An Overview of the Objectives, Approach, and Components of ComET™ Mr. Paul Price The LifeLine Group All slides and material Copyright protected

Purpose of ComET™ Tool which uses exposure as the measure to parallel a separate toxicity approach—yielding highest plausible exposure (or risk) measures for substances in consumer products or environmental media. Tool which uses exposure as the measure to parallel a separate toxicity approach—yielding highest plausible exposure (or risk) measures for substances in consumer products or environmental media. Applicable to large number of widely varying substances Applicable to large number of widely varying substances –Low effort per chemical –Can be consistently applied to a wide variety of substances Highlight substances from the many DSL substances to advance for full risk assessment Highlight substances from the many DSL substances to advance for full risk assessment

Purpose of ComET™ Provide a means of identifying substances that offer minimal exposures (and risks) and deserve little further risk-based regulatory attention. Provide a means of identifying substances that offer minimal exposures (and risks) and deserve little further risk-based regulatory attention. Tool which is completely transparent and can be used by all stakeholders. Make effective use of publicly available information on substances. Tool which is completely transparent and can be used by all stakeholders. Make effective use of publicly available information on substances.

General Approach 1 In the same tool, consider exposure from consumer products (near field) and environmental components (far field) In the same tool, consider exposure from consumer products (near field) and environmental components (far field) Use publicly available data- critical to transparency Use publicly available data- critical to transparency For each chemical, estimate the highest plausible exposures that could reasonably be expected to be presented to the public and subgroups of the public from any product or group of products (sentinel products) For each chemical, estimate the highest plausible exposures that could reasonably be expected to be presented to the public and subgroups of the public from any product or group of products (sentinel products) Link environmental exposures to consumer exposure via diet and water Link environmental exposures to consumer exposure via diet and water

General Approach 2 Considering summed exposures from sentinel products and environmental sources for each chemical, chemicals can be Considering summed exposures from sentinel products and environmental sources for each chemical, chemicals can be –Set aside from further consideration, based on comparison with critical toxicity values –Ranked on a relative scale (exposure or risk) Tool is therefore useful to set priorities for: Tool is therefore useful to set priorities for: –Further priority setting or assessment –Highlighting data needs to improve accuracy and reduce overestimation of exposure –Highlight product types thought to be sentinel for the chemical and subpopulations of particular concern

General Approach 3 Identify those substances that are used in at least one consumer product or have an environmental source that results in “relatively” high exposure that occurs: Identify those substances that are used in at least one consumer product or have an environmental source that results in “relatively” high exposure that occurs: –By a specific route –To a specific age group –Over a specific duration of time Make this data available for combination with toxicity information Make this data available for combination with toxicity information Provide multiple summing techniques for easy ranking views Provide multiple summing techniques for easy ranking views

ComET™ is Based on a Quantitative Exposure Modeling Does not rely on surrogates for exposure (use codes or consensus opinions) Does not rely on surrogates for exposure (use codes or consensus opinions) Based on an actual exposure assessment that includes: Based on an actual exposure assessment that includes: –A specific product –A defined exposure scenario –A dose rate calculation Separate determinations for: Separate 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 Future step to extend to risk using compound specific toxicity data

Make Effective Use of Available Information Physical chemical properties of substances Physical chemical properties of substances Use in commercial products Use in commercial products Fugacity based models of far field sources Fugacity based models of far field sources

Transparency Open methodology Open methodology Disclosure of all all assumptions Disclosure of all all assumptions Based on publicly available data Based on publicly available data Use of publicly available data –Process compared to information submitted under cover of confidentiality—favorable comparison –Additional comparison exercises to be conducted to assure all use scenarios are included –In future, additional data sources expected to emerge

Approach Used in ComET™ Based on “Sentinel Product(s)” and environmentally mediated exposures (far field sources) Based on “Sentinel Product(s)” and environmentally mediated exposures (far field sources) Exposure based on a highest plausible exposure resulting from use of a sentinel product Exposure based on a highest plausible exposure resulting from use of a sentinel product Separate determinations of dose resulting: Separate 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 Tool for ranking the substances

Key Concept – The Sentinel Product A product that is available to the general public A product that is available to the general public Does not include: Does not include: –Site limited intermediates –Substances only used in the workplace Does include food additives Does include food additives Contributes highest plausible exposure

The Sentinel Product The Sentinel Product Defined as a product that produces a high level of exposure: Defined as a product that produces a high level of exposure: –to consumers of various ages –by one or more routes Information on product obtained from published sources and the internet (topic of later talk) Information on product obtained from published sources and the internet (topic of later talk) Product are selected based on general principals of exposure 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 Where a substance is used in multiple high exposure potential products then include create multiple sentinel products Where a substance is used in multiple high exposure potential products then include create multiple sentinel products

Process for Evaluating a Substance 1. Gather data—public sources and publicly available private sources 2. Identification of sentinel products using criteria for consideration of exposure characteristics and subpopulations 3. Identification of exposure scenarios 4. Assignment of values for dose rate equations for the sentinel products and each age group 5. Determination of route and duration specific doses for each product and age group 6. Linking exposures from environmental media

Interpreting the Findings of ComET™ 1 Difference between priority setting (ComET™) and a full exposure assessment Difference between priority setting (ComET™) and a full exposure assessment Actual risk assessments will need to assess actual practices (Difference between sentinel product and “representative product”…inference for full array of uses of chemical) Actual risk assessments will need to assess actual practices (Difference between sentinel product and “representative product”…inference for full array of uses of chemical) High levels of exposure in ComET™ indicate that the substances will have at least one consumer product High levels of exposure in ComET™ indicate that the substances will have at least one consumer product

Interpreting the Findings of ComET™ 2 Low levels indicate a limited potential for exposure and suggest a low priority for additional action. Low levels indicate a limited potential for exposure and suggest a low priority for additional action. Highlighting where better data can be developed Highlighting where better data can be developed Ways to interpret relative ranking Ways to interpret relative ranking

Strengths and Limitations Strengths Transparent / accessible / viewed and corrected by all stakeholders and public Transparent / accessible / viewed and corrected by all stakeholders and public Considers differences in subpopulations Considers differences in subpopulations Can conduct sensitivity analysis on chemical’s parameters to highlight areas of opportunity for new data Can conduct sensitivity analysis on chemical’s parameters to highlight areas of opportunity for new data Relative ranking helps to prioritize issues, chemicals, types of products for full risk assessment attention Relative ranking helps to prioritize issues, chemicals, types of products for full risk assessment attention Additional chemicals easily added using stable of sentinel products and exposure scenarios Additional chemicals easily added using stable of sentinel products and exposure scenarios

Strengths and Limitations Limitations Possible underestimation of exposure if sum of non-sentinel products is greater than exposure from sentinel products. Possible underestimation of exposure if sum of non-sentinel products is greater than exposure from sentinel products. Doesn't consider chemical specific limitations on level in products or use patterns. Doesn't consider chemical specific limitations on level in products or use patterns.

Demonstration of the Model The following slides present some key components of ComET™ Details provided in following presentations

Ranking by Route of Exposure

Ranking by Duration of Exposure

Library of Chemicals

Ranking Exposures within Age Groups

Type of Ranking Exercise

Age Specific Factors

Age Specific Factors (Continued)

The DSL Worksheet: Inhalation Exposures

The DSL Worksheet

Process To Date 1. Data gathering—public sources and publicly available private sources 2. Selection of sentinel products using criteria for consideration of exposure characteristics and subpopulations 3. Assignment of values in algorithms appropriate for the sentinel product 4. Application of the metrics to the model

Current Status of the Tool Library of Sentinel Product Scenarios developed currently based on pilot chemicals Library of Sentinel Product Scenarios developed currently based on pilot chemicals However, it is the library rather than the chemicals, themselves, which is important However, it is the library rather than the chemicals, themselves, which is important –Will be developed to ensure coverage of uses of substances on the DSL Current scenarios based on robust consideration of available sources? Current scenarios based on robust consideration of available sources?

Areas for Stakeholder Input Are the substances linked to appropriate sentinel products? 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 levels used as the upper bound of the possible range (default levels of solvents and polymers in products) correct? Data on actual products should be deferred until actual screening and full assessments Data on actual products should be deferred until actual screening and full assessments

ComET™ A Work in Progress Current version includes 39 substances – will be expanded to more than 500 compound from the Maximal List Current version includes 39 substances – will be expanded to more than 500 compound from the Maximal List Additional products available on line this week Additional products available on line this week Next version will include a consideration of toxicity as well as exposures Next version will include a consideration of toxicity as well as exposures Future version will allow users to enter substances to determine how the would rank with the GPE substances Future version will allow users to enter substances to determine how the would rank with the GPE substances