United States Office of Science and EPA-822-R-05-011 Environmental Technology November 15, 2005 Protection Agency Washington, D.C. EPA Office of Water DRINKING WATER CRITERIA DOCUMENT FOR BROMINATED TRIHALOMETHANES Prepared for Health and Ecological Criteria Division Office of Science and Technology Office of Water U.S. Environmental Protection Agency Washington, D.C. 20460 under EPA Contract No. 68-C-02-206 Work assignment 3-16 by Syracuse Research Corporation 6225 Running Ridge Road North Syracuse, NY 13212 Under subcontract to The Cadmus Group, Inc. 135 Beaver Street Waltham, MA 02452 FOREWORD Section 1412 (b) (3) (A) of the Safe Drinking Water Act, as amended in 1986, requires the Administrator of the Environmental Protection Agency to publish Maximum Contaminant Level Goals (MCLGs) and promulgate National Primary Drinking Water Regulations for each contaminant, which, in the judgment of the Administrator, may have an adverse effect on public health and which is known or anticipated to occur in public water systems. The MCLG is nonenforceable and is set at a level at which no known or anticipated adverse health effects in humans occur and which allows for an adequate margin of safety. Factors considered in setting the MCLG include health effects data and sources of exposure other than drinking water. This document provides the health effects basis to be considered in establishing the MCLGs for brominated trihalomethanes found in chlorinated drinking water. To achieve this objective, data on pharmacokinetics, human exposure, acute and chronic toxicity to animals and humans, epidemiology and mechanisms of toxicity were evaluated. Specific emphasis is placed on literature data providing dose-response information. Thus, while the literature search and evaluation performed in support of this document was comprehensive, only the reports considered most pertinent in the derivation of the MCLGs are cited in this document. The comprehensive literature search in support of this document includes information published up to January, 2005; however, more recent information may have been added during the review process. When adequate health effects data exist, Health Advisory values for less than lifetime exposure (One-day, Ten-day and Longer-term, approximately 10% of an individual's lifetime) are included in this document. These values are not used in setting the MCLGs, but serve as informal guidance to municipalities and other organizations when emergency spills or contamination situations occur. Ephraim King Director, Office of Science and Technology Office of Water Acknowledgments This document is derived and updated/expanded of the Draft for the Drinking Water Criteria Document on Trihalomethanes (U.S. EPA, 1994), Summary of New Health Effects Data on Drinking Water Disinfectants and Disinfection Byproducts (D/DBPs) for the Notice of Availability (NODA) (U.S.EPA, 1997), and Draft Drinking Water Criteria Document on Brominated Trihalomethanes (U.S. EPA, 2003). This document includes and evaluation of literature on brominated trihalomethanes resulting from full literature searches conducted up to January 2005 for toxicity data. In addition, few newer studies identified after the literature search date have been included as available at the time of document preparation. Contracting Officer Renita Tyus Cincinnati, OH, USEPA Project Officer Jane Holtorf Office of Water, USEPA Work Assignment Manager Nancy Chiu Office of Science and Technology, USEPA Authors Lori Moilinen, Ph.D., DABT Syracuse Research Corporation Nancy Chiu, Ph.D. Office of Science and Technology, USEPA Julie Stickney, Ph.D., DABT Syracuse Research Corporation Other Contractor Technical Support Frank Letkiewicz, B.S. The Cadmus Group, Inc. Karen Ferrante, M.S. The Cadmus Group Inc. Madhulika Nataraja, M.S.E The Cadmus Group Inc. Reviewers This document has been peer reviewed by both EPA scientists and by scientists external to EPA. Internal EPA Reviewers Bob Beliles, Ph.D. National Center for Environmental Assessment, Office of Research & Development, USEPA Jennifer Jinot, Ph.D. National Center for Environmental Assessment, Office of Research & Development, USEPA Bob Sonawane, Ph.D. National Center for Environmental Assessment, Office of Research & Development, USEPA External Peer Reviewers Hudy Buelke-Sam, M.A. Toxicology Services, Greenfield, Indiana Annette Loch Bunge, Ph.D. Professor, Department of Chemical Engineering, Colorado School of Mines, Golden, Colorado John Reif, M.Sc., D.V.M. Department Head, Department of Environmental Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado TABLE OF CONTENTS External Peer Reviewers ........................................................4 I. EXECUTIVE SUMMARY ............................................. I - 1 II. PHYSICAL AND CHEMICAL PROPERTIES ............................ II - 1 A. Properties .................................................... II - 1 B. Summary .................................................... II - 2 III. TOXICOKINETICS ................................................. III - 1 A. Absorption ................................................... III - 1 B. Distribution .................................................. III - 3 C. Metabolism .................................................. III - 5 D. Excretion ................................................... III - 15 E. Bioaccumulation and Retention .................................. III - 15 F. Summary ................................................... III - 15 IV. HUMAN EXPOSURE................................................ IV - 1 A. Occurrence in Drinking Water .................................... IV - 1 1. National Surveys ........................................ IV - 2 2. Other Studies ........................................... IV - 8 3. Estimates of Tap Water Ingestion Exposure to Brominated Trihalomethanes........................................ IV - 13 B. Exposure from Sources Other Than Drinking Water ................. IV - 17 1. Dietary Intake ......................................... IV - 17 2. Air Intake ............................................. IV - 20 3. Concentrations and Exposures Associated with Swimming Pools and Hot Tubs ................................................. IV - 27 4. Soil Concentrations and Exposure .......................... IV - 30 C. Overall Exposure ............................................. IV - 30 D. Body Burden ................................................ IV - 31 1. Blood ................................................ IV - 31 2. Mother's Milk.......................................... IV - 35 E. Summary ................................................... IV - 35 V. HEALTH EFFECTS IN ANIMALS ..................................... V - 1 A. Acute Exposures .............................................. V - 1 1. Bromodichloromethane ................................... V - 1 2. Dibromochloromethane ................................... V - 6 3. Bromoform............................................. V - 7 B. Short-Term Exposures .......................................... V - 8 1. Bromodichloromethane .................................. V - 14 2. Dibromochloromethane .................................. V - 22 i 3. Bromoform............................................ V - 25 C. Subchronic Exposure .......................................... V - 28 1. Bromodichloromethane .................................. V - 31 2. Dibromochloromethane .................................. V - 33 3. Bromoform............................................ V - 34 D. Chronic Exposure ............................................ V - 35 1. Bromodichloromethane .................................. V - 37 2. Dibromochloromethane .................................. V - 41 3. Bromoform............................................ V - 42 E. Reproductive and Developmental Effects .......................... V - 43 1. Bromodichloromethane .................................. V - 43 2. Dibromochloromethane .................................. V - 59 3. Bromoform............................................ V - 62 F. Mutagenicity and Genotoxicity .................................. V - 70 1. Bromodichloromethane .................................. V - 70 2. Dibromochloromethane .................................. V - 78 3. Bromoform............................................ V - 84 G. Carcinogenicity .............................................. V - 90 1. Bromodichloromethane .................................. V - 90 2. Dibromochloromethane ................................. V - 101 3. Bromoform........................................... V - 104 H. Other Key Health Effects ...................................... V - 108 1. Immunotoxicity ....................................... V - 108 2. Hormonal Disruption ................................... V - 110 3. Structure-Activity Relationships .......................... V - 117 I. Summary .................................................. V - 118 1. Health Effects of Acute and Short Term Exposure of Animals . V - 118 2. Health Effects of Longer-term Exposure of Animals .......... V - 118 3. Reproductive and Developmental Effects ................... V - 119 4. Mutagenicity and Genotoxicity ........................... V - 120 5. Carcinogenicity and Related Studies in Animals ............. V - 120 6. Other Key effects ...................................... V - 121 VI. HEALTH EFFECTS IN HUMANS ............................... VI - 1 A. Clinical Case