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

4

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]

7

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

18

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]

19

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