Qualitative Approach to Comparative Exposure in

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

2

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

PROBLEM FORMULATION GENERIC CONCEPTUAL MAP – HUMANS

Greggs W, et al. (2018) IEAM. 9

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

jentanir@towardsafer.com www.towardsafer.com

(202) 258-7951

Michelle Embry HESI

membry@hesiglobal.org www.hesiglobal.org

(202) 659-3306