ADDENDUM TO THE TOXICOLOGICAL PROFILE FOR FORMALDEHYDE Agency for Toxic Substances and Disease Registry Division of Toxicology and Environmental Medicine Atlanta, GA 30333 October 2010 FORMALDEHYDE ii CONTENTS LIST OF FIGURES ..................................................................................................................................... iv LIST OF TABLES........................................................................................................................................ v Background Statement ................................................................................................................................. vi 2. HEALTH EFFECTS................................................................................................................................ 1 2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE .....................................................1 2.2.2 Oral Exposure .................................................................................................................................... 58 2.2.3 Dermal Exposure ............................................................................................................................... 64 2.3 TOXICOKINETICS .................................................................................................................................. 66 2.3.3 Metabolism ........................................................................................................................................ 66 2.3.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ..........................66 2.4 MECHANISMS OF ACTION ................................................................................................................... 70 2.4.1 Pharmacokinetic Mechanisms ........................................................................................................... 70 2.4.3 Animal-to-Human Extrapolations ..................................................................................................... 73 2.5 Relevance to Public Health ........................................................................................................................ 74 2.6 CHILDREN’S SUSCEPTIBILITY ............................................................................................................ 75 2.7 BIOMARKERS OF EXPOSURE AND EFFECT .....................................................................................76 2.7.1 Biomarkers Used to Identify or Quantify Exposures to Formaldehyde .............................................76 2.7.2 Biomarkers Used to Characterize Effects Caused by Formaldehyde ................................................78 2.8 INTERACTIONS WITH OTHER CHEMICALS .....................................................................................79 2.10 METHODS FOR REDUCING TOXIC EFFECTS ...................................................................................79 2.10.1 Reducing Peak Absorption Following Exposure ...............................................................................80 2.10.2 Reducing Body Burden ..................................................................................................................... 81 2.11 ADEQUACY OF THE DATABASE ........................................................................................................ 81 2.11.2 Identification of Data Needs .............................................................................................................. 81 2.11.3 Ongoing Studies ................................................................................................................................ 82 3. CHEMICAL AND PHYSICAL INFORMATION ................................................................................ 83 4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL ............................................................ 83 4.1 PRODUCTION .......................................................................................................................................... 83 4.2 IMPORT/EXPORT .................................................................................................................................... 90 4.3 USE ............................................................................................................................................................ 90 4.4 DISPOSAL ................................................................................................................................................. 93 5. POTENTIAL FOR HUMAN EXPOSURE ........................................................................................... 94 5.1 OVERVIEW .............................................................................................................................................. 94 5.2 RELEASES TO THE ENVIRONMENT ................................................................................................... 94 5.2.1 Air ..................................................................................................................................................... 95 5.2.2 Water ............................................................................................................................................... 101 5.2.3 Soil .................................................................................................................................................. 101 5.3 ENVIRONMENTAL FATE .................................................................................................................... 102 5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ................................................103 5.4.1 Air ................................................................................................................................................... 103 5.4.2 Water ............................................................................................................................................... 105 5.4.4 Other Environmental Media ............................................................................................................ 105 5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ......................................................106 5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ............................................................107 5.8.2 Ongoing Studies .............................................................................................................................. 108 6. ANALYTICAL METHODS ............................................................................................................... 111 6.1 BIOLOGICAL MATERIALS .................................................................................................................. 111 6.2 ENVIRONMENTAL SAMPLES ............................................................................................................ 111 FORMALDEHYDE iii 6.3 ADEQUACY OF THE DATABASE ...................................................................................................... 114 6.3.2 Ongoing Studies .............................................................................................................................. 114 7. REGULATIONS, ADVISORIES, AND GUIDELINES ..................................................................... 115 8. REFERENCES .................................................................................................................................... 122 FORMALDEHYDE iv LIST OF FIGURES 2-1. Health Effects of Breathing Formaldehyde ............................................................................ 2 2-2. Health Effects of Ingesting Formaldehyde ............................................................................. 3 FORMALDEHYDE v LIST OF TABLES 2-1. Genotoxicity of Formaldehyde In Vivo ................................................................................ 40 2-2. Genotoxicity of Formaldehyde In Vitro ............................................................................... 44 2-3. Human Case Reports—Ingestion of Formalin ..................................................................... 59 4-1. U.S. Formaldehyde Capacity and Production ...................................................................... 85 4-2. Facilities that Produce, Process, or Use Formaldehyde ........................................................ 87 4-3. Distribution of Formaldehyde Production According to Uses in the United States ............. 92 5-1. Releases to the Environment from Facilities that Produce, Process, or Use Formaldehyde ...................................................................................................................... 96 5-2. The Contribution of Various Atmospheric Environments to the Average Exposure to Formaldehyde .................................................................................................................... 107 5-3. Ongoing Studies on Formaldehyde .................................................................................... 109 6-1. Analytical Methods for Determining Formaldehyde in Biological Materials .................... 111 6-2. Analytical Methods for Determining Formaldehyde in Environmental Samples .............. 112 6-3. Ongoing Studies on Formaldehyde .................................................................................... 114 7-1. Regulations, Advisories, and Guidelines Applicable to Formaldehyde ............................. 117