1. P2 Framework and Sustainable Futures: Designing / Selecting Safer Chemicals Bill Waugh December 3, 2004 Lowell Center for Sustainable Production

2. 2 Chemicals in Commerce Pesticides ~2000 Active Ingredients ( AI) FIFRA requires data Drugs, Cosmetics, Food Additives ~2,000 AI Federal Food, Drug, and Cosmetic Act requires data Industrial Chemicals ~80,000 On TSCA Inventory No specific data requirements for PMNs

3. 3 Challenge: Evaluating Chemicals In The Absence Of Data Under TSCA Congress gives EPA authority to evaluate / regulate new chemicals EPA must complete its review in 90 days Proponents of manufacture of New Chemicals are not required to do any new testing. EPA can require testing EPA reviews about 2,000 PMNs per year

4. 4 P2 Framework Models Phys/Chem Properties: EPI Suite  MP, BP, VP; KOW; WS; KOC; Henry’s law constant Environmental Fate: EPI Suite  AOP; Fish BCF; Biodegradation; Hydrolysis; Removal in WWTP Hazard ECOSAR Aquatic Toxicity OncoLogic - Carcinogenicity PBT Profiler PBT potential Exposure / Risk ChemSTEER Release amounts Worker exposure E-FAST Human Risk: Consumer dermal & inhalation exposure, Human PDRs. Aquatic risk 4

5. 5 R&D Process - Status Quo Chemicals Meeting All the Desired Criteria Will Be Evaluated Based on Additional Criteria: PerformanceAvailabilityCost Market Research Final Product Development PMN Submission Often no toxicity screening until this point

6. 6 Kodak XL: The Business Benefits of Risk Screening Decreased:  Product development costs 13 -100%  Time to market  Generation of chemical waste Increased HS&E contribution Tellus Report: Describes Kodak's experience (Published in BNA Aug. 29, 2001) [Tellus Report 08-25-00.pdf please email waugh.bill@epa.gov for a copy] waugh.bill@epa.gov

7. 7 Kodak XL: Chemical-Specific Case Study (Tellus Report: Appendix B) Saved $750,000-$1,000,000 Reduced time to market by 1.5 to 2 years Reduced generation of chemical waste

8. 8 Kodak XL: Annual Report “Kodak has reviewed materials that were possible candidates for commercialization using the P2 Framework. Of the materials that could have been commercialized, 24% were dropped early in the product development process.” “All PMNs submitted to EPA were cleared by the Agency through their standard review process.”

9. 9 The PBT Profiler PBT Profiler A Component of OPPT’s P2 Framework Assessing Chemicals in the Absence of Data

10. 10 The PBT Profiler Estimates Persistence, Bioconcentration potential, and fish chronic Toxicity from chemical structure

11. 11 PBT Profiler Development Created with input from over 100 beta test participants from industry, academia, and government Developed by EPA as a collaborative effort with industry (ACC, SOCMA, CCC) and NGOs (ED) Underwent formal EPA scientific peer review

12. 12 How Does the PBT Profiler Work? Estimates physical/chemical and fate properties  Persistence: WS, K ow, VP, Henry’s Law constant, OH and O 3 reaction rates, MP, MW, and ultimate biodegradation  Bioaccumulation: BCF  Toxicity: fish chronic value (ChV) from ECOSAR Uses a level 3 multi-media model to estimate distribution in water, soil, sediment, and air Compares P, B, and T estimates to EPA criteria and formats results in color-coded output (Level I) Provides quantitative results (Level II) and additional information for P2 assessments (Level III)

13. 13 P, B & T Criteria > 2 d< 2 d Air > 180 d> 60 d< 60 dWater, soil, sediment PersistentNot Persistent P ersistence > 5,000> 1,000< 1,000Fish BCF Bioaccumulative Not Bioaccumulative B ioaccumulation < 0.1 mg/L 0.1-10 mg/L > 10 mg/L Or No Effects at Saturation Fish ChV (EPA New Chemical Program Criteria) ToxicNot Toxic T oxicity

14. 14 Data Entry – Chemical Information

15. 15 Results for a Non-PBT Chemical Three Tiers of Results are Displayed (3) P2 Information (2) Detailed Results (1) Summary Results

16. 16 PBT Profiler Results – No Criteria Exceeded

17. 17 PBT Profiler Results – All 3 Criteria Exceeded

18. 18 Results – Chemical Categories

19. 19 Results for a PBT Chemical 19

20. 20 Results - No Effects at Saturation

21. 21 Results – Sample Pigment

22. 22 P2 and the PBT Profiler

23. 23 “P2 Considerations” Information to Manage Risk Pollution Prevention (P2) Considerations for “Phenol, 2,4,5-trichloro-” PBT Profiler Estimate = P B T Persistence Summary PartitioningThe PBT Profiler has estimated that if released to the environment, 'Phenol, 2,4,5-trichloro-' is expected to be found predominately in soil. It is also expected to be found in water and sediment. TransformationThe PBT Profiler has estimated that 'Phenol, 2,4,5-trichloro-' is expected to be found predominately in soil and its and persistence estimate is based on its transformation in this medium. Its half-life in soil, 120 days, exceeds the PBT Persistence Profiler criteria of >= 2 months (and <= 6 months). Therefore, 'Phenol, 2,4,5-trichloro-' is estimated to be persistent in the environment. PollutionThe PBT Profiler has estimated that the physical and chemical properties of 'Phenol, 2,4,5-trichloro-' indicate that it Prevention may have the potential to leach through soil and enter groundwater. Considerations Long-Range The PBT Profiler has estimated that 'Phenol, 2,4,5-trichloro-' has a CTD in air of 2,400 Km. Using a published set of Transport criteria, this value is considered relatively high, and 'Phenol, 2,4,5-trichloro-' has the potential to travel long distances (CTD) from its original point of release. Release Scenarios The following table provides the percent estimated in each environmental media using different release scenarios. The color of the estimates indicates if the PBT Profiler criteria have been exceeded in each medium, based on the following estimated half-lives for 'Phenol, 2,4,5-trichloro-': Water 60 days, Soil 120 days, Sediment 540 days, Air 7.5 days Bioaccumulation Summary BioconcentrationThe estimated bioconcentration factor (BCF) for 'Phenol, 2,4,5-trichloro-', 58, does not exceed the PBT Profiler criteria. BioaccumulationThe PBT Profiler estimates that 'Phenol, 2,4,5-trichloro-' is not expected to bioaccumulate in the food chain. Estimate Toxicity Summary Fish Chronic The estimated fish chronic toxicity value (ChV) for 'Phenol, 2,4,5-trichloro-', 0.053 mg/l, exceeds the PBT Profiler Toxicity criteria (<0.1 mg/l). ToxicityThe PBT Profiler estimates that 'Phenol, 2,4,5-trichloro-' is estimated to be toxic to fish. Estimate Release to each Medium (Kg) Percent in each medium AirWaterSoilAirWaterSoilSed 1,000 113842 1,0001 11980 1,00011136801 1,000 1555318 11,000 014842 11,0001086113 111,000001000

24. 24 Why Use the PBT Profiler? Of the 80,000 Chemicals on the TSCA Inventory, the PBT Profiler can profile 2/3rds or more Chemicals That Can Be Profiled (62%) Chemicals That Should Not Be Profiled (38%) [Mixtures can be profiled if a representative structure is identified] 38% 62%

25. 25 Chemicals With Experimental Data Inorganic Chemicals Reactive Chemicals Salts (Organic Salts)  Sodium (Na), Potassium (K), and ammonium (NH 4 +) salts can be Profiled High Molecular Weight Compounds (MW > 1000) Chemicals with Unknown or Variable Composition Mixtures Surfactants Highly Fluorinated Compounds Chemicals That Can Not be Profiled

26. 26 Data Entry – Warning Flags Other flags  Metals  High molecular weight compounds (> 1,000)  Mixtures (representative structure provided)

27. 27 Sample Chemicals to Show PBT Profiler Capabilities PBT Profiler CapabilityCAS Registry # Flag for Metals54-64-8 Flag for chemicals on EPA's PBT list and UNEP's POPs list 35822-46-9 Flag for Mixtures1319-73-9 Results are All Green - no criteria exceeded59-56-3 Results are All Red - all three criteria exceeded8001-35-2 Persistent and bioaccumulative chemical with toxicity not estimated flag on results page 29082-74-4 Link to EPA's Chemical Categories for human health concerns 66736-54-7 Molecular weight > 1,000 flag71216-03-0 Aquatic toxicity is NES - No Effects at Saturation5261-31-4

28. 28 PPG XL: Validation Studies of P2 Framework Methods Comparison of Environmental Fate Data from the PBT Profiler with Data Found in the Literature [PBT Profiler PPG Chlorobenzenes data vs PBT Profiler predictions.pdf] Dr. H. Burleigh-Flayer, PPG Industries, Inc., Pittsburgh, PA. - 90% concordance with measured data

29. 29 Steady Increase Seen in Number of Chemicals Evaluated with PBT Profiler Since Public Release on Sept. 25, 2002 Number of Chemicals Profiled Source: PBT Profiler online model www.pbtprofiler.net “What’s New” page, click on Details to get the number of chemicals profiled by date.www.pbtprofiler.net

30. Analog Identification Methodology (AIM) Beta Test Begins December 2004 Office of Pollution Prevention and Toxics U.S. Environmental Protection Agency

31. 31 AIM Methodology The AIM database contains 31,031 potential analogs with publicly available toxicity data Enter chemical by CAS, SMILES, or Drawing structure Experimental data sources Indexed  On-Line Databases TSCATS, HSDB, IRIS  U.S. Government Documents NTP, ATSDR, HPV Challenge Program  Other Sources DSSTox, RTECS, IUCLID, AEGLS Uses a chemical fragment-based approach with 645 individual chemical fragments to identify potential analogs.

32. 32 AIM Methodology (cont.) Uses a “three-pass” methodology to identify analogs:  Pass 1- Analogs are selected when a match of 645 possible chemical fragments occurs. If less than 7 analogs are identified, then:  Pass 2 - Analogs are selected when a match of 200 fragments occur and allows alkyl substitutions. If less than 7 analogs are identified again, then:  Pass 3 - Allows halogens (chlorine, bromine, or iodine) substitutions. Results from first pass (search) are displayed in numerical order by CAS RN, followed by results from second, then third passes. First analog displayed may not be the closest analog with data.

33. 33 Opening Screen of Internet Based Model About the AIM Methodology

34. 34 The Analog Identification Methodology (AIM) was designed to help identify publicly available, experimental toxicity data on closely related chemical structures. About the AIM Methodology Isodecyl acrylate SMILES Entered Running AIM by Entering SMILES

35. 35 Running AIM by Using Integrated Draw Program Isodecyl acrylate CAS 1330-61-6 Drawn and Entered

36. 36 Results First 6 analogs found for Isodecyl acrylate, #1 is the same chemical

37. 37 Search for Analogs to Butyl acrylate CAS RN 141-32-2 The Analog Identification Methodology (AIM) was designed to help identify publicly available, experimental toxicity data on closely related chemical structures. About the AIM Methodology Butly acrylate CAS 141-32-2 Entered

38. 38 Results Analogs found, #1 is the same chemical

39. 39 Soliciting Beta Test Participants Internet-based, easy to use model Operates on password-protected site For information on AIM or Sustainable Futures contact: To become a participant in the AIM beta test and to set-up access to the website, please contact: Bill Waugh 202-564-7657 waugh.bill@epa.gov waugh.bill@epa.gov Kelly Mayo-Bean 202-564-7662 mayo.kelly@epa.gov mayo.kelly@epa.gov OR Jim Santory 412-751-8958 jsantory@cermonline.com

40. 40 Sustainable Futures Encourages Risk Screening at R&D Sustainable Futures provides 1. Powerful risk screening tools; the P2 Framework and PBT Profiler 2. Training in the use, interpretation and limitations of EPA's screening methods 3. Detailed, one-on-one, technical assistance: P2 Partnerships 4. Regulatory Relief 5.Small Business Assistance Program 6.Public Recognition

41. 41 Agenda DAY 1 Morning Sustainable Futures (SF) Pilot Project Intro. & Background SF Summary Assessment Data Collection and Intro. Information Afternoon EPISuite – P / Chem EPISuite – Fate ECOSAR Open Lab* – Q&A DAY 2 Morning Non-Cancer Human Health Effects OncoLogic Afternoon PBT Profiler ChemSTEER E-FAST DAY 3 Morning Risk Assessment Green Chemistry Wrap-Up Afternoon Open Lab – Q&A 41 * During the Hands-On Sessions and Open Labs you can use the P2 Framework models to screen the example chemicals provided, or chemicals you brought with you.

42. 42 Sustainable Futures Evolved from the PMN Process The Problem for PMN Submitters is Getting New Chemicals to Market R&D Regulation DOA Business Benefits Satisfied Customer $ $$ $ 42 PMN Review ?

43. 43 Sustainable Futures Can Open Up the Black Box R&D Business Benefits Satisfied Customer Sustainable Futures Regulatory ReliefPublic Recognition Health Ecotox Risk 43

44. 44 R&D Process - Status Quo Chemicals Meeting All the Desired Criteria Will Be Evaluated Based on Additional Criteria: PerformanceAvailabilityCost Market Research Final Product Development PMN Submission Often no toxicity screening until this point

45. Sustainable Futures: P2 Partnerships

46. 46 What Are Sustainable Futures P2 Partnerships? Technical assistance in your area of chemistry for Sustainable Futures participants Hands-on; one-on-one instruction and technical assistance No cost to companies, assistance provided through EPA grants Ensure safety of Confidential Business Information

47. 47 Sustainable Futures P2 Partnerships: Purpose Help with the learning curve Provide additional support in use and interpretation of P2 Framework methods Help insure successful participation in Sustainable Futures Hands-on; one-on-one instruction and technical assistance

48. 48 R&D Process - Status Quo Chemicals Meeting All the Desired Criteria Will Be Evaluated Based on Additional Criteria: PerformanceAvailabilityCost Market Research Final Product Development PMN Submission Often no toxicity screening until this point

49. 49 More Information on the P2 Framework Sustainable Futures http://www.epa.gov/opptintr/newchems/sustainablefutures.htm http://www.epa.gov/opptintr/newchems/sustainablefutures.htm P2 Framework and Models Internet sites:  www.epa.gov/oppt/p2framework www.epa.gov/oppt/p2framework  www.pbtprofiler.net www.pbtprofiler.net  www.epa.gov/opptintr/exposure/ www.epa.gov/opptintr/exposure/ www.epa.gov/opptintr/exposure/docs/EPI Suitedl.htm www.epa.gov/opptintr/exposure/docs/efast.htm www.epa.gov/opptintr/exposure/docs/chemsteer.htm Email or call EPA contacts to:  Request workshop information  Ask additional questions Bill Waugh Ph: 202-564-7657 waugh.bill@epa.gov Maggie Wilson Ph: 202-564-8924 wilson.maggie@epa.gov

50. 50 PBT Profiler Results for PentaDBE

51. 51 Bayer’s PBT Profiler Case Study Nine candidate chemicals were evaluated for PBT potential. PersistenceToxicityBioaccum. None exceeded PBT criteria, however, candidates with the most favorable characteristics were commercialized, and problematic chemicals were dropped. PBT Criteria