ADDENDUM TO THE TOXICOLOGICAL PROFILE FOR TRICHLOROETHYLENE Agency for Toxic Substances and Disease Registry Division of Toxicology and Human Health Sciences Atlanta, GA 30333 January 2013 ii TRICHLOROETHYLENE CONTENTS LIST OF TABLES......................................................................................................................... iv LIST OF FIGURES ........................................................................................................................ v Background Statement ................................................................................................................... vi 2. HEALTH EFFECTS.................................................................................................................. 1 2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ......................... 1 2.2.1 Inhalation Exposure .................................................................................................. 1 2.2.2 Oral Exposure ......................................................................................................... 14 2.3 TOXICOKINETICS....................................................................................................... 22 2.3.1 Absorption............................................................................................................... 22 2.3.2 Distribution ............................................................................................................. 23 2.3.3 Metabolism ............................................................................................................. 24 2.3.4 Elimination and Excretion ...................................................................................... 27 2.3.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models28 2.4 MECHANISMS OF ACTION....................................................................................... 39 2.4.2 Mechanisms of Toxicity ......................................................................................... 39 2.5 RELEVANCE TO PUBLIC HEALTH.......................................................................... 42 2.6 BIOMARKERS OF EXPOSURE AND EFFECT......................................................... 48 2.6.1 Biomarkers Used to Identify or Quantify Exposure to Trichloroethylene ............. 48 2.6.2 Biomarkers Used to Characterize Effects Caused by Trichloroethylene ................ 49 2.7 INTERACTIONS WITH OTHER SUBSTANCES ...................................................... 49 2.8 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ................................... 49 2.9 METHODS FOR REDUCING TOXIC EFFECTS ....................................................... 51 2.9.1 Reducing Peak Absorption Following Exposure.................................................... 51 2.9.3 Interfering with the Mechanism of Action for Toxic Effects ................................. 52 2.10 ADEQUACY OF THE DATABASE ............................................................................ 52 2.10.3 Ongoing Studies...................................................................................................... 52 3. CHEMICAL AND PHYSICAL INFORMATION ................................................................. 53 4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL .............................................. 53 4.1 PRODUCTION .............................................................................................................. 53 4.2 IMPORT/EXPORT ........................................................................................................ 56 4.3 USE ................................................................................................................................ 56 4.4 DISPOSAL..................................................................................................................... 56 5. POTENTIAL FOR HUMAN EXPOSURE............................................................................. 57 5.2 RELEASES TO THE ENVIRONMENT ....................................................................... 57 5.2.1 Air ........................................................................................................................... 57 5.2.2 Water....................................................................................................................... 57 5.2.3 Soil .......................................................................................................................... 57 5.3 ENVIRONMENTAL FATE .......................................................................................... 58 5.3.1 Transport and Partitioning ...................................................................................... 58 5.3.2 Transformation and Degradation ............................................................................ 58 5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ..................... 59 5.4.1 Air ........................................................................................................................... 59 5.4.2 Water....................................................................................................................... 61 iii TRICHLOROETHYLENE 5.4.4 Other Environmental Media ................................................................................... 62 5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ............................ 63 5.7 ADEQUACY OF THE DATA BASE ........................................................................... 64 5.7.2 Ongoing Studies...................................................................................................... 64 6. ANALYTICAL METHODS ................................................................................................... 65 6.1 BIOLOGICAL SAMPLES ............................................................................................ 65 6.2 ENVIRONMENTAL SAMPLES .................................................................................. 65 6.3 ADEQUACY OF THE DATABASE ............................................................................ 65 6.3.2 Ongoing Studies...................................................................................................... 65 7. REGULATIONS AND ADVISORIES ................................................................................... 66 8. REFERENCES ........................................................................................................................ 72 APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS .............................. 1 LSE ATTACHMENT..................................................................................................................... 1 iv TRICHLOROETHYLENE LIST OF TABLES 2-1. Levels of Signficant Exposure to Trichloroethylene—Inhalation ..................................LSE-2 2-2. Levels of Signficant Exposure to Trichloroethylene—Oral .........................................LSE-24 2-3. Ongoing Studies of Health Effects of Trichloroethylene ..................................................... 53 4-1. Facilities that Produce, Process, or Use Trichloroethylene .................................................. 54 5-1. Levels of Trichloroethylene Measured in Table-Ready Foods from Across the United States During a 5-Year Study (1996–2000) .......................................................................... 62 5-2. Geometric Mean and Selected Percentiles of Blood Concentrations (in ng/mL) for the U.S. Population from the National Health and Nutrition Examination Survey .............. 63 7-1. Regulations and Guidelines Applicable to Trichloroethylene .............................................. 68 v TRICHLOROETHYLENE LIST OF FIGURES 2-1. Levels of Signficant Exposure to Trichloroethylene—Inhalation ................................LSE-20 2-2. Levels of Signficant Exposure to Trichloroethylene—Oral .........................................LSE-49 2-3. Overall Structure of PBPK Model for TCE and Metabolites............................................... 33 vi TRICHLOROETHYLENE ADDENDUM for TRICHLOROETHYLENE Supplement to the 1997 Toxicological Profile for Trichloroethylene Background Statement This addendum to the Toxicological Profile for Trichloroethylene supplements the profile that was released in 1997. Toxicological profiles are developed in response to the Superfund Amendments and Reauthorization Act (SARA) of 1986 which amended the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). CERCLA mandates that the Administrator of ATSDR prepare toxicological profiles on substances on the CERCLA Priority List of Hazardous Substances and that the profiles be revised “no less often than once every three years”. CERCLA further states that the Administrator will “establish and maintain inventory of literature, research, and studies on the health effects of toxic substances” [Title 42, Chapter 103, Subchapter I, § 9604 (i)(1)(B)]. The purpose of this addendum is to provide, to the public and federal, state, and local agencies a non-peer reviewed supplement of the scientific data that were published in the open peer- reviewed literature since the release of the profile in 1997. Chapter numbers in this addendum coincide with the Toxicological Profile for Trichloroethylene (1997). This document should be used in conjunction with the profile. It does not replace the profile. TRICHLOROETHYLENE 1 2. HEALTH EFFECTS Health effects information made available to the public