Development Support Document Final, July 8, 2016 Diisopropylamine CAS Registry Number: 108-18-9 Prepared by Roberta L. Grant, Ph.D. Jong-Song Lee, Ph.D. Pallavi Kompella Toxicology Division Office of the Executive Director TEXAS COMMISSION ON ENVIRONMENTAL QUALITY Diisopropylamine Page i Table of Contents TABLE OF CONTENTS .............................................................................................................. I LIST OF TABLES ....................................................................................................................... II ACRONYMS AND ABBREVIATIONS ................................................................................... III CHAPTER 1 SUMMARY TABLES ........................................................................................... 1 CHAPTER 2 MAJOR SOURCES AND USES .......................................................................... 4 CHAPTER 3 ACUTE EVALUATION ....................................................................................... 4 acute 3.1 Health-Based Acute ReV and ESL ................................................................................. 4 3.1.1 Physical/Chemical Properties........................................................................................ 4 3.1.2 Key and Supporting Studies ........................................................................................... 5 3.1.2.1 Human Studies ........................................................................................................ 5 3.1.2.2 Animal Studies ........................................................................................................ 5 3.1.2.2.1 Key Animal Study (Zissu 1995) ........................................................................ 5 3.1.2.2.2 Supporting Animal Studies ............................................................................... 6 3.1.2.2.2.1 Thirty-Minute Lethality Study in Rats and Guinea Pigs........................... 6 3.1.2.2.2.2 Two-Hour Lethality Studies ..................................................................... 6 3.1.2.2.2.3 Four-Hour Lethality Study in Rats ........................................................... 7 3.1.2.2.2.4 Lethality Studies in Different Species ...................................................... 7 3.1.2.2.2.5 Respiratory Depression Studies in Mice ................................................... 8 3.1.2.3 Reproductive/Developmental Studies ................................................................... 10 3.1.3 Mode-of-Action (MOA) Analysis and Dose Metric ..................................................... 10 3.1.4 Point of Departure (POD) for Key Study and Critical Effect ...................................... 10 3.1.5 Dosimetric Adjustments ............................................................................................... 10 3.1.5.1 Default Exposure Duration Adjustments .............................................................. 10 3.1.5.2 Default Dosimetric Adjustments from Animal-to-Human Exposure ................... 10 3.1.6 Adjustment of the PODHEC and Application of Uncertainty Factors ........................... 11 3.1.7 Health-Based Acute ReV and acuteESL ......................................................................... 12 3.2 Odor Perception .................................................................................................................. 12 3.3 Vegetation Effects ............................................................................................................... 12 3.4 Short-Term ESL .................................................................................................................. 12 3.5 Acute Inhalation Observed Adverse Effect Level .............................................................. 13 CHAPTER 4 CHRONIC EVALUATION................................................................................ 14 4.1 Non-Carcinogenic Potential ................................................................................................ 14 4.1.1 Physical/Chemical Properties...................................................................................... 14 4.1.2 Key Study - Roloff and Ruecker (1987) ........................................................................ 14 4.1.3 Reproductive/Developmental Studies .......................................................................... 16 4.1.4 Critical Effect and POD for the Key Study .................................................................. 17 Diisopropylamine Page ii 4.1.5 MOA Analysis .............................................................................................................. 17 4.1.6 Dosimetric Adjustments ............................................................................................... 18 4.1.6.1 Default Exposure Duration Adjustments .............................................................. 18 4.1.6.2 Default Dosimetric Adjustments from Animal-to-Human Exposure ................... 18 4.1.7 Adjustment of the PODHEC and Application of Uncertainty Factors ........................... 18 chronic 4.1.8 Health-Based Chronic ReV and ESLthreshold(nc) ..................................................... 19 chronic 4.1.9 Chronic Generic ESLs ( ESLgeneric) for DIPA ....................................................... 20 4.1.9.1 Category/Read-Across Approach ......................................................................... 20 4.1.9.2 Relative Potency Factor (RPF) Approach ............................................................. 21 4.2 Carcinogenic Potential ........................................................................................................ 21 4.2.1 Mutagenicity and Genotoxicity .................................................................................... 21 4.2.2 In Vivo Tests ................................................................................................................. 22 4.2.3 Carcinogenicity ............................................................................................................ 22 4.3 Welfare-Based Chronic ESL .............................................................................................. 22 4.4. Long-Term ESL ................................................................................................................. 22 4.5 Subchronic Inhalation Observed Adverse Effect Levels .................................................... 23 CHAPTER 5 REFERENCES .................................................................................................... 24 APPENDIX A CONSIDERATION OF A CATEGORY/READ-ACROSS APPROACH... 28 A.1 Comparison of Physical/Chemical Properties ................................................................... 28 A.2 Read-Across Approach ...................................................................................................... 29 APPENDIX B CONSIDERATION OF A RELATIVE POTENCY APPROACH BASED ON DBA ....................................................................................................................................... 31 List of Tables a 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 for Diisopropylamine ........................................................... 3 Table 4 Summary of Lethality, Acute and Subacute Inhalation Studies ........................................ 9 acute Table 5 Derivation of the Acute ReV and ESL ....................................................................... 13 Table 6 Group Means of Hematology Data Significantly Different from Controls ..................... 15 Table 7 Incidence of Microscopic Findings in the Nose/Turbinates ............................................ 16 Table 8 Summary of Studies that Evaluated Reproductive Organs .............................................. 17 chronic Table 9 Derivation of the Chronic ReV and ESLthreshold(nc) ................................................... 20 Table 10 Comparison of Physical/Chemical Properties for DIPA, DBA and DEA ..................... 28 Table 11 Summary of Toxicity Data Read Across Approach for DIPA, DBA and DEA ............ 30 chronic Table 12 Calculation of the ESLgeneric for DIPA based on RPF ............................................ 32 Diisopropylamine Page iii Acronyms and Abbreviations Acronyms and Definition Abbreviations ACGIH American Conference of Governmental Industrial Hygienists ATSDR Agency for Toxic Substances and Disease Registry C degrees Celsius BMR benchmark response BW body weight DSD development support document ECHA European Chemicals Agency ESL Effects Screening Level acuteESL acute health-based Effects Screening Level for chemicals meeting minimum database requirements acute ESLgeneric acute health-based Effects Screening Level for chemicals not meeting minimum database requirements acute ESLodor acute odor-based Effects Screening Level acute ESLveg acute vegetation-based Effects Screening Level chronic ESLthreshold(c) chronic health-based Effects Screening Level for threshold dose response cancer effect chronic ESLthreshold(nc) chronic health-based Effects Screening Level for threshold dose response noncancer effects chronic ESLnonthreshold(c) chronic health-based Effects Screening Level for nonthreshold dose response cancer effects chronic ESLnonthreshold(nc) chronic