EPA-823-R-01-001

January 2001

Water Quality Criterion 

for the Protection of 

Human Health: 

Methylmercury

Final

Office of Science and Technology

Office of Water

U.S. Environmental Protection Agency Washington, DC 20460
ii Methylmercury Water Quality Criterion 1/3/01

NOTICE

This document has been reviewed in accordance with U.S. Environmental Protection Agency

policy and approved for publication. Mention of trade names or commercial products does not constitute

endorsement or recommendation for use.
Methylmercury Water Quality Criterion 1/3/01 iii

ACKNOWLEDGMENTS

Authors

Denis Borum U.S. EPA Office of Science and Technology, Office of Water

Mary Ko Manibusan, M.P.H. U.S. EPA Office of Science and Technology, Office of Water

Rita Schoeny, Ph.D. U.S. EPA Office of Science and Technology, Office of Water

Erik L. Winchester, M.S. U.S. EPA Office of Science and Technology, Office of Water

Contributors

Helen Jacobs, M.S. U.S. EPA Office of Science and Technology, Office of Water

Kate Mahaffey, Ph.D. U.S. EPA Office of Science Co-ordination and Policy, Office of

Prevention, Pesticides and Toxic Substancest

Debra Rice, Ph.D. U.S. EPA National Center for Environmental Assessment, Office of

Research and Development

Keith Sappington, M.S. U.S. EPA National Center for Environmental Assessment, Office of

Research and Development

EPA Reviewers

Larry Hall, Ph.D. U.S. EPA National Health and Environmental Effects Research

Laboratory, Office of Research and Development

John Nichols, Ph.D. U.S. EPA National Health and Environmental Effects Research

Laboratory, Office of Research and Development

Glen Rice, M.S. U.S. EPA National Center for Environmental Assessment, Office of

Research and Development 

Jeff Swartout, M.S. U.S. EPA National Center for Environmental Assessment, Office of

Research and Development

Portions of this document were developed under contract with Great Lakes Environmental Center

(GLEC), Information Systems Solutions International (ISSI), Inc., and ICF Consulting, Inc.
iv Methylmercury Water Quality Criterion 1/3/01

EXTERNAL PEER REVIEWERS

The following individuals provided technical and scientific reviews of the content and scientific

information in the criterion document as part of a formal peer review process.

Methylmercury Reference Dose

Kim N. Dietrich, Ph.D., University of Cincinnati

Bruce A. Fowler, Ph.D., University of Maryland 

Gary Ginsberg, Ph.D. (workshop chair), Connecticut Department of Public Health

Martha Keating, M.S., Keating Environmental

Chris Newland, Ph.D., Auburn University

Pam Shubat, Ph.D., Minnesota Department of Health

Andrew Smith, S.M., Sc.D., Maine Department of Human Services

Bioaccumulation of Methylmercury

Nicolas S. Bloom, M.S., Frontier Geosciences Inc.

James P. Hurley, Ph.D., University of Wisconsin Water Resources Institute

David P. Krabbenhoft, Ph.D., U.S. Geological Survey

David Maschwitz, Ph.D., Minnesota Pollution Control Agency

Darell G. Slotton, Ph.D., University of California

Edward Swain, Ph.D., Minnesota Pollution Control Agency

Potential areas for conflict of interest were investigated via direct inquiry with the peer reviewers

and review of their current affiliations. No conflicts of interest were identified.
Methylmercury Water Quality Criterion 1/3/01 v

CONTENTS

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix

1.0 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1

1.1 Purpose of this Document . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1

1.2 Primary Data Source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-2

1.3 Chemical and Physical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-2

2.0 Toxicokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1

2.1 Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1

2.1.1 Oral Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1

2.1.2 Absorption via Other Routes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1

2.2 Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-2

2.3 Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3

2.4 Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-4

2.5 Biological Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-6

2.5.1 Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-6

2.5.2 Hair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-7

2.5.3 Methods of Analyzing Mercury Concentrations in Biological Samples . . . . . . . . . . . . . 2-7

2.6 Pharmacokinetic Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8

3.0 Toxicological Basis for Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-1

3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-1

3.2 Neurotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-2

3.2.1 Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-2

3.2.2 Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-36

3.3 Cardiovascular Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-41

3.3.1 Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-41

3.3.2 Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-43

3.4 Immunotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-43

3.4.1 Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-43

3.4.2 Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-44

3.5 Reproductive Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-46

3.5.1 Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-46

3.5.2 Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-46

3.6 Genotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-46

3.6.1 Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-46

3.6.2 Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-47

3.7 Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-48

3.7.1 Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-48

3.7.2 Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-49

4.0 Risk Assessment for Methylmercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-1

4.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-1

4.1.1 Other RfDs Published by EPA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-2

4.1.2 Risk Assessments Done by Other Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-7

4.1.3 SAB review of the Mercury Study Report to Congress . . . . . . . . . . . . . . . . . . . . . . . . . . 4-9

4.1.4 Interagency Consensus Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-10

4.1.5 National Academy of Sciences Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-12
vi Methylmercury Water Quality Criterion 1/3/01

4.1.6 External Peer Review of Draft RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-14

4.1.7 Revised RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-14

4.2 Choice of Critical Study and Endpoint . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-15

4.2.1 Summary of Available Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-15

4.2.2 Choice of Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-32

4.2.3 Choice of Critical Effect (endpoint) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-48

4.3 Choice of Dose-Response Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-62

4.3.1 Benchmark Versus NOAEL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-62

4.3.2 Choice of Exposure Metric . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-63

4.3.3 Choice of BMD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-64

4.3.4 Choice of Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-66

4.3.6 Selection of the Point of Departure for the RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-68

4.4 Dose Conversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-68

4.4.1 PBPK Models Versus One-Compartment Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-69

4.4.2 One-Compartment Model for Methylmercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-69

4.5 Choice of Uncertainty Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-77

4.5.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-77

4.5.2 Toxicodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-78

4.5.3 Exposure Estimation as an Area of Uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-79

4.5.4 Pharmacokinetic Variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-79

4.5.5 Uncertainty in Choice of Critical Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-82

4.5.6 Choice of Uncertainty Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-86

4.6 Calculation of the RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-87

5.0 Exposure Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-1

5.1 Overview of Relative Source Contribution Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-1

5.2 Population of Concern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-1

5.3 Overview of Potential for Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-2

5.4 Estimates of Occurrence and Exposure from Environmental Media . . . . . . . . . . . . . . . . . . 5-3

5.4.1 Exposure Intake Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-4

5.4.2 Intake from Drinking Water/ambient Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-5

5.4.3 Nonfish Dietary Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-12

5.4.4 Fish Consumption Estimates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-18

5.4.5 Respiratory Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-30

5.4.6 Soil/Sediment Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-35

5.4.7 Occupational and Other Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-40

5.5 Exposure Data Adequacy and Estimate Uncertainties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-42

5.5.1 Adequacy of Intake Estimate for Drinking Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-42

5.5.2 Intake from Nonfish Dietary Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-43

5.5.3 Intake from Fish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-44

5.5.4 Intake from Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-46

5.5.5 Intake from Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-46

5.6 Total Exposure Estimates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-47

5.7 Relative Source Contribution (RSC) Estimates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-56

5.7.1 RSC Policy Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-56

5.7.2 Target Population for RSC/rationale for Approach to Methylmercury . . . . . . . . . . . . . 5-56

5.7.3 Data Adequacy for RSC Estimate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-57

5.7.4 RSC Estimate/apportionment of the RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-57
Methylmercury Water Quality Criterion 1/3/01 vii

6.0 Mercury Bioaccumulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-1

6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-1

6.2 Issues in Developing Methylmercury BAFs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-1

6.3 Consideration of Fish Tissue Residue Criterion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-4

7.0 Water Quality Criterion Calculation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-1

7.1 Equation for Tissue Residue Concentration and Parameters Used . . . . . . . . . . . . . . . . . . . . . 7-1

7.2 Site-Specific or Regional Adjustments to Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-1

8.0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . R-1

Appendix A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A-1

Section I: Draft National Methylmercury Bioaccumulation Factors . . . . . . . . . . . . . . . . . . . . . . A-1

Section II: Chemical Translators for Mercury and Methylmercury . . . . . . . . . . . . . . . . . . . . . A-19
viii Methylmercury Water Quality Criterion 1/3/01
Methylmercury Water Quality Criterion 1/3/01 ix

EXECUTIVE SUMMARY

About This Document

This document is the basis for a human health Ambient Water Quality Criterion (AWQC) for

methylmercury. This AWQC replaces the AWQC for total mercury in published in 1980 and partially

updated in 1997. Under Section 304(a) of the Clean Water Act, EPA must periodically revise criteria for

water quality to accurately reflect the latest scientific knowledge on the kind and extent of all identifiable

effects of pollutants on human health. 

This document uses new methods and information described in the Methodology for Deriving

Ambient Water Quality Criteria for the Protection of Human Health (2000) (2000 Human Health

Methodology) (U.S. EPA, 2000a,b). These new methods include updated approaches to determine

toxicity dose-response relationships for both carcinogenic and noncarcinogenic effects, updated

information for determining exposure factors, and new procedures to determine bioaccumulation factors. 

The Mercury Study Report to Congress (MSRC) (U.S. EPA, 1997), an eight-volume report

prepared by the U.S. Environmental Protection Agency (EPA) and submitted to Congress in 1997, serves

as a primary information source on methylmercury. However, as the state of the science for

methylmercury is continuously and rapidly evolving, the information from the MSRC has been

supplemented by inclusion of published information since 1997. 

Exposure to Methylmercury

The major pathway for human exposure to methylmercury is consumption of contaminated fish. 

Dietary methylmercury is almost completely absorbed into the blood and is distributed to all tissues

including the brain; it also readily passes through the placenta to the fetus and fetal brain.

Major Health Effects of Methylmercury

Methylmercury is a highly toxic substance with a number of adverse health effects associated with

its exposure in humans and animals. Epidemics of mercury poisoning following high-dose exposures to

methylmercury in Japan and Iraq demonstrated that neurotoxicity is the health effect of greatest concern.

These epidemics led to observation of methylmercury effects on the fetal nervous system. High-dose
x Methylmercury Water Quality Criterion 1/3/01

human exposure results in mental retardation, cerebral palsy, deafness, blindness, and dysarthria in utero

and in sensory and motor impairment in adults. Although developmental neurotoxicity is currently

considered the most sensitive health endpoint, data on cardiovascular and immunological effects are

beginning to be reported and provide more evidence for toxicity from low-dose methylmercury exposure. 

Three large prospective epidemiology studies in the Seychelles Islands, New Zealand, and the

Faroe Islands were designed to evaluate childhood development and neurotoxicity in relation to fetal

exposures to methylmercury in fish-consuming populations. Prenatal methylmercury exposures in these

three populations were within the range of some U.S. population exposures. No adverse effects were

reported from the Seychelles Islands study, but children in the Faroe Islands exhibited subtle

developmental dose-related deficits at 7 years of age. These effects include abnormalities in memory,

attention, and language. In the New Zealand prospective study, children at 4 and 6 years of age exhibited

deficiencies in a number of neuropsychological tests.

In addition to the three large epidemiological studies, studies on both adults and children were

conducted in the Amazon; Ecuador; French Guiana; Madeira; Mancora, Peru; northern Quebec; and

Germany. Effects of methylmercury on the nervous system were reported in all but the Peruvian

population. 

Other Health Effects of Methylmercury

Methylmercury causes chromosomal effects but does not induce point mutations. The MSRC

concluded that because there are data for mammalian germ-cell chromosome aberration and limited data

from a heritable mutation study, methylmercury is placed in a group of high concern for potential human

germ-cell mutagenicity. There is no two-generation study of reproductive effects, but shorter term

studies in rodents, guinea pigs and monkeys have reported observations consistent with reproductive

deficits. There are no data to indicate that methylmercury is carcinogenic in humans, and it induces

tumors in animals only at highly toxic doses. Application of the proposed revisions to the Guidelines for

Cancer Risk Assessment (EPA 1999)leads to a judgment that methylmercury is not likely to be

carcinogenic for humans under conditions of exposure generally encountered in the environment. 
Methylmercury Water Quality Criterion 1/3/01 xi

Quantitative Risk Estimate for Methylmercury

The quantitative health risk assessment for a noncarcinogen relies on a reference dose (RfD). This

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 health effects during a lifetime. To derive an RfD, one first establishes a no adverse effect

level (NOAEL) for a particular endpoint. This can be done by inspection of the available data or by

using a mathematical modeling procedure to estimate the NOAEL; the latter approach was used for

methylmercury. Next the NOAEL is divided by a numerical uncertainty factor to account for areas of

variability and uncertainty in the risk estimate. 

There has been considerable discussion within the scientific community regarding the level of

exposure to methylmercury that is likely to be without an appreciable risk of deleterious health effects

during a lifetime. In 1999, the Congress directed EPA to contract with the National Research Council

(NRC) of the National Academy of Sciences to evaluate the body of data on the health effects of

methylmercury. NRC was to concentrate on new data since the 1997 MSRC, and to provide

recommendations regarding issues relevant to the derivation of an appropriate RfD for methylmercury.

NRC published their report, Toxicological Effects of Methylmercury, in 2000. EPA generally concurred

with the NRC findings and recommendations. The NRC document was used as a resource in determining

the EPA RfD for methylmercury documented here.

Choice of Study

The adverse effect of methylmercury observed at lowest dose is neurotoxicity, particularly in

developing organisms. The brain is considered the most sensitive target organ for which there are data

suitable for derivation of an RfD. There is an extensive array of peer-reviewed, well-analyzed data from

human studies of low-dose exposure to methylmercury. NRC and EPA considered three epidemiologic

longitudinal developmental studies suitable for quantitative risk assessment: the Seychelles Child

Development Study (SCDS); the ongoing studies of children in the Faroe Islands; and the study of

children in New Zealand. All cohorts consisted of children exposed in utero through maternal

consumption of mercury-contaminated fish or marine mammals. In all studies there were

biomarkers of maternal exposure (hair), and in the Faroes study cord blood was also used as an additional

measure of fetal exposure. The SCDS yielded no evidence of impairment related to methylmercury

exposure, but the two other studies have found dose-related adverse effects on a number of
xii Methylmercury Water Quality Criterion 1/3/01

neuropsychological endpoints. EPA chose to base the RfD on data from the Faroes study. The SCDS has

no findings of effects associated with methylmercury exposure, and thus is not the best choice for a

public health protective risk estimate. While the New Zealand study does show mercury-related effects it

relatively small by comparison to the other two. Advantages of the Faroes study include these: 

• Large sample size (n > 900 for some measures)

• Good statistical power as calculated by conventional means

• Use of two different biomarkers of exposure

• Comprehensive and focused neuropsychological assessment 

• Assessment at an age and state of development when effects on complex neuropsychological

functions are most likely to be detectable

• Statistically significant observations which remain after adjusting for potential PCB effects 

• Extensive scrutiny in the epidemiological literature

The Faroe Islands study was used for derivation of the RfD.

Estimation of the No Adverse Effect Level

A benchmark dose analysis was chosen as the most appropriate method of quantifying the doseeffect relationship. The level chosen was a Benchmark Dose Lower Limit (BMDL); this was the lower

95% limit on a 5% effect level obtained by applying a K power model (K  1) to dose-response data

based on mercury in cord blood. The BMDL was chosen as the functional equivalent of a no-adverseeffect level for calculation of the RfD. 

Choice of Endpoint

Several endpoints are sensitive measures of methylmercury effects in the Faroese children. EPA

considered the recommendations of the NRC and EPA’s external scientific peer review panel in coming

to a decision as to the appropriate endpoint. The NRC recommended the use of a BMDL of 58 ppb

mercury in cord blood from the Boston Naming Test (BNT). The external peer panel felt that the BNT

scores showed an effect of concomitant PCB exposure in some analyses. They preferred a PCB-adjusted

BMDL of 71 ppb mercury in cord blood for the BNT. A difficulty with this choice is that this BMDL is

based on scores from only about one-half of the total cohort. The peer panel further suggested using a

composite index across several measures in the Faroes data set. EPA prepared a comparison of the
Methylmercury Water Quality Criterion 1/3/01 xiii

endpoints recommended by NRC and peer reviewers; this also included the BMDLs from the NRC

integrative analysis and geometric means of four scores from the Faroes. These BMDLs and

corresponding estimates of ingested methylmercury are within a very small range. Rather than choosing

a single measure for the RfD critical endpoint, EPA considers that this RfD is based on several scores.

These test scores are all indications of neuropsychological processes related to the ability of a child to

learn and process information. 

Calculation of Ingested Methylmercury Dose

In the risk assessment discussion EPA uses the NRC-recommended BMDL of 58 ppb mercury in

cord blood as an example in the dose conversion and RfD calculation. The BMDL in terms of mercury

in cord blood was converted to an estimate of ingested methylmercury. This was done by use of a onecompartment model similar to that used in the MSRC. Single-parameter estimates were used rather than

a distributional approach. It was assumed that the cord blood methylmercury level was equal to

maternal blood level. The ingested dose of methylmercury that corresponds to a cord blood level of 58

ppb is 1.081 g/kg bw/day. 

Uncertainty Factor

 Several sources of variability and uncertainty were considered in the application of a composite

uncertainty factor of 10. This included a factor of 3 for pharmacokinetic variability and uncertainty; one

area of pharmacokinetic uncertainty was introduced with the assumption of equivalent cord blood and

maternal blood mercury levels. An additional factor of 3 addressed pharmacokinetic variability and

uncertainty. Other areas of concern include inability to quantify possible long-term sequelae for

neurotoxic effects, questions as to the possibility of observing adverse impacts (such as cardiovascular

effects) below the BMDL, and lack of a two-generation reproductive effects assay.

Methylmercury Reference Dose

 The RfD derived in this assessment is 0.1 g/kg bw/day or 1x10-4 mg/kg bw/day. The RfD for

methylmercury was not calculated to be a developmental RfD only. It is intended to serve as a level of

exposure without expectation of adverse effects when that exposure is encountered on a daily basis for a

lifetime. In the studies so far published on subtle neuropsychological effects in children, there has been

no definitive separation of prenatal and postnatal exposure that would permit dose-response modeling. 
xiv Methylmercury Water Quality Criterion 1/3/01

That is, there are currently no data that would support the derivation of a child (vs. general population)

RfD. 

Relative Source Contribution

The assessment of methylmercury exposure from common media sources (e.g., diet, air) and

relative source contribution (RSC) estimates follows the 2000 Human Health Methodology. The RSC is

used to adjust the RfD to ensure that the water quality criterion is protective, given other anticipated

sources of exposure. The exposure assessment characterizes the sources of methylmercury exposure in

environmental media, providing estimates of intake from the relevant sources for children, women of

childbearing age, and adults in the general population. Based on available data, human exposures to

methylmercury from all media sources except freshwater/estuarine and marine fish are negligible, both in

comparison with exposures from fish and compared with the RfD. Estimated exposure from ambient

water, drinking water, nonfish dietary foods, air, and soil are all, on average, at least several orders of

magnitude less than those from freshwater/estuarine fish intakes. Therefore, these exposures were not

factored into the RSC. However, ingestion of marine fish is a significant contributor to total

methylmercury exposure. For the methylmercury criterion, the RSC is the estimated exposure from

marine fish intake. This is subtracted from the RfD when calculating the water quality criterion. One

hundred percent of the mercury in marine fish was assumed to be present as methylmercury. The

estimated average exposure to methylmercury from marine fish is 2.7 x 10-5 mg/kg-day. This exposure

represents almost 30% of the RfD.

Methylmercury Bioaccumulation

Methylmercury is a chemical that bioaccumulates and biomagnifies in aquatic food webs. The

fates of mercury and methylmercury in the environment are complex processes affected by numerous

biotic and abiotic factors that are subjects of ongoing research. Methylation of mercury is a key step in

the entrance of mercury into food chains. The biotransformation of inorganic mercury forms to

methylated organic forms in water bodies can occur in the sediment and the water column. Inorganic

mercury can be absorbed by aquatic organisms but is generally taken up at a slower rate and with lower

efficiency than is methylmercury. Methylmercury continues to accumulate in fish as they age. Predatory

organisms at the top of aquatic and terrestrial food webs generally have higher methylmercury

concentrations because methylmercury is typically not completely eliminated by organisms and is 
Methylmercury Water Quality Criterion 1/3/01 xv

transferred up the food chain. Nearly 100% of the mercury that bioaccumulates in upper-trophic-level

fish (predator) tissue is methylmercury.

Numerous factors can influence the bioaccumulation of mercury in aquatic biota. These include,

but are not limited to, the acidity (pH) of the water, length of the aquatic food chain, temperature, and

dissolved organic material. Physical and chemical characteristics of a watershed, such as soil type and

erosion or proportion of area that is wetlands, can affect the amount of mercury that is transported from

soils to water bodies. Interrelationships among these factors are poorly understood and are likely to be

site-specific. No single factor (including pH) has been correlated with extent of mercury

bioaccumulation in all cases examined. Two lakes that are similar biologically, physically, and

chemically can have different methylmercury concentrations in water, fish, and other aquatic organisms.

The Methylmercury Criterion is a Fish Tissue Residue Criterion

EPA concluded that it is more appropriate at this time to derive a fish tissue (including shellfish)

residue water quality criterion for methylmercury rather than a water column-based water quality

criterion. This decision considered issues of mercury fate in the environment, the NRC report on the

toxicological effects of mercury, and in particular the methylmercury peer review comments. EPA

believes a fish tissue residue water quality criterion is appropriate for many reasons. Such a criterion

integrates spatial and temporal complexity that occurs in aquatic systems and that affects methylmercury

bioaccumulation. A fish tissue residue water quality criterion is more closely tied to the CWA goal of

protecting the public health because it is based directly on the dominant human exposure route for

methylmercury. The concentration of methylmercury is also generally easier to quantify in fish tissue

than in water and is less variable over the time periods in which water quality standards are typically

implemented in water quality-based. Thus, the data used in permitting activities can be based on a more

consistent and measurable endpoint. A fish tissue residue criterion is also consistent with how fish

advisories are issued. Fish advisories for mercury are based on the amount of methylmercury in fish

tissue that is considered acceptable, although they are usually issued for a certain fish or shellfish species

in terms of a meal size. A fish tissue residue water quality criterion should enhance harmonization

between these two approaches for protecting the public health. 

The methylmercury water quality criterion is, thus, a concentration in fish tissue. It was calculated

using the criterion equation in the 2000 Human Health Methodology rearranged to solve for a protective

concentration in fish tissue rather than in water. 
xvi Methylmercury Water Quality Criterion 1/3/01

TRC = BW RfD RSC - 

F Ii i

×

∑ =

( )

2

4

Where:

TRC = Fish tissue residue criterion (mg methylmercury/kg fish) for freshwater and estuarine fish

RfD = Reference dose (based on noncancer human health effects) of 0.0001 mg

methylmercury/kg body weight-day

RSC = Relative source contribution (subtracted from the RfD to account for marine fish

consumption) estimated to be 2.7 x 10-5 mg methylmercury/kg body weight-day

BW = Human body weight default value of 70 kg (for adults)

FI = Fish intake at trophic level (TL) i (i = 2, 3, 4); total default intake is 0.0175 kg fish/day

for general adult population. Trophic level breakouts for the general population are: TL2

= 0.0038 kg fish/day; TL3 = 0.0080 kg fish/day; and TL4 = 0.0057 kg fish/day. 

The resulting Tissue Residue Criterion is 0.3 mg methylmercury/kg fish. This is the concentration in fish

tissue that should not be exceeded based on a total fish and shellfish consumption-weighted rate of

0.0175 kg fish/day. EPA strongly encourages States and authorized Tribes to develop a water quality

criterion for methylmercury using local or regional data rather than the default values if they believe that

such a water quality criterion would be more appropriate for their target population.