Concept and Construction of the “Sentinel Product Functions” “Sentinel Product Functions” Criteria and Information Sources Dr. Christine Chaisson The LifeLine Group Slides and Materials Copyright Protected

Sentinel Product Functions (SPF): The Heart of ComET™ ComET™ is designed to highlight the highest plausible exposure scenarios that could be presented to subgroups of the population as a consequence of the use of a substance in a consumer product. And… The highest plausible exposure profile for the substance is defined as the sum of the exposures presented by all SPF’s for that substance. [via all routes or specific routes]

Sentinel Product Functions (SPF): The Heart of ComET™ The highest plausible exposure profile for the substance is defined as the sum of the exposures presented by all SPF’s for that substance. [via all routes or specific routes] This will be defined by the scenario of USE of that type of product… AND USE will be variable across subpopulations

ComET™ vs. Full Exposure Assessment Models ComET™ Full Exposure Assessment Models operates with minimum of data on specific chemicals operates with minimum of data on specific chemicals Displays highest plausible exposure scenarios from array of products possible from the substance Displays highest plausible exposure scenarios from array of products possible from the substance Addresses TYPES of products with common use scenarios—NOT specific brands Addresses TYPES of products with common use scenarios—NOT specific brands May overstate exposure, but in priority setting justifies setting substances aside from further consideration or additional assessment May overstate exposure, but in priority setting justifies setting substances aside from further consideration or additional assessment requires more data-rich situations for each chemical requires more data-rich situations for each chemical Displays representative exposure for all or some product-specific scenarios Displays representative exposure for all or some product-specific scenarios Addresses specific product brands with brand-specific information Addresses specific product brands with brand-specific information Intent to display exact exposure at a given point (average, 95 th percentile, etc) or a full distribution of the exposures across the subject population Intent to display exact exposure at a given point (average, 95 th percentile, etc) or a full distribution of the exposures across the subject population

Portraying highest plausible exposure elements for a type of 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) 1 Definition of “Sentinel Product” Definition of “Sentinel Product” –Not the “representative product” –A type of product—not brand of product –Illustrates the general category of product in terms of manufacturing, design and use Elements of Concern Elements of Concern –Subpopulations: differences in terms of route of exposure, duration of exposure, magnitude of exposure

Subpopulations to be Considered USE of a type of product will vary across sub-populations Factors relevant to exposure will vary across sub-populations 0-<0.5 years <5 years 5 - <12 years 12-<20 years years 60+ years Food Intake Inhalation Rates Surface Areas whole body hands, legs, feet, etc. Water intake Soil ingestion, adherence Body Weight

Example: Population Differences Consider USE profile in terms of frequency, duration, magnitude Consider routes of exposure, etc. 0-<0.5 years <5 years 5 - <12 years 12-<20 years 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) 2 Multiple sentinel products may be chosen for a given chemical Multiple sentinel products may be chosen for a given chemical –Age groups –Duration/frequency/periodicity of exposure –Magnitude of exposure See ComET™ Documentation: Sentinel Product 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 Gathering Objectives: –Stock ComET™ with information about types of products sufficiently representative for Existing Chemicals (the DSL) –To extent possible, make the information and the algorithms that apply the information TRANSPARENT  Confidence of the public and stakeholders  Scrutiny improves performance  Invites submission of better information –Regarding choice of sentinel products –Regarding algorithms used –Regarding values applied to algorithms –Submission of information leading to refined scenarios leading to lower priority for further work

Options for Information Gathering Publicly available data: Aids transparency of/public confidence in ComET™ Aids transparency of/public confidence in ComET™ Necessary information available? Necessary information available? New and better sources of information becoming available over time New and better sources of information becoming available over time Industry-submitted confidential information: Useful for QA checks on ComET™ Useful for QA checks on ComET™ Not transparent, not helpful to attract better information or for building public confidence. Not transparent, not helpful to attract better information or for building public confidence.

Using Publicly Available Information Sources: Efficacy and Adequacy Existing Process Checked for Efficacy and Adequacy: Information Content Exercise Public Information sought by “naïve” researcher” Public Information sought by “naïve” researcher” Development of search strategies and collection of key web sites as process evolved. Development of search strategies and collection of key web sites as process evolved. Results compared to information already available to HC staff “experienced” researcher—including CBI submitted by industry. (comparison made by HC scientists) Results compared to information already available to HC staff “experienced” researcher—including CBI submitted by industry. (comparison made by HC scientists)

Overview of Findings from Study Favorable results…. public sources are adequate and available Search Strategy Guide is an important document Search Strategy Guide is an important document –Accrual of valuable web sites and guidance for using the sites –Use of CAS, common names, product category names, etc. –New and better sources becoming available, for example  ExpoFacts– European Exposure Factors Sourcebook – Some substances present unique challenges Some substances present unique challenges –Ubiquitous substances with many, many uses (copper) –Monomers, components of polymers (residue concentrations in final products) –Physical/Chemical Properties of UVCB’s

Transparency in Application of Publicly Available Data Data sources and compendium of data recovered for each chemical can be filed and updated electronically. Data sources and compendium of data recovered for each chemical can be filed and updated electronically. Summary sheets for each chemical includes metrics extracted for application to model’s algorithms Summary sheets for each chemical includes metrics extracted for application to model’s algorithms Transparency of all this useful for all stakeholders to identify: Transparency of all this useful for all stakeholders to identify: –Choice of impossible sentinel product –Missing sentinel product –Assignment of metrics not possible for sentinel product –Scenarios where sum of exposures from non-sentinel products could possibly be greater than exposures from sum of sentinel products. Is this more probable where the chemical has many uses? –Level of uncertainty in the exposure estimates. Qualitative notation is made for each metric where defaults and overestimation was applied because of paucity of information

Assuring Adequacy of Use of Publicly Available Information Sources for ComET™ Going forward—improving the process, sharing experience with users –Upgrading the Search Strategy Documents –Incorporating New Information Submitted to LLG/HC- EC for use in ComET™ –Continued upgrading of all documentation consistent with additions to ComET™  Sentinel Product Functions Taxonomy  Master DSL Scenario List  SPF Algorithm Scenarios

Assuring Adequacy of Use of Publicly Available Information Sources for ComET™ Going forward---assuring all chemical use categories can be identified 1. Formal screen to assure all known uses of existing DSL substances are represented by full library of Sentinel Product Functions. This study and its results should be documented as a quality control report. 1. ComET™ and its documentation will be periodically reviewed for quality. Operational experience will be considered.

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

Submitting additional information for use in ComET™ 1. Information is to be submitted to the model architects—The LifeLine Group—for application to the model. The LifeLine Group 4610 Quarter Charge Drive Annandale, VA Data submission will be noted as to date of receipt and will be considered by LLG scientists for inclusion in the model. If data are used in the model, reference to the submitter and source will be made in the ComET™ Documentation materials. NO INFORMATION WILL BE CONSIDERED CONFIDENTIAL

Submitting additional public information for use in ComET™ 2. No information will be considered confidential or proprietary If information is used, the source will be identified in the ComET™ documentation. LLG will maintain files of all submitted information and will use the submissions at their discretion for implementation in ComET™. All submissions will be available to HC.

Submitting additional public information for use in ComET™ 3. Information must be relevant to overall type of product—NOT BRAND SPECIFIC Remember: Information must apply to the highest plausible exposure scenario from that product type.

Submission of Confidential Information for ComET™ Confidential information may be submitted directly to Health Canada, as described in HC handout Such information may be used for comparison exercises

Valuable information for ComET™ Substance occurrence in products Substance occurrence in products Substance contribution to overall product ingredients Substance contribution to overall product ingredients Underlying algorithms and values for substances in those algorithms Underlying algorithms and values for substances in those algorithms Environmental source exposure information Environmental source exposure information

Portraying highest plausible exposure elements for a type of 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 use in ComET™: critical information 4. Information can address: Generic information about product uses and activity patterns that define exposure parameters. Generic information about product uses and activity patterns that define exposure parameters. Were the right sentinel products selected for the substance? Were the right sentinel products selected for the substance? Were the right algorithms applied to the sentinel product? Were the right algorithms applied to the sentinel product? Were the right values applied to the algorithms – for the product types, not specific brands of products. Were the right values applied to the algorithms – for the product types, not specific brands of products.

Process and Policies for Consideration and Application of Submitted Information Data must not be confidential—will be available for viewing via ComET™ Data must not be confidential—will be available for viewing via ComET™ Must be submitted in writing with full citation. If experimental data, full description of protocol, data, conclusions. Must be submitted in writing with full citation. If experimental data, full description of protocol, data, conclusions. Must apply to all specific products within the sentinel product group Must apply to all specific products within the sentinel product group Information must be of better “pedigree” than initial information Information must be of better “pedigree” than initial information Information must adhere to philosophy of transparency Information must adhere to philosophy of transparency Information must bring a degree of refinement to ComET™ Information must bring a degree of refinement to ComET™