qualitative approach to comparative exposure in
TRANSCRIPT
Qualitative Approach to Comparative
Exposure in Alternatives Assessment
Jennifer Y. Tanir (Toward Safer LLC)
on behalf of HESI Sustainable Chemical Alternatives Committee
November 1, 2018
• Presentation Co-Authors: – William Greggs (Soleil Consulting) – Thomas Burns (Novozymes) – Michelle Embry (Health and Environmental Sciences Institute) – Peter Fantke (Technical University of Denmark) – Bonnie Gaborek (Specialty Products Division of DowDuPont) – Lauren Heine (Northwest Green Chemistry) – Olivier Jolliet (University of Michigan) – Derek Muir (Environment and Climate Change Canada) – Neha Sunger (West Chester University) – Margaret Whittaker (ToxServices)
• Additional Participants in the HESI Sustainable Alternatives Committee
• Health and Environmental Sciences Institute (HESI)
ACKNOWLEDGEMENTS
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Creating science-based solutions for a sustainable, healthier world.
HEALTH AND ENVIRONMENTAL SCIENCES INSTITUTE (HESI)
www.hesiglobal.org 3
Academic & Basic
Research Sector
Industry R&D Foundations
& NGOs
Govt Research & Regulation
SAFETY & INNOVATION FOR HUMAN &
ENVIRONMENTAL HEALTH
HESI SUSTAINABLE CHEMICAL ALTERNATIVES COMMITTEE’S PROJECTS
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Exposure
• Developing a qualitative, comparative exposure assessment methodology.
Data Gaps
• Developing a best practices guide for filling human health and environmental safety data gaps at each stage of product development.
Decision Analysis
• Surveying companies to study how chemical ingredient and product substitution decisions are made.
EXCERPT FROM NAS AA FRAMEWORK
National Research Council. 2014. A framework to guide selection of chemical alternatives. Washington (DC): Natl Academies. 5
HESIQualita,veExposureNAS AA
FRAMEWORK REPORT:
COMPARATIVE
EXPOSURE PATHS
ModeledExposure
National Research Council. 2014. A framework to guide selection of chemical alternatives. Washington (DC): Natl Academies. 6
QUALITATIVE-COMPARATIVE EXPOSURE PROCESS
5) Overall Qualitative Exposure Assessment
4) Consider Relevance-Confidence-Data Gaps
3) Compare Exposure Potential of Alternatives
2) Determine Exposure Parameter Information
1) Problem Formulation – Conceptual Exposure Map
Greggs W, et al. (2018) Qualitative approach to comparative exposure in alternatives assessment. Integr Environ Assess Manage. DOI:10.1002/ieam.4070 [OPEN ACCESS]
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PROBLEM FORMULATION GENERIC CONCEPTUAL MAP
Life Cycle Stage
Action to Use Product
Expected Receiving Medium
Release Mechanism & Fate and Transport During/After Use
Potential Exposure Medium
Exposure Routes
Populations/Receptors
Greggs W, et al. (2018) IEAM. 8
EXPOSURE COMPARISON PARAMETERS PRODUCTEXPOSUREPARAMETERS
Ingredientfunc,oninproductLifecyclestageExposedpopula,onsProductformProductdeliverytype
Expectedexposurerouteand/orusepa?ern
Frequency,dura,on,andamountofuseIngredientconcentra,oninproductIngredienttotalusevolume
Otheringredientsinformulathatmaydifferen,allyimpactpoten,alfor&typeofexposure
Accessibilityofingredientinproductandduringuse
Separa,onpoten,alduringproductlife
ProductdisposalmethodProductdisposalmethod
INGREDIENTEXPOSUREPARAMETERSSMILESandstructureVaporpressureSolubilityinwaterMolecularweightPar,clea?ribute(size)Ambientphysicalstatemel*ngpointorboilingpointBioavailabilityPredictedskinpermeability(logKp)%Humanoralabsorp*onOctanol-waterpar,,oncoefficient(LogKow)Octanol-airpar,,oncoefficient(LogKoa)Soilsorp,onpar,,oncoefficient(logKoc)Henry'slawconstantBioaccumula,on(BAF/BCF)PersistenceWater,soil,sediment,orairhalf-lifeDegradabilityEnvironmentalFateWater,soil,sediment,orairSewagetreatmentplantremoval
We defined a classification scheme for most parameters to compare the magnitude of differences to exposure potential.
Greggs W, et al. (2018) IEAM. 10
IngredientInforma,on TargetIngredient
Poten,alReplacement
ExposureImpact(+1/0/-1)
Ra,onale-Comment Relevance Confidence
Vaporpressure
Solubility
Molecularweight
Par,clea?ributes-size
AmbientphysicalstateMel*ngPoint-BoilingPoint
Bioavailability
Predictedskinpermeability
%Humanoralabsorp*on
Par,,oning
Octanol-water(LogKow) Octanol-air(LogKoa) Soilsorp*on(logKoc)
Henry’sLawConstant
Bioaccumula,on
Persistence
Water,soil,sediment,airhalf-life
Degradability
EnvironmentalFate
Water,soil,sediment,orair
Sewagetreatmentplantremoval
PARAMETER DATA AND COMPARISON
Greggs W, et al. (2018) IEAM. 11
RELEVANCE – CONFIDENCE – DATA GAPS
High – Medium – Low Definitions for each
Data Gaps • The relative
importance of any missing information
Confidence • The degree to
which there is an assurance in the data being compared
Relevance • The extent to
which a parameter is associated with the exposure to the ingredient through its use in a specific product application
Greggs W, et al. (2018) IEAM. 12
QUALITATIVE-COMPARATIVE EXPOSURE PROCESS
5) Overall Qualitative Exposure Assessment
4) Consider Relevance-Confidence-Data Gaps
3) Compare Exposure Potential of Alternatives
2) Determine Exposure Parameter Information
1) Problem Formulation – Conceptual Exposure Map
Greggs W, et al. (2018) IEAM. 13
CASE STUDIES
• Two case studies were selected to illustrate the application of the methodology: – replacement of musk xylene with Muscone in eau de
toilette – replacement of di(2-ethylhexyl) phthalate with di(2-
ethylhexyl) terephthalate in toys
Greggs W, et al. (2018) IEAM. 14
CASE STUDY DOCUMENTATION Eau de toilette 0.4% max *
Target Ingredient Ref Potential Replacement Ref Exposure Impact (+1/0/-1)
Rationale-Comment
Relevance Confidence
Ingredient Musk xylene (CASRN 81-15-2)
3-methyl-cyclopentadecanone (Muscone) 541-91-3
N/A N/A N/A N/A
SMILES Cc1c(c(c(c(c1N(=O)(=O))C(C)(C)C)N(=O)(=O))C)N(=O)(=O)
CC1CCCCCCCCCCCCC(=O)C1
N/A N/A N/A N/A
Structure N/A N/A N/A N/A
INGREDIENT EXPOSURE PARAMETERS
Vapor pressure
6.35E-07 mm Hg @ 25°C Vapor-particulate phase
USEPA (2012)
0.000469 mm Hg @ 25°C Mostly vapor phase
USEPA (2012)
-1 (derm) +1 (inh)
-1 for dermal because evaporates faster; + 1 for inh because more volatile
High because parameter indicates in this circumstance the dominant exposure route for each compound
Medium because both estimated data
CH3
NO
OH3C
H3CCH3
N
O
O
H3C N OO
CH3
CH2
CH2O
Greggs W, et al. (2018) IEAM. 15
CASE STUDY OUTCOMES Eau de Toilette (Musk xylene – Muscone) • Exposure to the alternative is likely to be lower or the same
- Exposure to the environment clearly reduced - However, the Musk xylene dermal exposure pathway shifts to
inhalation for Muscone, based on physical properties • Key Uncertainties / Data Needs:
- Maximum concentration of the alternative (Muscone) - Exposure shift – need quantitative estimates to:
o Compare exposure estimates to relevant hazard levels o Determine if Muscone provides a human safety improvement
Greggs W, et al. (2018) IEAM. 16
CASE STUDY OUTCOMES Toys (DEHP – DEHT) • Exposure to the alternative is likely to be the same or possibly
slightly lower - Lower water solubility and lower skin permeability - However, higher log Kow suggests easier absorption and
longer half-life in the body • Key Uncertainties / Data Needs:
- Rate of migration to the toy surface for each substance. This would allow better assessment of transfer into the child’s saliva during mouthing and onto child’s skin during contact.
- Quantitative assessment would address uncertainties in the magnitude of competing high-relevance parameters above.
Greggs W, et al. (2018) IEAM. 17
Benefits of Comparative-Qualitative Approach • Concept easy to understand, interpret, communicate • Considers all key components of potential exposure • Stepwise protocol/procedure • Useful way to structure expert knowledge • Basis for judging same/lower exposure vs. higher or different
route and needing quantitative assessment • Can improve AA decisions
BENEFITS AND LIMITATIONS OF STUDY
Greggs W, et al. (2018) IEAM.
Challenges/Limitations • Requires exposure expertise • Availability/data gaps for key information • Did not test a case study with product design changes • Difficult to pinpoint most important exposures and their
magnitude without quantitative assessment
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THANK YOU!
CONTACT INFORMATION:
Reference: Greggs W, et al. (2018) Qualitative approach to comparative exposure in alternatives assessment. Integr Environ Assess Manage. DOI: 10.1002/ieam.4070 [OPEN ACCESS]
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Jennifer Y. Tanir Toward Safer LLC
[email protected] www.towardsafer.com
(202) 258-7951
Michelle Embry HESI
[email protected] www.hesiglobal.org
(202) 659-3306