Development Support Document Final September 14, 2015 Propionaldehyde CAS Registry Number: 123-38-6 Prepared by Stephanie Shirley, Ph.D. Toxicology Division Office of the Executive Director TEXAS COMMISSION ON ENVIRONMENTAL QUALITY Propionaldehyde Page i TABLE OF CONTENTS TABLE OF CONTENTS ............................................................................................................................. I LIST OF TABLES ......................................................................................................................................................II LIST OF FIGURES ....................................................................................................................................................II CHAPTER 1 SUMMARY TABLES .......................................................................................................................... 1 CHAPTER 2 MAJOR SOURCES AND USES ......................................................................................................... 5 CHAPTER 3 ACUTE EVALUATION ...................................................................................................................... 5 3.1 HEALTH-BASED ACUTE REV AND ESL ................................................................................................ 5 3.1.1 Physical/Chemical Properties ..................................................................................................................... 6 3.1.2 Key Human Study (Sim and Pattle 1957) .................................................................................................... 6 3.1.3 Supporting Animal Studies ........................................................................................................................ 6 3.1.3.1 Acute Lethality ...................................................................................................................................................... 6 3.1.3.2 Acute Non-lethal Toxicity ..................................................................................................................................... 7 3.1.4 Mode-of-Action (MOA) Analysis and Dose Metric ................................................................................... 12 3.1.4.1 Metabolism and Pharmacokinetics .................................................................................................................. 12 3.1.4.2 Toxicodynamics and Toxicokinetics ................................................................................................................... 12 3.1.5 Point of Departure (POD) for Key Study ................................................................................................. 13 3.1.6 Dosimetric Adjustments and Adjustments of the PODHEC ........................................................................ 13 3.1.6.1 Exposure Duration Adjustments ......................................................................................................................... 13 3.1.6.2 Adjustments of the PODHEC ................................................................................................................................ 13 acute 3.1.7 Acute ReV and ESL............................................................................................................................ 14 3.1.8 Comparison of TCEQ’s Acute ReV to Other Available Values ................................................................ 15 3.2 WELFARE-BASED ACUTE ESLS .......................................................................................................... 15 3.2.1 Odor Perception ........................................................................................................................................ 15 3.2.2 Vegetation Effects .................................................................................................................................... 15 3.3 SHORT-TERM ESL AND VALUES FOR AIR MONITORING EVALUATION .......................................... 15 3.4 ACUTE INHALATION OBSERVED ADVERSE EFFECT LEVEL ............................................................. 16 CHAPTER 4 CHRONIC EVALUATION............................................................................................................... 16 4.1 NONCARCINOGENIC POTENTIAL ........................................................................................................ 16 4.1.1 Physical/Chemical Properties .................................................................................................................. 16 4.1.2 Key and Supporting Studies ..................................................................................................................... 17 4.1.2.1 Human Studies .................................................................................................................................................... 17 4.1.2.2 Key Animal Study (Union Carbide 1993) ........................................................................................................... 17 4.1.2.3 Supporting Animal Studies ................................................................................................................................. 18 4.1.2.4 Reproductive/Developmental Toxicity ............................................................................................................... 18 4.1.3 Mode of Action and Dose Metric ............................................................................................................. 19 4.1.4 PODs for Key Study and Critical Effect .................................................................................................. 19 4.1.5 Dosimetric Adjustments ............................................................................................................................ 20 4.1.5.1 Exposure Duration Adjustments ......................................................................................................................... 20 4.1.5.2 POD Human Equivalent Concentration (PODHEC) .............................................................................................. 20 4.1.6 Adjustments of the PODHEC ....................................................................................................................... 21 4.1.7 Health-Based Chronic ReV and chronicESLthreshold(nc) ........................................................................... 21 4.1.8 Comparison of TCEQ’s Chronic ReV to USEPA’s Chronic Reference Concentration ............................ 22 4.2 CARCINOGENIC POTENTIAL ........................................................................................................... 23 4.2.1 Summary.................................................................................................................................................... 23 4.2.2 Genotoxicity/mutagenicity ......................................................................................................................... 24 4.2.2.1 In vitro studies ..................................................................................................................................................... 24 Propionaldehyde Page ii 4.2.2.2 In vivo studies ..................................................................................................................................................... 24 4.3 WELFARE-BASED CHRONIC ESL ....................................................................................................... 25 4.4 LONG-TERM ESL AND VALUES FOR AIR MONITORING EVALUATION ............................................ 25 4.5 CHRONIC INHALATION OBSERVED ADVERSE EFFECT LEVEL ......................................................... 25 CHAPTER 5 REFERENCES ................................................................................................................................... 26 APPENDIX A BENCHMARK DOSE MODELING .............................................................................................. 31 APPENDIX B UNCERTAINTY ANALYSIS ......................................................................................................... 36 APPENDIX C OTHER STUDIES AND DOCUMENTS REVIEWED BY THE TD.......................................... 38 LIST OF TABLES Table 1. Air Monitoring Comparison Values (AMCVs) for Ambient Air ................................................... 1 Table 2. Air Permitting Effects Screening Levels (ESLs) ............................................................................ 2 Table 3. Chemical and Physical Data ........................................................................................................... 4 Table 4. Summary of Acute Animal Inhalation Studies ............................................................................... 9 Table 5. Derivation of the Acute ReV and acuteESL .................................................................................... 14 Table 6 Derivation of the Chronic ReV and acuteESL .................................................................................. 22 LIST OF FIGURES Figure 1. Comparison of Regulatory Levels for Propionaldehyde ............................................................... 3 Figure 2. Exposure Response Array for Propionaldehyde .......................................................................... 11 Propionaldehyde Page iii Acronyms and Abbreviations Acronyms and Definitions Abbreviations A animals AEGL Acute Exposure Guideline Level AIC Akaike’s Information Criterion AMCV Air