An Overview of the Objectives, An Overview of the Objectives, Approach, and Components of Approach, and Components of

ComET™ComET™

Mr. Paul PriceMr. Paul PriceThe LifeLine GroupThe LifeLine Group

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Purpose of ComET™Purpose of ComET™ Tool which uses exposure as the measure to parallel Tool which uses exposure as the measure to parallel

a separate toxicity approach—yielding highest a separate toxicity approach—yielding highest plausible exposure (or risk) measures for plausible exposure (or risk) measures for substances in consumer products or environmental substances in consumer products or environmental media.media.

Applicable to large number of widely varying Applicable to large number of widely varying substancessubstances– Low effort per chemicalLow effort per chemical– Can be consistently applied to a wide variety of Can be consistently applied to a wide variety of

substances substances

Highlight substances from the many DSL Highlight substances from the many DSL substances to advance for full risk assessment substances to advance for full risk assessment

Purpose of ComET™Purpose of ComET™ Provide a means of identifying Provide a means of identifying

substances that offer minimal substances that offer minimal exposures (and risks) and deserve exposures (and risks) and deserve little further risk-based regulatory little further risk-based regulatory attention.attention.

Tool which is completely transparent Tool which is completely transparent and can be used by all stakeholders. and can be used by all stakeholders. Make effective use of publicly Make effective use of publicly available information on substances.available information on substances.

General Approach General Approach 11

In the same tool, consider exposure from In the same tool, consider exposure from consumer products (near field) and consumer products (near field) and environmental components (far field)environmental components (far field)

Use publicly available data- critical to Use publicly available data- critical to transparencytransparency

For each chemical, estimate the highest For each chemical, estimate the highest plausible exposures that could reasonably plausible exposures that could reasonably be expected to be presented to the public be expected to be presented to the public and subgroups of the public from any and subgroups of the public from any product or group of products (sentinel product or group of products (sentinel products)products)

Link environmental exposures to consumer Link environmental exposures to consumer exposure via diet and waterexposure via diet and water

General Approach General Approach 22

Considering summed exposures from sentinel Considering summed exposures from sentinel products and environmental sources for each products and environmental sources for each chemical, chemicals can bechemical, chemicals can be– Set aside from further consideration, based on Set aside from further consideration, based on

comparison with critical toxicity valuescomparison with critical toxicity values– Ranked on a relative scale (exposure or risk)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 Further priority setting or assessment – Highlighting data needs to improve accuracy Highlighting data needs to improve accuracy

and reduce overestimation of exposureand reduce overestimation of exposure– Highlight product types thought to be sentinel Highlight product types thought to be sentinel

for the chemical and subpopulations of for the chemical and subpopulations of particular concern particular concern

General Approach General Approach 33

Identify those substances that are used in at least Identify those substances that are used in at least one consumer product or have an environmental one consumer product or have an environmental source that results in “relatively” high exposure source that results in “relatively” high exposure that occurs:that occurs:– By a specific route By a specific route – To a specific age groupTo a specific age group– Over a specific duration of timeOver a specific duration of time

Make this data available for combination with Make this data available for combination with toxicity informationtoxicity information

Provide multiple summing techniques for easy Provide multiple summing techniques for easy ranking viewsranking views

ComET™ is Based on a ComET™ is Based on a Quantitative Exposure ModelingQuantitative Exposure Modeling

Does not rely on surrogates for exposure (use Does not rely on surrogates for exposure (use codes or consensus opinions)codes or consensus opinions)

Based on an actual exposure assessment that Based on an actual exposure assessment that includes: includes: – A specific productA specific product– A defined exposure scenarioA defined exposure scenario– A dose rate calculationA dose rate calculation

Separate determinations for:Separate determinations for:– Oral dermal and inhalation dose routesOral dermal and inhalation dose routes– Multiple ages (infants, children, adults , and the elderly)Multiple ages (infants, children, adults , and the elderly)– Acute, subchronic, and chronic durations of exposure Acute, subchronic, and chronic durations of exposure

Future step to extend to risk using compound Future step to extend to risk using compound specific toxicity dataspecific toxicity data

Make Effective Use of Available Make Effective Use of Available InformationInformation

Physical chemical properties of substancesPhysical chemical properties of substances

Use in commercial productsUse in commercial products

Fugacity based models of far field sources Fugacity based models of far field sources

TransparencyTransparency

Open methodologyOpen methodology Disclosure of all all assumptionsDisclosure of all all assumptions Based on publicly available dataBased on publicly available data

Use of publicly available dataUse of publicly available data

– Process compared to information submitted Process compared to information submitted under cover of confidentiality—favorable under cover of confidentiality—favorable comparisoncomparison

– Additional comparison exercises to be conducted Additional comparison exercises to be conducted to assure all use scenarios are includedto assure all use scenarios are included

– In future, additional data sources expected to In future, additional data sources expected to emergeemerge

Approach Used in ComET™ Approach Used in ComET™

Based on “Sentinel Product(s)” and environmentally Based on “Sentinel Product(s)” and environmentally mediated exposures (far field sources)mediated exposures (far field sources)

Exposure based on a Exposure based on a highest plausible exposurehighest plausible exposure resulting from use of a sentinel productresulting from use of a sentinel product

Separate determinations of dose resulting:Separate determinations of dose resulting:– Oral dermal and inhalation dose routesOral dermal and inhalation dose routes– Multiple ages (infants, preschoolers, children, young adults, Multiple ages (infants, preschoolers, children, young adults,

adults, and the elderly)adults, and the elderly)– Acute, subchronic, and chronic durations of exposure Acute, subchronic, and chronic durations of exposure

Tool for ranking the substances Tool for ranking the substances

Key Concept – The Sentinel Key Concept – The Sentinel Product Product

A product that is available to the general public A product that is available to the general public Does Does notnot include: include:

– Site limited intermediatesSite limited intermediates– Substances only used in the workplace Substances only used in the workplace

Does include food additivesDoes include food additives

Contributes highest plausible exposure Contributes highest plausible exposure

The Sentinel ProductThe 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 agesto consumers of various ages– by one or more routesby one or more routes

Information on product obtained from published sources and Information on product obtained from published sources and the internet (topic of later talk) the internet (topic of later talk)

Product are selected based on general principals of exposureProduct are selected based on general principals of exposure– Direct contract is necessary for dermal exposureDirect contract is necessary for dermal exposure– Compounds must be volatile or the product must generate Compounds must be volatile or the product must generate

respirable particlesrespirable particles– Higher concentrations and larger amounts of a substance Higher concentrations and larger amounts of a substance

increase the potential for higher doseincrease the potential for higher dose

Where a substance is used in multiple high exposure Where a substance is used in multiple high exposure potential products then include create multiple sentinel potential products then include create multiple sentinel productsproducts

Process for Evaluating a Process for Evaluating a SubstanceSubstance

1.1. Gather data—public sources and publicly Gather data—public sources and publicly available private sourcesavailable private sources

2.2. Identification of sentinel products using Identification of sentinel products using criteria for consideration of exposure criteria for consideration of exposure characteristics and subpopulationscharacteristics and subpopulations

3.3. Identification of exposure scenarios Identification of exposure scenarios 4.4. Assignment of values for dose rate equations Assignment of values for dose rate equations

for the sentinel products and each age groupfor the sentinel products and each age group5.5. Determination of route and duration specific Determination of route and duration specific

doses for each product and age groupdoses for each product and age group6.6. Linking exposures from environmental mediaLinking exposures from environmental media

Interpreting the Findings of Interpreting the Findings of ComET™ComET™11

Difference between Difference between priority settingpriority setting (ComET™)(ComET™) and a full and a full exposureexposure assessment assessment

Actual risk assessments will need to Actual risk assessments will need to assess actual practices (Difference assess actual practices (Difference between sentinel product and between sentinel product and “representative product”…inference for “representative product”…inference for full array of uses of chemical)full array of uses of chemical)

High levels of exposure in ComET™ High levels of exposure in ComET™ indicate that the substances will have at indicate that the substances will have at least one consumer product least one consumer product

Interpreting the Findings of Interpreting the Findings of ComET™ComET™22

Low levels indicate a limited Low levels indicate a limited potential for exposure and suggest a potential for exposure and suggest a low priority for additional action.low priority for additional action.

Highlighting where better data can Highlighting where better data can be developedbe developed

Ways to interpret relative rankingWays to interpret relative ranking

Strengths and LimitationsStrengths and Limitations

StrengthsStrengths Transparent / accessible / viewed and corrected Transparent / accessible / viewed and corrected

by all stakeholders and publicby all stakeholders and public Considers differences in subpopulationsConsiders differences in subpopulations Can conduct sensitivity analysis on chemical’s Can conduct sensitivity analysis on chemical’s

parameters to highlight areas of opportunity for parameters to highlight areas of opportunity for new datanew data

Relative ranking helps to prioritize issues, Relative ranking helps to prioritize issues, chemicals, types of products for full risk chemicals, types of products for full risk assessment attentionassessment attention

Additional chemicals easily added using stable of Additional chemicals easily added using stable of sentinel products and exposure scenariossentinel products and exposure scenarios

Strengths and LimitationsStrengths and Limitations

LimitationsLimitations Possible underestimation of exposure Possible underestimation of exposure

if sum of non-sentinel products is if sum of non-sentinel products is greater than exposure from sentinel greater than exposure from sentinel products. products.

Doesn't consider chemical specific Doesn't consider chemical specific limitations on level in products or use limitations on level in products or use patterns.patterns.

Demonstration of the ModelDemonstration of the Model

The following slides present some key The following slides present some key components of ComET™components of ComET™

Details provided in following presentationsDetails provided in following presentations

Ranking by Route of ExposureRanking by Route of Exposure

Ranking by Duration of ExposureRanking by Duration of Exposure

Library of ChemicalsLibrary of Chemicals

Ranking Exposures within Age Groups

Type of Ranking Exercise

Age Specific Factors

Age Specific Factors (Continued)

Age Specific Factors (Continued)

The DSL Worksheet: Inhalation Exposures

The DSL Worksheet

The DSL Worksheet

Process To DateProcess To Date

1.1. Data gathering—public sources and Data gathering—public sources and publicly available private sourcespublicly available private sources

2.2. Selection of sentinel products using Selection of sentinel products using criteria for consideration of exposure criteria for consideration of exposure characteristics and subpopulationscharacteristics and subpopulations

3.3. Assignment of values in algorithms Assignment of values in algorithms appropriate for the sentinel productappropriate for the sentinel product

4.4. Application of the metrics to the Application of the metrics to the modelmodel

Current Status of the ToolCurrent Status of the Tool

Library of Sentinel Product Scenarios Library of Sentinel Product Scenarios developed currently based on pilot developed currently based on pilot chemicalschemicals

However, it is the library rather than However, it is the library rather than the chemicals, themselves, which is the chemicals, themselves, which is importantimportant– Will be developed to ensure coverage of Will be developed to ensure coverage of

uses of substances on the DSLuses of substances on the DSL Current scenarios based on robust Current scenarios based on robust

consideration of available sources?consideration of available sources?

Areas for Stakeholder InputAreas for Stakeholder Input

Are the substances linked to appropriate sentinel Are the substances linked to appropriate sentinel products?products?

Are the levels used as the upper bound of the Are the levels used as the upper bound of the possible range (default levels of solvents and possible range (default levels of solvents and polymers in products) correct?polymers in products) correct?

Data on actual products should be deferred until Data on actual products should be deferred until actual screening and full assessments actual screening and full assessments

ComET™ A Work in ProgressComET™ A Work in Progress

Current version includes 39 substances – will be Current version includes 39 substances – will be expanded to more than 500 compound from the expanded to more than 500 compound from the Maximal ListMaximal List

Additional products available on line this weekAdditional products available on line this week

Next version will include a consideration of Next version will include a consideration of toxicity as well as exposures toxicity as well as exposures

Future version will allow users to enter Future version will allow users to enter substances to determine how the would rank with substances to determine how the would rank with the GPE substances the GPE substances