Exposure Assessment Choosing the Right Approach

Transcription

1 Exposure Assessment Choosing the Right Approach Christine F. Chaisson, Ph.D. Director, The LifeLine Group The REACH Conference Experien Health ciences Houston, TX October 26, 2006

2 The LifeLine Group Not-for for-profit organization [ 501(c)(3) ] with mission to: Develop technically excellent tools for characterizing exposures to chemicals in diet, residences, consumer products, and occupational exposures and resulting risk, Make those tools available to all interested parties (distributed free) And support the underlying sciences to these goals.

3 The LifeLine Group oftware Design for Exposure and Risk Assessment Development of Relevant Data Bases and Approaches to Using Them Non-advocacy Advisors to the Users of the oftware and Information (industry, governments, other stakeholders)

4 The Role of Exposure Assessment in the Business of Consumer Product Trade and Chemical Manufacturing Understanding the New Rules, Technical Objectives and Expectations of the Decision Maker Getting the Biggest Bang for the Buck When Investing in the Exposure Assessment Information and Analyses

5 Focus on the New Objectives Keeping ight of the Goal for the ciences Basic focus of REACh Manufacturing Use Disposal Needs of the Regulators Oversight, Prioritizing, Providing Process Needs of the Industry(ies) ) for their products Develop the data, the assessments and use guidance that assures safety in Manufacturing, Use and Disposal scenarios.

6 Two Roles for Exposure Assessment Under the REACh Paradigm Needs of the Regulators Oversight, Prioritizing, Providing Process Needs of the Industry(ies) ) for their products Develop the data, the assessments and use guidance that assures safety in Manufacturing, Use and Disposal scenarios. Registration, Evaluation and Authorization of Chemicals

7 Credits: everal parts of this presentation and some graphics are taken from presentations by Frans M. Christensen and colleagues European Chemicals Bureau, DG JRC, European Commission

8 1. Needs of the Regulator Prioritizing the Review and Focusing Resources At some level, relative ranking will be done Based on: Hazard criteria bright line cutoffs Production Volumes - bright line cutoffs Exposure Potential Continuum perhaps also Risk Potential - Continuum

9 1. Needs of the Regulator Prioritizing the Review and Focusing Resources At some level, relative ranking will be done Based on: Hazard criteria bright line cutoffs Production Volumes - bright line cutoffs Exposure Potential Continuum perhaps also Risk Potential - Continuum

10 Concepts for Relative Ranking RIP 4.3 approach being developed by ECB (Frans Christensen and colleagues) Probable highlights: entinel product approach Use of easily accessible data or assumed defaults Integrates all routes of exposure, all sources within the category of the product and chemical use

11 Precedent: Only comparable approach is with Health Canada s s implementation of Canadian Environmental Protection Act of 1996 implemented ept Used ComET as an exposure-based ranking tool.

12 ComET is Based on a Quantitative Exposure Modeling Does not rely on surrogates for exposure (use codes or consensus opinions) Based on an actual exposure assessment that includes: A specific product A defined exposure scenario A dose rate calculation eparate determinations for: Oral dermal and inhalation dose routes Multiple ages (infants, children, adults, and the elderly) Acute, subchronic, and chronic durations of exposure Future step to extend to risk using compound specific toxicity data

13 Approach Used in ComET Based on entinel Product(s) and Based on and environmentally mediated exposures (far field sources) Exposure based on a highest plausible exposure resulting from use of a sentinel product eparate determinations of dose resulting: Oral dermal and inhalation dose routes Multiple ages (infants, preschoolers, children, young adults, adults, and the elderly) Acute, subchronic, and chronic durations of exposure Tool for ranking the substances

14 The entinel Product Defined as a product that produces a high level of exposure: to consumers of various ages by one or more routes Product are selected based on general principals of exposure Direct contract is necessary for dermal exposure Compounds must be volatile or the product must generate respirable particles Higher concentrations and larger amounts of a substance increase the potential for higher dose If substance used in multiple high exposure potential products then include multiple sentinel products

15 Interpreting the Findings of ComET Difference between priority setting (ComET ) ) and a representative exposure assessment Actual risk assessments will need to assess actual practices (Difference between sentinel product and representative product )

16 Interpreting the Findings of ComET Low levels indicate a limited potential for exposure and suggest a low priority for additional action. Highlighting where better data can be developed

17 Ranking by Route of Exposure

18 Ranking by Duration of Exposure

19 Library of Chemicals

20 Ranking Exposures within Age Groups

21 Type of Ranking Exercise

22 Age pecific Factors

23 Areas for takeholder Input Are the substances linked to appropriate sentinel products? Are the levels used as the upper bound of the possible range (default levels of solvents and polymers in products) correct? Are the defaults representative and relative or should new data and algorithms be developed.

24 Precedents and Lessons Learned entinel Product approach is useful to focus attention on hi-exposure exposure scenarios and/or data voids where only assumptions/defaults are being used. Better Data = Lower Ranking Result

25 Precedents and Lessons Learned Can show what assumptions, factors and algorithms DRIVE the exposure assessment.!! Focus your Resources HERE!! Can show what level of precision is needed in exposure studies Most Lucrative Products = or = Place to pend Your Money

26 2. Needs of the Industry for their products Representative Exposure Assessments for All Key Exposure cenarios for the MUD All routes of exposure All sources of exposure Nearfield and Farfield Age groups relevant to Tox metrics Multiple durations of Exposure considered

27 Exposure cenario (E) An exposure scenario sets out, for a given use, how the substance can be used in a way that risks are adequately controlled by describing: Conditions for use: Process descriptions (incl. quantity used) Operational conditions (incl. frequency and duration of specified operations) Risk Management Measures (process and emission control, personal protective equipment, good hygiene, etc.) Other relevant information

28 Chemical afety Assessment Existing knowledge/data Revise assumed RMM and/or operational conditions Exposure scenarios Exposure assessment Classification and labelling Hazard identification Hazard assessment NO Risk characterisation Are risks adequately controlled? YE NO Es with RMM and operational conditions to adequately control the risks, to be: - Documented in the Chemical afety Report (CR) - Communicated to downstream users via an D annex

29 Chemical life cycle Manufacturer/Importer Manufacture Own Use Value chain On Market Professional use P 1 P 2 P 1 P 2 A 1 A 2 A 1 A 2 DisposalDisposal P A ubstance Preparation Article Consumer use P 1 P 2 A 1 A 2

30 Communication upplier D including Exposure cenarios (Recommended Risk Management Measures) afety Data heet Partners in Developing Exposure Information pecific tarting use With Defining Exposure cenarios Downstream user(s)

31 IUCLID 5 cope: Collecting & submitting information on substances for all actors: Industry: pre-registration/registration/application registration/registration/application for authorisations Agency & M: Annex XIV dossiers, Dossier and substance evaluation and all regulatory programmes: : EC, OECD, U-EPA, etc.

32 LifeLine: completed analysis of three software programs: Probabilistic Methodology for Improving cenario-driven Exposure Assessment (PROMIE ) Version 7 Consumer Exposure Model (ConsExpo) Version 4 beta Multi-Chamber Concentration and Exposure Model (MCCEM) Version 2.4

33 The goals of this work: 1. Assess and compare the relative strengths and weaknesses of these tools; 2. Determine the areas of scenario-based exposure assessment that are currently not well addressed in these models; 3. Develop a list of suggested improvements to the PROMIE and ConsExpo Model; 4. Review the programming platform for PROMIE; and 5. Identify relevant and germane elements of PROMIE and MCCEM that are currently missing in ConsExpo.

34 GRADE Key: for defined tasks A - Well designed and suited to perform B - Present or reasonably competent C - Doable with difficulty or poorly achieved D - Not present

35 PROMIE ConsExpo MCCEM 1 The ability to perform screening level assessments (using many conservative assumptions) B A B 2 The ability to perform refined exposure assessments (incorporate additional product- and scenario- specific data e.g., adsorption sinks) A C- B 3 The ability to include detailed human activity patterns (placing people in and out of exposure fields) D D A 4 Ability to Do Aggregate Exposure (can do Dermal and Oral as well as Inhalation Exposure with any scenario) A B D

36 PROMIE ConsExpo MCCEM 5 Includes conservation of mass (so that more material cannot become airborne than is present in the scenario) B C C 6 The ability to perform sophisticated physiological uptake estimates A D D 7 The ability to define different measures of exposure (theoretical upper bounds, reasonable maximal exposures, select percentiles of the population, and typical exposures) A B C 8 The ability to define exposure time frame (acute as well as chronic exposures) C C A

37 PROMIE ConsExpo MCCEM 9 Ease of Use (intuitive operation and interpretation of outputs) C A B 10 Transparency and Documentation of the model (to the user) C C C 11 Ability to Export Results to Other Formats (output tables to Excel or Access) B D A 12 Guidance in electing and Assigning Default Values and sub models (help for the more casual user) B C C

38 Which Tool to UE?? No existing tool can meet all needs, and those needs will continue to grow, Other tools emerging or adapting LifeLine oftware, expanded for REACh Industry Issue not likely to be any one tool or any centrally sanctioned exposure software.o.o.

39 Messages to Remember Good Exposure Assessment DATA, ALGORITHM, OFTWARE is the secret to success under REACh There are 2 Masters: Relative Ranking for the Regulator Representative Assessment for the pecific ubstance ERVE BOTH MATER!!

40 Messages to Remember Tools can INFORM you Consider what new data to develop when to accept defaults Be the first to know where your chemical will fall in the ranking, And what factors DRIVE the answers.

41 Thanks, and good luck, Contributions from: Christine Chaisson Michael Jayjock usan Arnold Paul Price The LifeLine Group