Supporting Information for Low-Priority Substance Propanedioic Acid, 1,3-Diethyl Ester (CASRN 105-53-3) (Diethyl Malonate) Final Designation February 20, 2020 Office of Pollution Prevention and Toxics U.S. Environmental Protection Agency 1200 Pennsylvania Avenue Washington, DC 20460 Contents 1. Introduction ................................................................................................................................................................ 1 2. Background on Diethyl Malonate ............................................................................................................................. 3 3. Physical-Chemical Properties ................................................................................................................................... 4 3.1 References ....................................................................................................................................................... 6 4. Relevant Assessment History ................................................................................................................................... 8 5. Conditions of Use ....................................................................................................................................................... 9 6. Hazard Characterization .......................................................................................................................................... 12 6.1 Human Health Hazard ................................................................................................................................... 15 6.1.1 Absorption, Distribution, Metabolism, and Excretion .................................................................... 16 6.1.2 Acute Toxicity ................................................................................................................................ 17 6.1.3 Repeated Dose Toxicity ................................................................................................................ 17 6.1.4 Reproductive and Developmental Toxicity.................................................................................... 18 6.1.5 Genotoxicity .................................................................................................................................. 19 6.1.6 Carcinogenicity ............................................................................................................................. 19 6.1.7 Neurotoxicity ................................................................................................................................. 20 6.1.8 Skin Sensitization .......................................................................................................................... 21 6.1.9 Respiratory Sensitization .............................................................................................................. 21 6.1.10 Immunotoxicity .............................................................................................................................. 21 6.1.11 Skin Irritation ................................................................................................................................. 22 6.1.12 Eye Irritation .................................................................................................................................. 22 6.1.13 Hazards to Potentially Exposed or Susceptible Subpopulations .................................................. 22 6.2 Environmental Hazard ................................................................................................................................... 22 6.2.1 Acute Aquatic Toxicity ................................................................................................................... 23 6.2.2 Chronic Aquatic Toxicity ............................................................................................................... 23 6.3 Persistence and Bioaccumulation Potential ................................................................................................... 23 6.3.1 Persistence ................................................................................................................................... 23 6.3.2 Bioaccumulation Potential ............................................................................................................. 23 i 7. Exposure Characterization ...................................................................................................................................... 25 7.1 Production Volume Information ..................................................................................................................... 25 7.2 Exposures to the Environment ....................................................................................................................... 25 7.3 Exposures to the General Population ............................................................................................................ 26 7.4 Exposures to Potentially Exposed or Susceptible Subpopulations ................................................................ 26 7.4.1 Exposures to Workers ................................................................................................................... 26 7.4.2 Exposures to Consumers .............................................................................................................. 26 8. Summary of Findings ............................................................................................................................................... 28 8.1 Hazard and Exposure Potential of the Chemical Substance ......................................................................... 28 8.2 Persistence and Bioaccumulation .................................................................................................................. 30 8.3 Potentially Exposed or Susceptible Subpopulations ...................................................................................... 30 8.4 Storage near Significant Sources of Drinking Water ..................................................................................... 31 8.5 Conditions of Use or Significant Changes in Conditions of Use of the Chemical Substance ........................ 32 8.6 The Volume or Significant Changes in Volume of the Chemical Substance Manufactured or Processed .... 32 8.7 Other Considerations ..................................................................................................................................... 33 9. Final Designation .............................................................................................................................................................. 34 Appendix A: Conditions of Use Characterization ................................................................................................................. I A.1 CDR Manufacturers and Production Volume .......................................................................................................... I A.2. Uses ...................................................................................................................................................................... II A.2.1 Methods for Uses ............................................................................................................................ II A.2.2 Uses of Diethyl Malonate ............................................................................................................... IV A.3 References ........................................................................................................................................................... XII Appendix B: Hazard Characterization ................................................................................................................................ XV B.1 References: .................................................................................................................................................... XXVIII Appendix C: Literature Search Outcomes ....................................................................................................................... XXX C.1 Literature Search and Review .......................................................................................................................... XXX C.1.1 Search for Analog Data .............................................................................................................. XXX C.1.2 Search Terms and Results ....................................................................................................... XXXI C.2 Excluded Studies and Rationale .................................................................................................................... XXXIX C.2.1 Human Health Hazard Excluded References ......................................................................... XXXIX C.2.2 Environmental Hazard ............................................................................................................... XLV ii C.2.3 Fate......................................................................................................................................... XLVIII iii Tables Table 1: Diethyl Malonate at a Glance …………………………………………………………………………………… 3 Table 2: Physical-Chemical Properties for Diethyl Malonate ………………………………………………………… 4 Table 3: Conditions of Use for Diethyl Malonate ……………………………………………………………………… 10 Table 4: Low-Concern Criteria for Human