Concept and Construction of theConcept and Construction of the

“ “Sentinel Product Functions” Sentinel Product Functions”

Criteria and Information SourcesCriteria and Information Sources

Dr. Christine ChaissonDr. Christine ChaissonThe LifeLine GroupThe LifeLine Group

Slides and Materials

Copyright Protected

Sentinel Product Functions (SPF):Sentinel Product Functions (SPF): The Heart of ComET™ The Heart of ComET™

ComET™ is designed to highlight the highest ComET™ is designed to highlight the highest plausible exposure scenarios that could be plausible exposure scenarios that could be presented to subgroups of the population presented to subgroups of the population as a consequence of the use of a as a consequence of the use of a substance in a consumer product.substance in a consumer product.

And…And…The highest plausible exposure profile for The highest plausible exposure profile for

the substance is defined as the sum of the the substance is defined as the sum of the exposures presented by all SPF’s for that exposures presented by all SPF’s for that substance. [via all routes or specific substance. [via all routes or specific routes]routes]

Sentinel Product Functions (SPF):Sentinel Product Functions (SPF): The Heart of ComET™ The Heart of ComET™

The highest plausible exposure profile for The highest plausible exposure profile for the substance is defined as the sum of the the substance is defined as the sum of the exposures presented by all SPF’s for that exposures presented by all SPF’s for that

substance. [via all routes or specific substance. [via all routes or specific routes]routes]

This will be defined by the scenario of USE This will be defined by the scenario of USE

of that type of product…of that type of product…

ANDAND

USE will be variable across subpopulationsUSE will be variable across subpopulations

ComET™ vs. Full Exposure Assessment ComET™ vs. Full Exposure Assessment

ModelsModels ComET™ComET™ Full Exposure Assessment Full Exposure Assessment

ModelsModels operates with minimum of data on operates with minimum of data on specific chemicals specific chemicals Displays Displays highest plausible exposurehighest plausible exposure scenarios from array of products scenarios from array of products possible from the substance possible from the substance Addresses TYPES of products with Addresses TYPES of products with common use scenarios—NOT specific common use scenarios—NOT specific brands brands May overstate exposure, but in May overstate exposure, but in priority setting justifies setting priority setting justifies setting substances aside from further substances aside from further consideration or additional consideration or additional assessmentassessment

requires more data-rich situations for requires more data-rich situations for each chemical each chemical Displays Displays representative exposure representative exposure for for all or some product-specific scenariosall or some product-specific scenariosAddresses specific product brands Addresses specific product brands with brand-specific informationwith brand-specific informationIntent to display exact exposure at a Intent to display exact exposure at a given point (average, 95given point (average, 95thth percentile, percentile, etc) or a full distribution of the etc) or a full distribution of the exposures across the subject exposures across the subject populationpopulation

Portraying highest plausible exposure Portraying highest plausible exposure elements elements

for a for a typetype of product of product

Example: personal care product Example: personal care product

Multiple brands of same type of product: each with different concentration of substance ranging from 0.5 %to 15%

Brand with 15% concentration of subject substance selected for sentinel product values

15%

10%

7% 15%

Selecting the Sentinel Product(s)Selecting the Sentinel Product(s)11

Definition of “Sentinel Product”Definition of “Sentinel Product”– Not the “representative product”Not the “representative product”– A type of product—not brand of productA type of product—not brand of product– Illustrates the general category of product Illustrates the general category of product

in terms of manufacturing, design and usein terms of manufacturing, design and use Elements of ConcernElements of Concern

– Subpopulations: differences in terms of Subpopulations: differences in terms of route of exposure, duration of exposure, route of exposure, duration of exposure, magnitude of exposuremagnitude of exposure

Subpopulations to be Subpopulations to be ConsideredConsideredUSE of a type of product will vary across sub-populationsUSE of a type of product will vary across sub-populations

Factors relevant to exposure will vary across sub-populationsFactors relevant to exposure will vary across sub-populations

0-<0.5 years

0.5 - <5 years

5 - <12 years

12-<20 years

20-59 years

60+ years

Food Intake

Inhalation Rates

Surface Areas

whole body

hands, legs, feet, etc.

Water intake

Soil ingestion, adherence

Body Weight

Example: Population Example: Population DifferencesDifferencesConsider USE profile in terms of frequency, duration, magnitudeConsider USE profile in terms of frequency, duration, magnitude

Consider routes of exposure, etc.Consider routes of exposure, etc.

0-<0.5 years

0.5 - <5 years

5 - <12 years

12-<20 years

20-59 years

60+ years

Food Intake

Inhalation Rates

Surface Areas

whole body

hands, legs, feet, etc.

Water intake

Soil ingestion, adherence

Body Weight

Product types

Baby powder

Make-up

Shampoo

Food additives

Motor Oil

Carpet materials

Material softeners

Selecting the Sentinel Product(s)Selecting the Sentinel Product(s)22

Multiple sentinel products may be Multiple sentinel products may be chosen for a given chemical chosen for a given chemical – Age groupsAge groups– Duration/frequency/periodicity of Duration/frequency/periodicity of

exposureexposure– Magnitude of exposureMagnitude of exposure

See ComET™ Documentation: Sentinel See ComET™ Documentation: Sentinel Product Functions, Draft TaxonomyProduct Functions, Draft Taxonomy

Library of Sentinel Product Functions with Algorithms

Present Limited Library of SPFs and Algorithms

Evolved Library of SPFs and Algorithms Covering

Most/All Substances

SPF: Personal Care

Algorithms:……

………………….SPF: Food

Algorithms…….

>>>>>>>>>>>

Information GatheringInformation GatheringObjectives:Objectives:

– Stock ComET™ with information about types of Stock ComET™ with information about types of products sufficiently representative for Existing products sufficiently representative for Existing Chemicals (the DSL)Chemicals (the DSL)

– To extent possible, make the information and the To extent possible, make the information and the algorithms that apply the information algorithms that apply the information TRANSPARENTTRANSPARENT Confidence of the public and stakeholders Confidence of the public and stakeholders Scrutiny improves performanceScrutiny improves performance Invites submission of better informationInvites submission of better information

– Regarding choice of sentinel productsRegarding choice of sentinel products– Regarding algorithms usedRegarding algorithms used– Regarding values applied to algorithmsRegarding values applied to algorithms

– Submission of information leading to refined Submission of information leading to refined scenarios leading to lower priority for further scenarios leading to lower priority for further workwork

Options for Information Options for Information GatheringGathering

Publicly available data:Publicly available data: Aids transparency of/public confidence in Aids transparency of/public confidence in

ComET™ComET™ Necessary information available?Necessary information available? New and better sources of information becoming New and better sources of information becoming

available over timeavailable over time

Industry-submitted confidential information:Industry-submitted confidential information: Useful for QA checks on ComET™Useful for QA checks on ComET™ Not transparent, not helpful to attract better Not transparent, not helpful to attract better

information or for building public confidence.information or for building public confidence.

Using Publicly Available Information Using Publicly Available Information Sources: Efficacy and AdequacySources: Efficacy and Adequacy

Existing Process Checked for Efficacy and Existing Process Checked for Efficacy and Adequacy: Information Content ExerciseAdequacy: Information Content Exercise

Public Information sought by “naïve” researcher”Public Information sought by “naïve” researcher” Development of search strategies and collection of key Development of search strategies and collection of key

web sites as process evolved.web sites as process evolved. Results compared to information already available to Results compared to information already available to

HC staff “experienced” researcher—including CBI HC staff “experienced” researcher—including CBI submitted by industry. (comparison made by HC submitted by industry. (comparison made by HC scientists)scientists)

Overview of Findings from Overview of Findings from StudyStudy

Favorable resultsFavorable results….….public sources are public sources are adequateadequate and and availableavailable

Search Strategy Guide is an important documentSearch Strategy Guide is an important document– Accrual of valuable web sites and guidance for using the Accrual of valuable web sites and guidance for using the

sites sites – Use of CAS, common names, product category names, etc.Use of CAS, common names, product category names, etc.– New and better sources becoming available, for exampleNew and better sources becoming available, for example

ExpoFacts– European Exposure Factors SourcebookExpoFacts– European Exposure Factors Sourcebook– www.ktl.fi/expofactswww.ktl.fi/expofacts

Some substances present unique challengesSome substances present unique challenges– Ubiquitous substances with many, many uses (copper)Ubiquitous substances with many, many uses (copper)– Monomers, components of polymers (residue Monomers, components of polymers (residue

concentrations in final products)concentrations in final products)– Physical/Chemical Properties of UVCB’sPhysical/Chemical Properties of UVCB’s

Transparency in Application of Transparency in Application of Publicly Available DataPublicly Available Data

Data sources and compendium of data recovered for each Data sources and compendium of data recovered for each chemical can be filed and updated electronically. chemical can be filed and updated electronically.

Summary sheets for each chemical includes metrics Summary sheets for each chemical includes metrics extracted for application to model’s algorithmsextracted for application to model’s algorithms

Transparency of all this useful for all stakeholders to Transparency of all this useful for all stakeholders to identify:identify:– Choice of impossible sentinel productChoice of impossible sentinel product– Missing sentinel productMissing sentinel product– Assignment of metrics not possible for sentinel product Assignment of metrics not possible for sentinel product – Scenarios where sum of exposures from non-sentinel Scenarios where sum of exposures from non-sentinel

products could possibly be greater than exposures from products could possibly be greater than exposures from sum of sentinel products. Is this more probable where sum of sentinel products. Is this more probable where the chemical has many uses?the chemical has many uses?

– Level of uncertainty in the exposure estimates. Level of uncertainty in the exposure estimates. Qualitative notation is made for each metric where Qualitative notation is made for each metric where defaults and overestimation was applied because of defaults and overestimation was applied because of paucity of informationpaucity of information

Assuring Adequacy of Use of Publicly Assuring Adequacy of Use of Publicly Available Information Sources for Available Information Sources for

ComET™ComET™

Going forward—improving the process, Going forward—improving the process, sharing experience with userssharing experience with users– Upgrading the Search Strategy DocumentsUpgrading the Search Strategy Documents– Incorporating New Information Submitted to Incorporating New Information Submitted to

LLG/HC-EC for use in ComET™LLG/HC-EC for use in ComET™– Continued upgrading of all documentation Continued upgrading of all documentation

consistent with additions to ComET™consistent with additions to ComET™ Sentinel Product Functions TaxonomySentinel Product Functions Taxonomy Master DSL Scenario ListMaster DSL Scenario List SPF Algorithm ScenariosSPF Algorithm Scenarios

Assuring Adequacy of Use of Publicly Assuring Adequacy of Use of Publicly Available Information Sources for Available Information Sources for

ComET™ComET™

Going forward---assuring all chemical use Going forward---assuring all chemical use categories can be identifiedcategories can be identified

1.1. Formal screen to assure all known uses of Formal screen to assure all known uses of existing DSL substances are represented by full existing DSL substances are represented by full library of Sentinel Product Functions. This study library of Sentinel Product Functions. This study and its results should be documented as a and its results should be documented as a quality control report.quality control report.

1.1. ComET™ and its documentation will be ComET™ and its documentation will be periodically reviewed for quality. Operational periodically reviewed for quality. Operational experience will be considered. experience will be considered.

Submitting additional informationSubmitting additional information for use in ComET™ for use in ComET™

Information to improve the knowledge Information to improve the knowledge base for the sentinel products , is base for the sentinel products , is welcomed from all parties, given welcomed from all parties, given conditions and provisions presented conditions and provisions presented in following slides.in following slides.

Submitting additional information Submitting additional information for use in ComET™for use in ComET™

1.1. Information is to be submitted to the Information is to be submitted to the model architects—The LifeLine Group—model architects—The LifeLine Group—for application to the model.for application to the model.

www.TheLifeLineGroup.orgwww.TheLifeLineGroup.orgThe LifeLine GroupThe LifeLine Group

4610 Quarter Charge Drive4610 Quarter Charge Drive

Annandale, VA 22003Annandale, VA 22003Data submission will be noted as to date of receipt and will be Data submission will be noted as to date of receipt and will be

considered by LLG scientists for inclusion in the model. If data considered by LLG scientists for inclusion in the model. If data are used in the model, reference to the submitter and source are used in the model, reference to the submitter and source will be made in the ComET™ Documentation materials.will be made in the ComET™ Documentation materials.

NO INFORMATION WILL BE CONSIDERED CONFIDENTIALNO INFORMATION WILL BE CONSIDERED CONFIDENTIAL

Submitting additional public Submitting additional public informationinformation

for use in ComET™ for use in ComET™

2.2. No information will be considered No information will be considered confidential or proprietaryconfidential or proprietary

If information is used, the source will be If information is used, the source will be identified in the ComET™ documentation. identified in the ComET™ documentation. LLG will maintain files of all submitted LLG will maintain files of all submitted information and will use the submissions information and will use the submissions at their discretion for implementation in at their discretion for implementation in ComET™.ComET™.

All submissions will be available to HC.All submissions will be available to HC.

Submitting additional public Submitting additional public information for use in ComET™information for use in ComET™

3.3. Information Information must be relevant to overall must be relevant to overall type of product—NOT BRAND SPECIFICtype of product—NOT BRAND SPECIFIC

Remember: Remember:

Information must apply to the highest Information must apply to the highest plausible exposure scenario from that plausible exposure scenario from that

product type. product type.

Submission of Confidential Submission of Confidential Information for ComET™Information for ComET™

Confidential information may be Confidential information may be submitted directly to Health submitted directly to Health

Canada, as described in HC handout Canada, as described in HC handout

Such information may be used for Such information may be used for comparison exercisescomparison exercises

Valuable information for Valuable information for ComET™ComET™

Substance occurrence in productsSubstance occurrence in products Substance contribution to overall Substance contribution to overall

product ingredientsproduct ingredients Underlying algorithms and values for Underlying algorithms and values for

substances in those algorithmssubstances in those algorithms Environmental source exposure Environmental source exposure

information information

Portraying highest plausible Portraying highest plausible exposure elements for a exposure elements for a typetype of of

productproduct

Example: personal care product Example: personal care product

Multiple brands of same type of product: each with different concentration of substance ranging from 0.5 %to 15%

Brand with 15% concentration of subject substance selected for sentinel product values

15%

10%

7% 15%

Submitting additional information for Submitting additional information for use in ComET™: critical informationuse in ComET™: critical information

4.4. Information Information can address: can address: Generic information about product uses and Generic information about product uses and

activity patterns that define exposure activity patterns that define exposure parameters.parameters.

Were the right sentinel products selected for Were the right sentinel products selected for the substance? the substance?

Were the right algorithms applied to the Were the right algorithms applied to the sentinel product?sentinel product?

Were the right values applied to the algorithms Were the right values applied to the algorithms – for the product types, not specific brands of – for the product types, not specific brands of products.products.

Process and Policies for Consideration and Process and Policies for Consideration and Application of Submitted InformationApplication of Submitted Information

Data must not be confidential—will be available for Data must not be confidential—will be available for viewing via ComET™viewing via ComET™

Must be submitted in writing with full citation. If Must be submitted in writing with full citation. If experimental data, full description of protocol, experimental data, full description of protocol, data, conclusions.data, conclusions.

Must apply to all specific products within the Must apply to all specific products within the sentinel product groupsentinel product group

Information must be of better “pedigree” than Information must be of better “pedigree” than initial information initial information

Information must adhere to philosophy of Information must adhere to philosophy of transparencytransparency

Information must bring a degree of refinement to Information must bring a degree of refinement to ComET™ComET™