Chemical Prioritization, Development of Hazard Profiles, and Other Anticipated Uses of the HPV Challenge Data

1. Chemical Prioritization, Development of Hazard Profiles, and Other Anticipated Uses of the HPV Challenge Data Philip Sayre, Ph.D. Risk Assessment Division Office of Pollution Prevention and Toxics U.S. EPA (Washington, DC) sayre.phil@epa.gov

2. HPV Submissions • Single chemical or Chemical Categories • Chemical analog data often used to fill data gaps • Test Plan • Category Definition & Justification (if applicable) • Analog Justification (if applicable) • Physicochemical Properties • Environmental Fate • Health Effects • Ecological Effects • Robust Summaries • Summaries of tests conducted and results

3. EPA HPV Challenge, and OECD SIDS • Single chemical or Category • Chemical analog data often used to fill data gaps • Approximately 80% of HPV Challenge chemicals are in Categories • OECD SIDS Endpoint data on approximately 800 HPV Challenge chemicals @ http://www.epa.gov/hpvis/ • Data on over 500 OECD SIDS HPVs is available http://cs3-hq.oecd.org/scripts/hpv/ • Test Plan & Analog Justifications (if applicable) • Category Guidance (http://www.oecd.org or http://www.epa.gov/chemrtk/)

4. A Category may be based on… • A common functional group (e.g., aldehyde, epoxide, ester, etc.) • The likelihood of common precursors and/or breakdown products (e.g., acid/ester/salt) • An incremental and constant change across the category (e.g., CH2 for alpha olefins) • A series of chemical reaction products/mixtures (e.g., petroleum streams, surfactant mixtures)

5. Types of Categories • Traditional • Common functional group • Incremental change in chain length • Production streams • Petroleum products • Sequential change in composition • Mixture families • Family of similar substances

6. Screening Information Data SetSIDS • Physicochemical properties: melting & boiling pts., vapor pressure, water solubility, partition coefficient • Environmental fate: photodegradation, stability in water, biodegradation, transport (model) • Environmental effects: acute toxicity in fish, aquatic invertebrates and aquatic plants • Health effects: acute and subchronic toxicity, genetic toxicity, reproductive and developmental toxicity

7. NPPTACNational Pollution Prevention and Toxics Advisory Committee • Provided advice & recommendations on overall policy and operations of EPA OPPT • Developed hazard-based guidance for prioritizing HPV chemicals for further review • Based on International Globally Harmonized System (GHS) Criteria

8. Hazard CharacterizationTier 1 Screening • Tier 1 Screening placed each HPV chemical into a Review Group (1-3) that determines priority for hazard review & characterization • Review Group 1 – Highest Priority • Review Group 3 – Lowest Priority • Screen Based on: • Human Health Effects • Environmental Effects (Ecotoxicity) • Modified by: Environmental Fate Criteria • Final group assignment is the highest rank achieved for any or all endpoints

9. Endpoints: Repeat Dose Toxicity (primary), Genetic toxicity (both gene mutation and chromosomal aberration), Reproductive toxicity, Developmental toxicity Step 1 – Apply Globally Harmonized System (GHS) criteria to Repeated Dose Toxicity LOAEL Review Group 1: GHS Category 1 Review Group 2: GHS Category 2 Review Group 3: Does not meet GHS Category 2 criteria Step 2 – Modifying Factor 1: Reproductive and Developmental Toxicity Upgrade the chemical to next higher group if: the reproductive or developmental effect is observed at much lower doses than the repeat dose effect for a chemical that is placed in review Group 3 in Step 1 either the reproductive or developmental LOAEL is within the range of the GHS Category 1 criteria, the chemical is upgraded into the review Group 1 for human health. Step 3 – Modifying Factor 2: For chemicals placed in Group 2 or Group 3 in Steps 1 and 2, if one or more endpoints among genetic, reproductive, or developmental toxicity are positive, the chemical is upgraded into the next highest review group. Hazard CharacterizationTier 1 Screening – Human Health

10. Hazard CharacterizationTier 1 Screening – Ecotoxicity Criteria • Endpoints: Acute fish, acute daphnia, and algal toxicity (three different endpoints). • Use GHS criteria for LC50 or EC50: • Group 1: < 1 mg/L • Group 2: 1 – 10 mg/L • Group 3: > 10 mg/L

11. Hazard CharacterizationTier 1 Screening – Environmental Fate Criteria • Endpoints: Log Kow and OECD ready biodegradation test. • Log Kow : >4 (based on GHS) • Ready Biodegradation (based on OECD Test): • Pass > 60% in 28-days • Fail < 60% in 28-days • Environmental fate can modify the placement of a chemical in Group 2 or 3 that resulted from applying the human health or ecotoxicity criteria: • exceed either of the environmental fate criteria – placement one group “higher” • If a chemical preliminarily placed in Group 3 exceeds the criteria for both of the environmental fate endpoints, EPA will consider the final group assignment for the chemical on a case-by-case basis.

12. OPPT HPV Chemical Screening & Characterization Process NEXT STEPS • TIER 1: Sort for Order of Review • Groups 1(30%), 2 (15%) and 3 (18%) • Current Outputs: • Test plan reviews • Data availability – HPVIS • Options to fill Data Needs • Hazard • Exposure • Further Risk Characterization • Determine Whether Chemical is under Review Elsewhere • Refer to other EPA Office, Agency, etc. • Risk Reduction/Pollution Prevention Actions • Other TIER 2: Hazard Characterization Begin Characterization Phase Single Chemicals Categories: Category Analysis • Hazard Characterization Phase • Verify Group Placement & Data • Conduct Hazard Characterization • Identify Data Gaps • Post Completed Screening Level Hazard Characterizations Confounding issues • Complex Class 2 Category • EPA Disagrees with Category Analysis Voluntary/Regulatory Action to Collect/ Share Information • Risk Screening/Characterization Phase • Planning and Scoping • Evaluate Use and Exposure Potential • Conduct Risk Characterization • Determine Data Needs • Post Completed Screening Level Risk Characterizations No Further Action Based on Findings Post to Public Voluntary / Regulatory Action to Manage Risk • Use & Exposure Information • 2006 IUR • Other Sources

13. Development of Tier 2 Screening-level Hazard Characterization Purpose • Conduct a more in-depth scientific/critical review of the data (quality and completeness) with main focus on potential hazard • Develop a screening-level hazard characterization • Does not make determination about risk to human health or environment, but may make recommendations for further post-Tier II work • Inform sponsors and public by posting Tier 2 assessments on the website and in HPVIS

14. An Example OECD HPV Category

15. Conclusions for Several Health Endpoints

16. Hazard Characterization Conclusions, as Illustrated by Selected Recommendations from the Persulfates SIDS Case

17. OPPT HPV Chemical Screening & Characterization Process NEXT STEPS • TIER 1: Sort for Order of Review • Groups 1(30%), 2 (15%) and 3 (18%) • Current Outputs: • Test plan reviews • Data availability – HPVIS • Options to fill Data Needs • Hazard • Exposure • Further Risk Characterization • Determine Whether Chemical is under Review Elsewhere • Refer to other EPA Office, Agency, etc. • Risk Reduction/Pollution Prevention Actions • Other TIER 2: Hazard Characterization Begin Characterization Phase Single Chemicals Categories: Category Analysis • Hazard Characterization Phase • Verify Group Placement & Data • Conduct Hazard Characterization • Identify Data Gaps • Post Completed Screening Level Hazard Characterizations Confounding issues • Complex Class 2 Category • EPA Disagrees with Category Analysis Voluntary/Regulatory Action to Collect/ Share Information • Risk Screening/Characterization Phase • Planning and Scoping • Evaluate Use and Exposure Potential • Conduct Risk Characterization • Determine Data Needs • Post Completed Screening Level Risk Characterizations No Further Action Based on Findings Post to Public Voluntary / Regulatory Action to Manage Risk • Use & Exposure Information • 2006 IUR • Other Sources

18. Post-Tier 2 Activities Follow-up actions addressed during the Planning and Scoping portion of Risk Screening include the following: • Evaluate exposure information obtained under Inventory Update Rule which can inform the need for additional exposure information • Identify hazard data needs, based on hazard and exposure considerations • Identify need for consideration of early risk reduction steps • Indicate need for further risk characterization • Provide information/recommendations for referral to other EPA program offices or Federal agencies

19. IUR Information Considered in the Risk Characterization Stage For chemicals produced at amounts greater than or equal to 25,000 pounds per site per year: -- Manufactured Production Volume per chemical -- Number of Workers Potentially Exposed per chemical For chemicals produced at amounts greater than or equal to 300,000 pounds per site per year: • Primary uses (Industrial Function Categories) • Examples: Adhesives, lubricants, solvents for cleaning (30 categories) • Chemicals used in Commercial & Consumer Products • Examples: Artists’ supplies, non-pesticidal lawn & garden products, soaps and detergents (20 categories) • Chemicals used in Children’s Products

20. Next Steps • Goals for 2007 • Produce several hundred hazard characterizations by the end of 2007 • Internal Review of Draft Hazard Characterizations • Dissemination • Post Hazard Characterizations to the HPV web pages • Opportunity for feedback from Stakeholders on Hazard Characterizations • Begin Incorporation of IUR exposure/use information to produce screening level risk characterizations • Goals for Beyond 2007 • Develop hazard characterizations for all HPV Challenge chemicals over the next three years • Continue development of screening level risk characterizations, and identifying and prioritizing next steps for HPV Challenge chemicals