assumed to be adequate  used when an RDA cannot be determined." Some nutritionists feel that this level may be too low. Freeland Graves et al. ( 1987), as cited in U. S. EPA ( 1996a), have suggested a range of 3.5 to 7 mg/ day for adults based on a review of human studies.

Dietary habits have evolved in recent years to include a larger proportion of meats and refined foods in conjunction with a lower intake of whole grains ( Freeland Graves, 1994; U. S. EPA, 1996a). The net result of such dietary changes includes a lower intake of manganese. A significant number of adult Americans, particularly women, may consume suboptimal amounts of manganese ( ATSDR, 2000; Pennington et al., 1986). On the other hand, it is not known whether infants may ingest more than the AI for their age group as a result of the high manganese content of prepared infant foods and formulas.

Table 5 1. Manganese Concentrations in Selected Foodsa TYPE OF FOOD RANGE OF MEAN CONCENTRATIONS ( mg/ kg)

Nuts and nut products 18.21   46.83 Grains and grain products 0.42   40.70 Legumes 2.24   6.73 Fruits 0.20   10.38 Fruit juices and drinks 0.05   11.47 Vegetables and vegetable products 0.42   6.64 Desserts 0.04   7.98 Infant foods 0.17   4.83 Meat, poultry, fish and eggs 0.10   3.99 Mixed dishes 0.69   2.98 Condiments, fats, and sweeteners 0.04   1.45 Beverages ( including tea) 0.00   2.09 Soups 0.19   0.65 Milk and milk products 0.02   0.49 a Adapted from ATSDR ( 2000) and Pennington et al. ( 1986). 5 3 Manganese   February 2003 Based on various surveys, the Food and Nutrition Board ( IOM, 2002) concluded that the average manganese intake of adults eating western type and vegetarian diets ranged from 0.7 to 10.9 mg/ day ( IOM, 2002), and the median intakes for women and men ranged from 1.6 to 2.3 mg/ day ( IOM, 2002). The total dietary manganese intake among individuals may vary greatly depending upon dietary habits. Individual intake estimates for Canadian adult male blue collar workers ( n = 28) and garage mechanics ( n = 37), as determined by analysis of dietary records, ranged from 1.0 to 14 mg/ day ( Loranger and Zayed, 1995). The mean values in this study for manganese intake by blue collar workers and mechanics were 3.7 and 2.9 mg/ day, respectively. It should be noted that FDA's Total Diet Study menus used to measure the levels of several nutritional elements including manganese from 1982 to 1986 in Pennington et al. ( 1989) reflect " typical" American diets and contain less manganese than the diets consumed by Canadian males.

The Food and Nutrition Board also set a tolerable upper intake level ( UI) for manganese at 11 mg per day for adults, based on the upper range of manganese intake for adults ( see review by Greger, 1999). An UI is defined as " the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects for almost all individuals in the general population. As intake increases above the UL, the risk of adverse effects may increase." For shorter duration, Davis and Greger ( 1992) reported that women given daily supplements of 15 mg manganese for 90 days experienced no adverse effects other than a significant increase in lymphocyte manganese dependent superoxide dismutase ( Greger, 1998, 1999; IOM, 2002).

Based on a conservative range for manganese intake of 2 to 10 mg/ day, U. S. EPA ( 1996a) estimated a dietary manganese intake of 28.6 to 126 micrograms per kilogram per day (: g/ kgday For children, assuming a manganese intake of 1.28 : g/ calorie ( U. S. EPA, 1984; ATSDR, 2000) and a caloric intake of 1,000 calories/ day for a 10 kg child, the estimated average daily intake would be 128 : g/ kg day.

Groups with Potential for High Manganese Intake from Food Groups with potential for high intake of dietary manganese include vegetarians, heavy tea drinkers, and infants. Vegetarians may consume a larger proportion of manganese rich nuts, grains, and legumes in their diet than the general population ( U. S. EPA, 1996a). Manganese intake by North American vegetarians has been estimated to be as high as 10 mg Mn/ day ( Gibson, 1994). However, many components of vegetarian diets, including phytates, tannins, oxalates, and fiber, inhibit manganese uptake from the gastrointestinal tract. Consequently, the bioavailability of manganese in vegetarian diets is uncertain. Johnson et al. ( 1991) studied the absorption of radiolabelled manganese from various plant foods in adult men and women, and reported that mean fractional absorption values from lettuce and spinach were 5.20 and 3.81%, respectively. Mean fractional absorption from sunflower seeds was significantly less ( 1.71%), while that from wheat was 2.16%. All percent absorption values from plant food were significantly less than mean values from MnCl 2 dissolved in water, which ranged from 7.74 to 10.24%. 5 4 Manganese   February 2003 Heavy tea drinkers may have a higher manganese intake than the general population. An average cup of tea may contain 0.4 to 1.3 mg manganese ( ATSDR, 2000). Consumption of three cups of tea per day would therefore have the potential to double manganese intake for some individuals. Again, however, it is likely that the high level of tannins in tea will result in reduced manganese absorption ( Freeland Graves and Llanes, 1994).

Infants may ingest high levels of manganese from infant formulas or prepared baby foods, although manganese absorption in infants is influenced by several variables, and the degree to which absorption levels may be a health concern is unknown. Infant formulas contain 50 to 300 : g/ L manganese ( Collipp et al., 1983), compared to human milk which contains 7 to 15 : g/ L manganese ( U. S. EPA, 1996a). Assuming an intake of 742 milliliters ( mL) of breast milk/ day ( U. S. EPA, 1996a), a breast fed infant would have an estimated daily manganese intake of 5.2 to 11.1 : g/ day. An infant consuming the same volume of infant formula would have an estimated daily manganese intake of 37.1 to 223 : g/ day. Assuming an average weight of 6 kg for an infant of age 6 months, the weight adjusted average daily intake would range from 0.87 to 1.85 : g/ kgday for breast fed infants. The corresponding weight adjusted intake for a formula fed infant would be 6.2 to 37.2 : g/ kg day. Generally, solid foods are introduced at the age of 4 months. Once solid foods are introduced, the dietary intake of manganese increases so substantially that the contribution of Mn intake from milk becomes less significant.

In assessing infant exposure to manganese, however, one must also consider constituents of infant formula and of breast milk which may affect manganese bioavailability. For instance, formula made from soy protein contains high levels of phytic acids and vegetable proteins which probably decrease the manganese bioavailability. If the formula is also iron fortified, manganese bioavailability may be further decreased, although studies on the inhibitory influences of iron have produced conflicting results ( Freeland Graves, 1994). Davidsson et al. ( 1989a) measured absorption of radiolabelled manganese in adult humans given human milk, cow's milk, or soy formula and found that fractional manganese absorption from human milk ( 8.2%) was significantly higher than absorption from cow's milk ( 2.4%) and soy formula ( 0.7%). Manganese in infant formula is in the divalent state, the absorption of which cannot be regulated by the lactoferrin receptors in the gut; breast milk manganese is in the trivalent form bound to lactoferrin, and its absorption is thus regulated ( U. S. EPA, 1996a). Davidsson et al. ( 1989a) suggested that the lactoferrin in human milk as well as the higher calcium content in cow's milk contributed to the difference in absorption. Dorner et al. ( 1989) observed similar differences in fractional manganese retention in infants as those observed by Davidsson et al. ( 1989a) in adults. In the infant study, a higher percentage of manganese was retained from ingested breast milk ( 41%) than from cow's milk formula (~ 19%). Therefore, many factors probably control manganese absorption from infant formula, and firm conclusions are difficult to make in the absence of more direct data. Keen et al. ( 1986) demonstrated that fractional manganese uptake from human breast milk and cow's milk were relatively high (~ 80% and ~ 89 %, respectively), whereas uptake from soy formula was lowest (~ 60%) in rat pups.

It should be noted that Davidsson et al. ( 1989a) performed their studies in adults; manganese body burden in infants may be additionally influenced by the fact that the biliary excretion system, which is the primary route of manganese excretion, is not completely 5 5 Manganese   February 2003 developed in neonates ( Lönnerdal, 1994). Studies in rats have further demonstrated that young animals absorb significantly more manganese in the gut than do mature animals ( Lönnerdal et al. 1987). Also, animal studies have shown that manganese crosses the blood brain barrier in neonates at a rate 4 times higher than that in adults ( Mena, 1974). However, the relevance of these studies to humans is unknown, and few direct absorption data for manganese in human infants are available. In this context, it is noteworthy that Collipp et al. ( 1983) reported hair manganese levels that increased significantly from birth ( 0.19 : g/ g) to 6 weeks ( 0.865 : g/ g) and 4 months ( 0.685 : g/ g) of age in infants given formula, while infants given breast milk exhibited no significant increase ( 0.330 : g/ g at 4 months). This study also reported that the average hair manganese level in children exhibiting learning disabilities was significantly increased ( 0.434 : g/ g) compared to those that exhibited normal learning ability ( 0.268 : g/ g).

5.2 Air 5.2.1 Concentration of Manganese in Air General Population Table 5 2 summarizes nationally aggregated data collected between 1953 and 1982 for manganese concentrations in ambient air of nonurban, urban, and source dominated locations. Average manganese concentrations for nonurban areas ranged from a high value of 60 nanograms per cubic meter ( ng/ m3) determined in 1953   1957 to a low of 5 ng/ m3 in 1982. Average concentrations for urban areas ranged from 110 to 33 ng/ m3 over the same period. Average levels in source dominated locations varied widely, ranging from a high reading of 8,300 ng/ m3 during the 1965   1967 measurement period, to concentrations of 130 to 140 ng/ m3 in 1982. Although differences in sample collection and analytical methods complicate interpretation, these data suggest that manganese concentrations in ambient air decreased over the time period of record ( U. S. EPA, 1984). This change has been attributed to installation of emissions controls in the metals industry ( ATSDR, 2000). More recently, U. S. EPA ( 1990) has proposed an average annual background concentration of 40 ng/ m3 for urban areas, based on data for 24 hour average concentrations in 102 cities across the U. S.

Multiple local studies have estimated airborne manganese concentrations. A series of Canadian studies evaluated total airborne manganese concentrations in the home and workplace ( Sierra et al., 1995; Zayed et al., 1994, 1996). Table 5 3 summarizes the results of these studies. Concentrations of manganese were determined by use of personal sampling devices. Mean levels of manganese measured in homes ranged from 7 to 12 ng/ m3. Mean workplace concentrations ranged from 12 to 44 ng/ m3 for non automotive workers ( primarily office workers) and taxi drivers. Automotive workers, such as auto mechanics, experienced mean workplace levels ranging from 250 to 448 ng/ m3. Sample sizes for these studies ranged from 9 to 35 individuals. 5 6 Manganese   February 2003 Table 5 2. Average Concentrations of Manganese in Ambient Air Sampled from 1953   1982a.

SAMPLING LOCATION/ YEAR CONCENTRATION ( ng/ m3)

1953   1957 1965   1967 1982 Nonurban 60 12 5 Urban 110 73 33 Source dominated No data 250   8,300 130   140 a Source: ATSDR ( 2000) and U. S. EPA ( 1984).

Table 5 3. Manganese Levels in Air of Canadian Urban Locations as Determined by Personal Exposure Monitoring.

OCCUPATION LOCATION DURATION N MEAN ( ng/ m3) RANGE ( ng/ m3) REFERENCE Garage worker Work 5 days 10 250 9   2,067 Zayed et al. ( 1994) Garage worker Home 2 days 10 7 4   27 Taxi driver Work 5 days 10 24 6   69 Taxi driver Home 2 days 10 11 4   22 Auto Mechanic Work 4 weeks 35 448 10   6,673 Sierra et al. ( 1995) Auto Mechanic Home 4 weeks 35 12 6   63 Nonautomotive Work 4 weeks 30 44 11   1,862 Nonautomotive Home 4 weeks 30 8 5   87 Office worker Work 7 days 23 12 2   44 Zayed et al. ( 1996) Taxi driver Work 7 days 9 28 8   73 5 7 Manganese   February 2003 Automotive fuels in Canada and the U. S. contain the antiknock agent methylcyclopentadienyl manganese tricarbonyl ( MMT). The allowable level of MMT in Canadian gasoline is 0.062 grams per gallon ( g/ gal), which is double the allowable limit of 0.031 g/ gal in the U. S. ( Davis et al, 1998). Combustion of MMT releases manganese to the atmosphere in the form of manganese oxides, phosphates, and sulfates ( see Section 3.2 above), and these compounds may constitute a significant source of manganese contamination in urban environments. In Canada, a car exhaust study determined that 4 to 41% of Mn in gasoline is emitted from the tailpipe, depending on the vehicle and driving cycle ( Ardeleanu et al., 1999). The fraction not emitted to the atmosphere appears to remain in the engine ( Ardeleanu et al., 1999).

Levels of unburned MMT in air resulting from emission of residual MMT in vehicular exhaust or evaporative emissions ( e. g., at gas stations) are expected to be low. Although data are limited, Zayed et al. ( 1999a) reported concentrations ranging from 0.4 ng/ m3 to 12 ng/ m3 when measured in five different microenvironments in Montreal, Canada. The highest average concentration of MMT in ambient air was measured at gas stations.

Use of MMT in gasoline has resulted in public health concerns related to the potential health effects of increased manganese exposure. As a result, determination of the extent to which MMT contributes to environmental levels of manganese ( and ultimately to human exposure) has been an area of active research. Several studies in Montreal, Canada have examined manganese concentrations in ambient air in relation to motor vehicle traffic ( Table 5 4). Loranger et al. ( 1994a) found ambient manganese concentrations to be significantly correlated with traffic density. Areas of intermediate and high traffic densities had ambient manganese concentrations above the natural background level in Montreal of 40 ng/ m3 ( Loranger and Zayed, 1994; Loranger et al., 1994a).

Loranger et al. ( 1995) summarized modeling and empirical data relating atmospheric manganese concentrations to combustion of gasoline containing varying concentrations of MMT ( Table 5 5). Estimated increases predicted by studies listed in the table but conducted prior to 1990 were characterized by Loranger et al. ( 1995) as being of limited use due to insufficient information on methodology. Based on an estimated background level of 40 ng/ m3 ( calculated by taking the average of data from 102 U. S. cities), U. S. EPA ( 1990) predicted that the potential increase in ambient background manganese from the use of MMT would be 0.05P, where P is the fraction of total manganese in fuel that is emitted in vehicular exhaust.

Canadian studies have addressed the fraction of total manganese concentration in air associated with particulates of respirable size. Zayed et al. ( 1996) reported respirable manganese ( MnR) and total manganese ( MnT) concentrations determined by personal exposure monitoring of taxi drivers and office workers. Mean concentrations of MnR were 10 and 15 ng/ m3 for office workers and taxi drivers, respectively. Mean concentrations of MnT were 12 and 28 ng/ m3 for the same respective groups. Loranger and Zayed ( 1997a) measured concentrations of MnR and MnT at two sites in Montreal with different vehicle traffic densities. MnR and MnT concentrations adjacent to a heavily traveled (> 100,000 vehicles/ day) road were 24 and 50 5 8 Manganese   February 2003 Table 5 4. Ambient Air Concentrations of Manganese in Relation to Traffic Density, Montreal, Canada 1981   1994.

TRAFFIC DENSITY ( vehicles/ day) Mn ( ng/ m3) REFERENCE < 15,000 < 40 ( 50% of samples) Loranger et al. ( 1994a)

> 15,000 > 40 ( 50% of samples) Loranger et al. ( 1994a)

4,900 26 Loranger et al. ( 1994b)

75,000 36 Loranger et al. ( 1994b)

< 15,000 20 Loranger and Zayed ( 1994)

< 30,000 50 Loranger and Zayed ( 1994)

> 100,000 60 Loranger and Zayed ( 1994)

117,585 54 Loranger et al. ( 1995)

117,585 29   37 Loranger et al. ( 1995)

Source: Zayed et al. ( 1999b)

ng/ m3, respectively. Values for MnR and MnT at a site with lower traffic density ( 10,000 to 15,000 vehicles/ day) were 15 and 27 ng/ m3, respectively. Zayed et al. ( 1999a) measured mean concentrations of respirable manganese ranging from 18 to 53 ng/ m3 in five microenvironments in Montreal. The overall mean concentrations of respirable and total manganese were 36 ± 7 ng/ m3 and 103 ± 32 ng/ m3, respectively. These data indicate that approximately 35 to 90% of total manganese in urban air is respirable.

Personal exposures ( expressed as concentration in air) to airborne manganese were measured before and after the introduction of MMT into 20% of the diesel fuel used in London ( Pfeifer et al., 1999). Concentrations of manganese encountered by office workers and taxi drivers ( 10 subjects/ occupation) were measured during 2 week periods in both 1995 ( before MMT introduction) and 1996 ( after MMT introduction). Manganese concentrations reported for office workers ranged from 2 to 239 ng/ m3 and from 4 to 147 ng/ m3 in 1995 and 1996, respectively. Taxi drivers experienced exposure to concentrations of 4 to 44 ng/ m3 and 9 to 36 ng/ m3 in 1995 and 1996, respectively. Thus, neither occupational group experienced apparent exposure to increased Mn after the introduction of MMT to gasoline. The greater exposure of office workers to airborne manganese when compared to taxi drivers was an unexpected result. The higher intake by office workers was attributed to manganese enrichment ( approximately 10 fold greater than in the general environment) of the particulate matter in subway tunnels. When 5 9 Manganese   February 2003 Table 5 5. Estimated Atmospheric Mn Concentration in Relation to the Combustion of MMT in Gasoline.

Mn concentration in gasoline Estimated concentration from MMT source ng/ m 3 Ambient air concentration from all sources ng/ m 3 Reference mg/ L g/ gal 132.0 0.5  200   800 ( Mena, 1974)

33.0 0.125 335 1,200   1,500a ( Piver, 1974)

33.0 0.125  2   250b ( Moran, 1975)

33.0 0.125  20   3,400c ( U. S. EPA, 1975)

33.0 0.125  70   720d ( U. S. EPA, 1975)

33.0 0.125  730   10,000e ( U. S. EPA, 1975)

33.0 0.125  120   3,630f ( U. S. EPA, 1975)

26.4 0.100 20   200g < 1,000h ( Ter Haal et al., 1975)

18.0 0.068 25i < 500h ( Cooper, 1984)

17.0 0.064 20   200  ( Abbott, 1987)

16.5 0.063 70   140 90   3,800j ( HWC, 1978)

16.5 0.063 20  ( Pierson et al., 1978)

8.3 0.031 17  ( Ethyl Corp., 1990)

8.3 0.031 150k 55l ( U. S. EPA, 1990)

8.3 0.031 10   20 50   60m ( U. S. EPA, 1991b)

10.0 0.038 < 1   3n 34 ( Loranger et al., 1995)

2   29o

Source: Table adapted from Loranger et al. ( 1995). a Annual average. b 24 hour average. c EPA model: 24 hour average; beside highway ( 1   500 m), 20% emission at the tailpipe. d Ethyl corp. model: 24 hour average, beside highway ( 1   500 m), 20% emission at the tailpipe. e EPA model: hourly peak, beside highway ( 1 500 m), 20% emission at the tailpipe. f Ethyl corp. model: hourly peak, beside highway ( 1 500 m), 20% emission at the tailpipe. g Median value = 0.05, near roadway. h Median value. I Beside highways. j Maximum monthly average. k 30% emission at the tailpipe, mid size car ( 20 mi/ US gal). l Urban annual average background concentration = 0.04 µ g   3. m SCREAM model, background concentration = 0.04 µ g   3. n CALINE4 and ISCLT models: > 250 m beside expressway. o CALINE4 model: < 250 m beside expressway.  = no data 5 10 Manganese   February 2003 combined with elevated levels of particulates, manganese concentrations were estimated to be two orders of magnitude higher in the underground microenvironment. While these results differed from previous studies where, regardless of MMT use, taxi driver exposures to airborne manganese were higher than office workers' exposures ( Lynam et al., 1994; Zayed et al., 1994; Riveros Rosas et al., 1997), they are consistent with findings cited in Lynam et al. ( 1999) which indicated that subway system commuters in Toronto, Canada had higher manganese exposures than non subway users.

The Particle Total Exposure Assessment Methodology ( PTEAM) study provided information on levels of airborne manganese in Riverside, CA [ findings summarized in Davis et al. ( 1998)]. This study was conducted over a 7 week period in Fall 1990, and utilized personal and stationary monitors to measure indoor and outdoor concentrations of manganese. Study directors used a stratified sampling plan to select 178 individuals over the age of 10 to represent the general population of the region. Each individual was monitored over two 12 hour periods. Personal exposure measurements of manganese associated with PM 10 ( particulate matter of diameter 10 : m or less) indicated that approximately half of the population in Riverside experienced daily exposure to concentrations exceeding 35 ng/ m3. Approximately 1% of the population experienced personal exposures to manganese concentrations above 220 ng/ m3.

Another study measured concentrations of manganese associated with PM in Toronto, Canada during 1995   1996 ( Pellizzari et al., 1999). Residential indoor, outdoor, and personal air samples were collected over 3 day periods. Table 5 6 lists the mean 3 day PM associated manganese concentrations by sample type. Average concentrations for manganese associated with either PM 10 or PM 2.5 ( PM of diameter 2.5 : m or less) were higher in personal monitor samples than in indoor or outdoor air.

Clayton et al. ( 1999) simulated annual exposures to manganese using 3 day personal exposure measurements reported by Pellizari et al. ( 1999). The mean manganese exposure concentration for non occupationally exposed populations was predicted to be 9.2 ng/ m3. Approximately 0.4% and 7.6% of the exposed population were estimated to have annual exposure concentrations greater than 25 ng/ m3 and 15 ng/ m3, respectively ( Clayton et al., 1999).

Table 5 6. Mean Manganese Exposures from 3 day Indoor, Outdoor and Personal Air Samples.

Sample PM 10 associated Mn ( ng/ m3) a PM 2.5 associated Mn ( ng/ m3)

Personal 35.8 13.1 Indoor Air 8.0 5.5 Outdoor Air 17.5 9.7 Source: Pellizzari et al.( 1999). a Estimated from Figure 4 in Pellizarri et al. ( 1999). 5 11 Manganese   February 2003 Populations with Potential for High Exposure Workers in certain occupations may be exposed to significantly higher manganese concentrations than the general population. Historically, the production of manganese fumes or manganese containing dusts in the ferromanganese, iron and steel, dry cell battery manufacturing, welding, and mining industries may result in workplace concentrations as much as 10,000 fold higher than average ambient levels in air ( ATSDR, 2000). ATSDR ( 2000) has noted that data for current occupational levels of manganese exposure are not available. However, to be in compliance with Occupational Safety and Health Administration ( OSHA) regulations, manganese levels in the workplace should not exceed the OSHA time weighted average Permissible Exposure Limit ( PEL) of 1 mg/ m3.

5.2.2 Intake of Manganese in Air General Population U. S. EPA ( 1990) has calculated an average annual atmospheric manganese background concentration of 40 ng/ m3 for urban areas, based on data for 24 hour average concentrations in 102 cities across the U. S. ( U. S. EPA, 1990). Assuming an intake of 15.2 cubic meters per day ( m3/ day) ( U. S. EPA, 1996d), the average estimated daily intake for a 70 kg adult would be 8.7 ng/ kg day. The corresponding average daily intake for a 10 kg child would be 35 ng/ kg day if an inhalation rate of 8.7 m3/ day ( U. S. EPA, 1996d) is assumed. Alternatively, assuming a range of ambient concentrations from 2 to 220 ng/ m3 for rural and urban populations, and an inhalation rate of 15.2 m3/ day, the estimated daily intake range for a 70 kg adult would be 0.43 to 47.8 ng/ kg day. The daily intake for a 10 kg child would range from 1.74 to 122 ng/ kg day. These calculated adult intakes are in general agreement with intakes calculated by others. Loranger and Zayed ( 1997a) predicted a total manganese dose for adults of 1 to 50 ng/ kg day predicted for two urban sites in Montreal, Canada, using Monte Carlo simulation. Zayed et al. ( 1999a) calculated intakes of 5 to 15 ng/ kg day based on measurements of respirable manganese concentrations at five sites in Montreal.

Populations with Potential for High Exposure Historically, workers in occupational settings such as manganese mining or ferromanganese smelting have experienced the potential for high levels of manganese exposure. Published estimates of current occupational exposure levels were not available in the materials reviewed for this document. However, assuming a maximal legal concentration of 1 mg/ m3 and inhalation of 10 m3 of air over the course of a work day, adults exposed to manganese in some occupational settings may have a daily intake as high as 143,000 ng/ kg day ( ATSDR, 2000). 5 12 Manganese   February 2003 5.3 Soil 5.3.1 Concentration of Manganese in Soil Manganese constitutes approximately 0.1% of the earth's crust, and is a naturally occurring component of nearly all soils ( ATSDR, 2000). Natural levels of manganese range from less than 2 to 7,000 mg/ kg, with a geometric mean concentration of 330 mg/ kg ( Shacklette and Boerngen, 1984). The estimated arithmetic mean concentration is 550 mg/ kg. Accumulation of manganese occurs in the subsoil rather than on the soil surface ( ATSDR, 2000). An estimated 60   90% of soil manganese is associated with the sand fraction ( WHO, 1981, as cited in ATSDR, 2000).

5.3.2 Intake of Manganese in Soil General Population No published reports quantify exposure to manganese associated with soil ingestion. Assuming a concentration range of < 2 to 7,000 mg/ kg soil and average ingestion of 50 mg of soil/ day, the average manganese intake of a 70 kg adult would be 0.0014 to 5 : g/ kg day. The corresponding intake for a 10 kg child consuming 100 mg of soil/ day would be 0.02 to 70 : g/ kgday

Populations with Potential for High Exposure No highly exposed populations were identified with respect to soil intake.

5.4 Other Media No published reports identify other sources of manganese exposure.

5.5 Summary of Exposure to Manganese in Media Other Than Water Table 5 7 summarizes information on exposure to manganese in media other than water. Inspection of data in this table reveals that ingestion of food contributes a major proportion of manganese exposure. This observation is consistent with the findings of Loranger and Zayed ( 1995, 1997b), who estimated that food contributed 95 to 99% of the multimedia dose of manganese in Canadian studies. The contribution of soil as a source of manganese was not evaluated in the 1995 study ( Loranger and Zayed, 1995). However, as evident from Table 5 7, soil ingestion has the potential to contribute substantially to intake in areas with naturally high or anthropogenically enriched concentrations of soil manganese.

EPA has derived an oral reference dose ( RfD) for manganese of 0.14 mg/ kg day and an inhalation reference concentration ( RfC) of 5 × 10 5 mg/ m3 ( see Section 8.1). These values can be converted to daily doses ( assuming a 70 kg adult inhaling 15.2 m3/ day of air) of 10 mg and 7.6 × 10 4 mg manganese, respectively. Thus, the level of safe exposure determined for the 5 13 Manganese   February 2003 inhalation route is five orders of magnitude less than that determined for the oral route, reflecting the much greater toxicity observed for inhaled versus ingested manganese. For exposure to manganese from drinking water, EPA recommends applying an additional modifying factor of three to the above RfD, yielding 0.047 mg/ kg day ( U. S. EPA, 1996a). This recommendation derives from concern raised by the Kondakis study ( 1989) ( see Sections 7.1.3 and 8.1) about the potential for higher absorption of manganese from water, and also from consideration of potentially higher absorption in fasting individuals and neonates, the latter of which may have higher absorption rates and lower excretion rates of manganese than mature individuals ( U. S. EPA, 1996a).

For drinking water, a National Secondary Drinking Water Regulation ( or secondary Maximum Contaminant Levels, s MCL) for manganese also exists ( 0.05 mg/ L) to prevent clothes staining and taste problems. Secondary standards are non enforceable guidelines regulating contaminants that may cause aesthetic effects ( such as color, taste or odor) or cosmetic effects ( such as skin or tooth discoloration) in drinking water. EPA recommends s MCLs to water systems but does not require systems to comply.

Table 5 7. Summary of Human Exposure to Manganese in Media Other than Water ( General Population).

PARAMETER EXPOSURE MEDIUM Food Air Soil Adult Child Adult Child Adult Child Concentration in Medium 0.04   47 mg/ kg 40 ng/ m3 < 2   7,000 mg/ kg Estimated Average Daily Intake (: g/ kgday 28.6   126 0.87   37.2 ( infant) 128 ( child) 0.0087 0.034 0.0014   5.0 0.02   70 6 1 Manganese   February 2003 6.0 TOXICOKINETICS The absorption, distribution, metabolism and excretion of manganese in the body are reviewed, discussed, and summarized in Greger ( 1999), U. S. EPA ( 1984), Kies ( 1987), U. S. EPA ( 1993), and ATSDR ( 2000). Age, chemical species, dose, route of exposure, and dietary conditions all affect manganese absorption and retention ( Lönnerdal et al., 1987). Uptake of dietary manganese appears to be controlled by several dose dependent processes: biliary excretion, intestinal absorption, and intestinal elimination. Manganese absorbed in the divalent form from the gut via the portal blood is complexed with plasma proteins that are efficiently removed by the liver. Absorption of manganese via inhalation, intratracheal instillation, or intravenus infusions bypasses the control processes by the gastrointestinal tract. After absorption to the blood system by these alternate routes, manganese is apparently oxidized, and the trivalent manganese binds to transferrin. Transferrin bound trivalent manganese is not as readily removed by the liver, as are protein complexes with divalent manganese. Thus, manganese delivered by these other routes would be available for uptake into tissues for a longer period of time than the orally administered manganese, leading to quantitative differences in tissue uptake ( Andersen et al., 1999).

6.1 Absorption Human Studies The following sections discuss absorption of manganese following oral exposure only. Recent studies show that significant differences exist in the amounts of manganese that are absorbed across different exposure routes, with inhaled manganese being absorbed more rapidly and to a greater extent than ingested manganese ( Roels et al., 1997; Tjälve at al., 1996).

Past manganese intake and iron, phosphorus, and calcium intake affect manganese absorption in humans. Further, phytate, fiber, and polyphenols ( tannins) in vegetable diet tend to decrease manganese absorption ( Greger, 1999; Greger and Snedeker, 1980). Manganese speciation and the route of exposure also affect its absorption ( Andersen et al., 1999; Tjalve et al., 1996).

Mena et al. ( 1969) investigated gastrointestinal absorption of manganese in 11 healthy, fasted human subjects. The subjects received 100 : Ci of 54MnCl 2 with 0.200 mg stable 55MnCl 2 ( 0.087 mg Mn) as a carrier. After 2 weeks of daily whole body counts, the absorption of 54Mn was calculated to average approximately 3%. Comparable absorption values were found for healthy manganese miners and ex miners with chronic manganese poisoning. However, enterohepatic circulation was not taken into account in this study. These values may therefore underestimate absorption ( U. S. EPA, 1993).

Thomson et al. ( 1971) reported a higher absorption rate of 54MnCl 2 in segments of jejunum and duodenum using a double lumen tube. The mean absorption rate in eight subjects was 27 ± 3%. 6 2 Manganese   February 2003 Schwartz et al. ( 1986) studied the absorption and retention of manganese over a 7 week period in seven healthy male volunteers aged 22   32 years. Volunteers consumed 3,100   4,400 kcal/ day which provided levels of manganese ranging from 12.0 to 17.7 mg Mn/ day. Assuming an adult body weight of 70 kg, this intake corresponds to 0.17 to 0.25 mg/ kg day. During weeks 2 to 4, manganese absorption was  2.0 ± 4.9% of the intake. During weeks 5 to 7, the reported absorption was 7.6 ± 6.3%. Despite the high level of intake, net retention of manganese was not observed in these individuals. Fecal loss accounted for nearly all of the ingested manganese, and in some cases exceeded the intake. A portion of this loss likely represents biliary secretion of previously absorbed manganese.

Sandström et al. ( 1986) administered 450 mL of infant formula containing 0.050 mg Mn/ L to eight healthy subjects, aged 20 to 38 years. The average absorption for seven of the subjects was 8.4 ± 4.7%. The eighth subject was diagnosed with iron deficiency anemia, and absorbed 45.5%. Six additional subjects received 2.5 mg of manganese ( as sulfate) in a multielement preparation. The mean absorption for the second group of subjects was 8.9 ± 3.2%.

Davidsson et al. ( 1989b) studied whole body retention of 54Mn in adult humans after intake of radiolabeled infant formula. These authors observed reproducible retention figures at day 10, after repeated administrations of the labeled formula to six subjects. Absorption ranged from 0.8   16%. This range corresponds to a 20 fold difference between the highest and lowest values. The mean value was 5.9 ± 4.8%. Retention at day 10 ranged from 0.6   9.2%, with a mean value of 2.9 ± 1.8% when measured in 14 healthy individuals. These results suggest substantial variation in absorption between individuals.

In addition, Davidsson et al. ( 1989a) studied manganese absorption from human milk, cow's milk, and infant formulas in human adults using extrinsic labeling of the foods with 54Mn or 52Mn and measurements of whole body retention. The fractional manganese absorption from human milk ( 8.2% ± 2.9%) was significantly different when compared with cow's milk ( 2.4% ± 1.7%) or soy formula ( 0.7% ± 0.2%). The total amount of absorbed manganese, however, was significantly higher from the cow's milk formula as compared with human milk.