Approaches for Rapid Exposure-Based Prioritization of ...
Approaches for Rapid Exposure-Based Prioritization of ...
Approaches for Rapid Exposure-Based Prioritization of ...
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<strong>Approaches</strong> <strong>for</strong> <strong>Rapid</strong> <strong>Exposure</strong>-<strong>Based</strong><br />
<strong>Prioritization</strong> <strong>of</strong> Environmental Chemicals<br />
Jade Mitchell-Blackwood, Peter Egeghy and Daniel Vallero<br />
SRA <strong>Exposure</strong> Assessment Specialty Group Tele-Seminar<br />
June 8, 2011<br />
Although this work was reviewed by EPA and approved <strong>for</strong> publication, it may<br />
not necessarily reflect <strong>of</strong>ficial Agency policy.<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Draft – do not cite or quote<br />
06-08-11
2<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Goal<br />
Generalized parsimonious screening models <strong>for</strong><br />
predicting chemical exposures<br />
– Innovative, rapid and effective<br />
– Prioritize chemicals <strong>for</strong> further safety testing<br />
– Combine in<strong>for</strong>mation with ToxCast<br />
Draft – do not cite or quote
Chemical Safety <strong>for</strong> Sustainability Research<br />
3<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Draft – do not cite or quote<br />
http://www.epa.gov/ord/priorities/chemicalsafety.htm
<strong>Exposure</strong><br />
Scenario<br />
Development<br />
4<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
PRODUCT n<br />
PRODUCT …<br />
Chemical<br />
Manufacture<br />
Chemical<br />
Transportation<br />
Production/<br />
Formulation<br />
PRODUCT PRODUCT 4 5<br />
PRODUCT 3 PRODUCT 6<br />
PRODUCT 7<br />
PRODUCT 2<br />
PRODUCT 8<br />
PRODUCT 1<br />
Product<br />
Use<br />
Product<br />
Disposal<br />
Workplace<br />
<strong>Exposure</strong><br />
Environmental<br />
Release<br />
Environmental<br />
Disposal<br />
Market Share<br />
Population<br />
Location<br />
Frequency<br />
Timing<br />
RELEASE FATE / TRANSPORT CONCENTRATION ACTIVITY EXPOSURE<br />
Release<br />
Transport<br />
Reaction<br />
Environmental<br />
Release<br />
Food<br />
Air<br />
Indoor<br />
Air<br />
Outdoor<br />
Air<br />
Surface<br />
Dust<br />
Water<br />
Water<br />
Land<br />
Incineration<br />
Recycling Sewage<br />
Recycling<br />
Treatment<br />
Sewage<br />
Recycling<br />
Treatment<br />
Sewage<br />
Treatment<br />
Water<br />
Air<br />
Land<br />
Soil<br />
Draft – do not cite or quote<br />
Food<br />
A A A C C C T T T I I I V V V I I I T T T I I I E E E SS<br />
S<br />
Food<br />
A A A C C C T T T I I I V V V I I I T T T I I I E E E SS<br />
S<br />
A A A C C C T T T I I I V V V I I I T T T I I I E E E SS<br />
S<br />
Human Human Human<br />
<strong>Exposure</strong><br />
<strong>Exposure</strong><br />
<strong>Exposure</strong><br />
Human Human Human<br />
<strong>Exposure</strong><br />
<strong>Exposure</strong><br />
<strong>Exposure</strong><br />
Human Human Human<br />
<strong>Exposure</strong><br />
<strong>Exposure</strong><br />
<strong>Exposure</strong>
5<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Draft – do not cite or quote
1. Leverage knowledge from existing prioritization tools<br />
2. Per<strong>for</strong>m a gap analysis<br />
3. Identify the type, quantity and quality <strong>of</strong> in<strong>for</strong>mation<br />
needed <strong>for</strong> a new approach<br />
6<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Draft – do not cite or quote<br />
<strong>Exposure</strong>-<strong>Based</strong> <strong>Prioritization</strong><br />
Challenge Objectives<br />
ExpoCast<br />
April 6-7, 2010<br />
http://epa.gov/ncct/expocast/
Inputs<br />
Product characteristics<br />
Chemical properties<br />
Functional categories <strong>for</strong><br />
chemicals<br />
Industrial process categories<br />
Consumer product use<br />
categories and selection <strong>of</strong><br />
sentinel products<br />
Emission characteristics<br />
7<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
<strong>Exposure</strong>-<strong>Based</strong> <strong>Prioritization</strong><br />
Challenge Requirements<br />
Draft – do not cite or quote<br />
Assumptions<br />
<strong>Exposure</strong> scenarios<br />
<strong>Exposure</strong> pathways<br />
Defaults (exposure factors,<br />
etc.)<br />
Units <strong>of</strong> prioritization metric<br />
and other model outputs<br />
Explicit use <strong>of</strong><br />
pr<strong>of</strong>essional/expert<br />
judgment<br />
http://epa.gov/ncct/expocast/
<strong>Exposure</strong>-based<br />
<strong>Prioritization</strong><br />
Challenge<br />
Models<br />
52 chemicals to<br />
rank based on<br />
exposure<br />
8<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
MENTOR -<br />
PROTEGE<br />
RAIDAR<br />
and<br />
FHX<br />
GExFRAME<br />
EXPOSURE<br />
INFORMATION<br />
EFAST<br />
Draft – do not cite or quote<br />
USEtox<br />
SHEDS
Risk Assessment IDentification Ranking(RAIDAR) and<br />
Far-field Human <strong>Exposure</strong> (FHX)<br />
Diffuse source<br />
Regional scale<br />
Mechanistic mass balance model<br />
Integrates fate-and-transport in the environment and<br />
bioaccumulation in representative species and humans<br />
Source: Jon Arnot, Ph.D.<br />
ARC Arnot Research & Consulting Inc.<br />
9<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Far-field Models<br />
Draft – do not cite or quote
UNEP-SETAC Toxicity Model (USEtoxTM)<br />
• Seven (7) compartments <strong>of</strong> emission at continental scale<br />
embedded in global scale<br />
• Two (2) routes <strong>of</strong> exposure: Inhalation via continental,<br />
urban and recently indoor air; Ingestion via drinking water,<br />
fish, exposed agriculture products, root crops, meat and<br />
10<br />
dairy product<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Far-field Models<br />
Overall<br />
US impact<br />
In case/year<br />
TRI – Toxic<br />
Release inventory<br />
US Total<br />
assessment<br />
Ground-, fresh- or<br />
marine water<br />
Algae<br />
Crustacae<br />
Fish<br />
Oral<br />
exposure<br />
Gastrointestinal tract<br />
NEI – National<br />
Emission inventory<br />
Agricultural<br />
or natural soil<br />
Vegetation crop<br />
Animal meat<br />
Blood<br />
Outdoor<br />
air<br />
Other target organs<br />
Damage on human health<br />
Chemical<br />
manufacture<br />
Inhalation<br />
exposure<br />
Lung, nose<br />
Chemical<br />
transportation<br />
production disposal<br />
Product disposal<br />
Product life cycle<br />
workplace<br />
Home<br />
indoor<br />
air & dust<br />
Skin<br />
Fate<br />
Dermal<br />
exposure<br />
Internal exposure<br />
Dose - response<br />
& severity<br />
Production/<br />
Formulation<br />
Product<br />
use<br />
Intake<br />
fraction<br />
1<br />
Draft – do not cite or quote<br />
Impact per<br />
kg chemical<br />
or product<br />
function<br />
Per kg<br />
Emission<br />
characterization<br />
Source: Oliver Jolliet, University <strong>of</strong> Michigan
11<br />
GExFRAME/Scibin and<br />
Cumulative and Aggregate Risk Evaluation<br />
System (CARES)<br />
• Population (US Census)<br />
• Dietary (Food & Drinking Water)<br />
• Residential Product Use<br />
• Near field or far field environments <strong>of</strong> the general population<br />
• Several exposure scenarios:<br />
– Workers during manufacturing<br />
– Product applications<br />
– Post application<br />
– Dietary<br />
– Drinking water<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Near-field Models<br />
Draft – do not cite or quote<br />
Source: Muhilan Pandian, Infoscientific
12<br />
<strong>Exposure</strong> and Fate Assessment Screening<br />
Tool (EFAST)<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Near-field Models<br />
• Screening-level estimates <strong>of</strong> the concentrations <strong>of</strong><br />
chemicals<br />
–Released to air<br />
–Surface water<br />
–Landfills<br />
–Consumer products<br />
• Potential inhalation, dermal and ingestion dose rates<br />
• Designed to reasonably overestimate exposures<br />
Draft – do not cite or quote<br />
http://www.epa.gov/opptintr/exposure/pubs/efast.htm
<strong>Prioritization</strong>/Ranking <strong>of</strong> Toxic <strong>Exposure</strong>s with<br />
GIS Extension (PRoTEGE)<br />
•Individual, Community and<br />
Population exposures<br />
•Four life-cycle stages<br />
•Ingestion and inhalation in<br />
occupational, ambient and<br />
personal environments<br />
(residential, transportation &<br />
public)<br />
13<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Draft – do not cite or quote<br />
Far-field and Near-field Sources<br />
Source: Panos G. Georgopoulos, Sastry S. Isukapalli, and Paul J. Lioy, Environmental and<br />
Occupational Health Sciences Institute (EOHSI)
14<br />
Stochastic Human <strong>Exposure</strong> and Dose<br />
Simulation (SHEDS)<br />
1. SHEDS-Dietary<br />
(part <strong>of</strong> SHEDS-<br />
Multimedia)<br />
2. SHEDS-Residential<br />
(part <strong>of</strong> SHEDS-<br />
Multimedia)<br />
3. SHEDS-Air Toxics<br />
and APEX<br />
4. SHEDS-Soil/dust<br />
5. SHEDS-PM<br />
http://www.epa.gov/heasd/products/sheds_multimedia/sheds_mm.html<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Draft – do not cite or quote<br />
Far-field and Near-field Sources
15<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Draft – do not cite or quote<br />
<strong>Exposure</strong> Science Framework
16<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Analysis <strong>of</strong> Challenge Results<br />
Key Questions:<br />
1. How well do the model rankings correlate with each other?<br />
2. What factors are influencing the rankings (i.e. chemical properties,<br />
emissions data, etc.)?<br />
3. What domains <strong>of</strong> in<strong>for</strong>mation lead to model differences which lead<br />
to different results?<br />
Methods:<br />
• Rank to Rank Correlation<br />
• Binning or categorizing<br />
• Chemoin<strong>for</strong>matic visualization across parameter space<br />
• Analysis <strong>of</strong> Variance (ANOVA)<br />
• Crowdsourcing<br />
Draft – do not cite or quote
17<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
<strong>Exposure</strong> Metrics <strong>for</strong> <strong>Prioritization</strong><br />
RAIDAR and FHX<br />
• Intake fraction (unitless)<br />
• Intake rate (mg/d or kg/h)<br />
• Concentration in humans (mg/kg)<br />
USEtox<br />
• Intake Fraction (kg intake/kg emitted)<br />
GExFRAME<br />
• Categories and classifications <strong>of</strong> potential exposure<br />
• Inhalation, Dermal and/or Oral (mg/kg/day)<br />
PRoTEGE<br />
• Tier 1: Pervasiveness, Persistence, Severity and Efficacy<br />
•Tier 2: �mol/day by route (10th, 50th and 90th percentiles)<br />
SHEDS<br />
• Categories <strong>of</strong> potential exposure by pathway and use based on similar<br />
properties<br />
• Absorbed dose by route (mg/kg/day)<br />
EFAST<br />
• Predicted Lifetime Average Daily Dose (LADD) in mg/kg/day<br />
Draft – do not cite or quote
18<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Challenge Results: Far-field<br />
Draft – do not cite or quote<br />
•Differentiation across several orders <strong>of</strong> magnitude<br />
•Broad assumptions
19<br />
Chemical Description<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Challenge Results: Near-field<br />
1 Previously used and currently not<br />
found in human exposure media<br />
2 Previously used and currently<br />
found in human exposure media<br />
3 Present in human exposure media<br />
during industrial use<br />
4 Found in food and/or drinking water<br />
5 Found in consumer use products<br />
6 A pesticide currently in use<br />
•Semi-quantitative approaches<br />
•Tiered exposure metrics based on in<strong>for</strong>mation availability<br />
Draft – do not cite or quote
20<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Points <strong>of</strong> Interest<br />
Draft – do not cite or quote<br />
1. Chemicals as single substances rather than embedded in<br />
products.<br />
2. Amount <strong>of</strong> the chemical used vs. the amount produced<br />
3. Integration <strong>of</strong> far-field and near field source models is also an<br />
important challenge<br />
4. Extension <strong>of</strong> exposure characterization beyond occurrence,<br />
persistence and bioaccumulation<br />
5. Potential lifetime <strong>of</strong> the person and the products is required.<br />
6. Specific in<strong>for</strong>mation about the target user – age and genetic<br />
susceptibility<br />
7. Proper categorization: Function? Types? Number <strong>of</strong><br />
microenvironments?<br />
8. ADME and internal dose
21<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
Future Work<br />
•Uncertainty and sensitivity analysis<br />
•Second ExpoCast Workshop – August 2011<br />
•Application <strong>of</strong> a multi-criteria decision framework<br />
Physical<br />
Chemical<br />
Properties<br />
Draft – do not cite or quote<br />
Sociology<br />
Psychology<br />
Economics
22<br />
Office <strong>of</strong> Research and Development<br />
National <strong>Exposure</strong> Research Laboratory<br />
For more in<strong>for</strong>mation:<br />
Jade Mitchell-Blackwood<br />
mitchell-blackwood.jade@epa.gov
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