Overview of Risk Assessment 

Under TSCA -

Tala Henry Ph.D.

Director

Risk Assessment Division 

Office of Pollution Prevention & Toxics 

1
OUTLINE

• Introduction: Assessment Paradigm under 

TSCA

• TSCA Work Plan Chemicals Assessments

• OPPT’s Risk Assessment Process

• More Information TSCA Work Plan Chemicals

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Risk Assessment Paradigm 

under TSCA

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RISK ASSESSMENT PARADIGM UNDER TSCA

Under TSCA, OPPT evaluates and regulates, as 

appropriate, the full life cycle, i.e., manufacture 

(import), distribution in commerce, use and 

disposal, of industrial chemicals

− Safety Evaluation for a Wide Array of Industrial 

Chemicals:

− Existing and New Industrial Chemicals

− Data Availability/Quality Varies, but generally 

limited/incomplete

− New Risk Assessment/Management Challenges 

Continually Arise as New Chemistries and New 

Uses Emerge

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Food Additives, 

Drugs & Cosmetics

~2,000 AI

Federal Food, Drug, and 

Cosmetic Act 

By OPP & FDA

FFDCA requires 

experimental data

Industrial 

Chemicals

~84,000 Chemicals

Regulated under Toxic 

Substances Control Act 

(TSCA)

By Office of Pollution, 

Prevention, and Toxics 

(OPPT) 

 New Chemical 

Submissions do not 

require “new” data

 NO mandate to assess 

existing chemicals

Assessment Paradigm: How is TSCA Different?

U.S. Chemical Universe

Pesticides

~2000 Chemicals (Active 

Ingredients)

Reviewed and Regulated 

under FIFRA By Office of 

Pesticides (OPP)

FIFRA requires 

experimental data
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DATA FOR ASSESSMENT UNDER TSCA

• New Chemicals

− Computational approaches used extensively

• QSAR and Expert Systems

• Read-Across from Analogs/Categories

− Tiered-Testing Approach: requests for higher tiered 

testing contingent on screening results

• Existing Chemicals

− Established Test Guidelines; most testing for 

toxicity is in vivo

− Read-Across from Analogs/Categories used 

extensively in screening programs (e.g., HPV) 

− Categories/Clusters used some in TSCA Work Plan 

Assessments

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Existing Chemicals 

Assessment under TSCA:

TSCA Work Plan

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TSCA WORK PLAN

• Criteria for Selecting Chemicals for Assessment

− Hazard

• Potentially of concern to children’s health (reproductive or 

developmental effects)

• Neurotoxic effects

• Probable or known carcinogens

• Aquatic toxicity 

− Exposure

• Used in products to which children might be exposed

• Detected in biomonitoring 

• Data reported to Toxic Release Inventory & under Chemical 

Data Reporting Rule 

− Persistence & Bioaccumulation

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TSCA WORK PLAN

Sum of 

Hazard, 

Exposure and 

P/B scores

7 to 9: High 

(Work Plan)

4 to 6: 

Moderate 1 to 3: Low

• Work Plan 

published with 

methodology in 

2012 

• Work Plan scores 

updated in 2014

• Of the 345 

chemicals, 90 

currently scored 

high and are 

considered Work 

Plan chemicals 

https://www.epa.gov/assessing-and-managing-chemicals-undertsca/tsca-work-plan-chemicals

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TSCA WORK PLAN: ASSESSMENTS

Assessing Chemicals for Safety

Work Plan

Chemicals

Risk Action

(Voluntary, Regulatory)

No Risk No Action

https://www.epa.gov/assessing-and-managing-chemicals-undertsca/tsca-work-plan-chemicals

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https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/assessments-tsca-work-plan-chemicals 12
• Five Final Risk Assessments

− Three final assessments indicated risks

• Trichloroethylene (TCE) – degreaser, spray fixative, stain remover 

• Methylene Chloride (MC) or Dichloromethane – paint remover

• NMP – paint remover

− Two final assessments did not indicate risks

• 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8,-hexamethylcyclopenta-[γ]-2-

benzopyran (HHCB) – fragrance in products

• Antimony Trioxide (ATO) – synergist in halogenated flame retardants

• Risk reduction actions, both voluntary and regulatory, 

are underway for TCE, MC and NMP

Completed Assessments

TSCA WORK PLAN: ASSESSMENTS

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Trichloroethylene (TCE)

EPA identified risks associated with commercial and 

consumer uses of TCE in vapor and aerosol degreasers, 

and with use as a spotting agent in dry cleaning

− Acute exposure can affect developing fetus; high acute 

exposure can irritate the respiratory system and skin, and 

induce central nervous system effects

− Chronic exposure is associated with adverse effects in liver, 

kidneys, immune system, reproductive system, and 

developing fetuses. Also carcinogenic in humans

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https://www.epa.gov/assessing-and-managing-chemicals-undertsca/tsca-work-plan-chemical-risk-assessment

TSCA WORK PLAN: ASSESSMENTS
NMP and Methylene Chloride

EPA identified risks associated with commercial 

and consumer paint and varnish remover uses

− NMP - Developmental toxicity effects including low 

birthweight, growth retardation and fetal death are 

associated with certain uses

− Methylene chloride - A volatile organic compound 

that has acute effects including confusion, 

incapacitation and death. Also classified as a likely 

human carcinogen

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https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/tsca-work-plan-chemicalrisk-assessment-n-0

https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/tsca-work-plan-chemicalrisk-assessment-methylene

TSCA WORK PLAN: ASSESSMENTS
DRAFT Risk Assessment for Work Plan 

Chemical: 1-Bromopropane

• released for public comment & peer review March 2016

• Occupational uses in spray adhesives, dry-cleaning & degreasing 

operations

• Occupational and Consumers 

• Effects on human health only

• https://www.epa.gov/assessing-and-managing-chemicals-undertsca/tsca-work-plan-chemical-risk-assessment-peer-review

• Public Comments accepted until May 8, 2016 @ EPA Docket: EPAHQ-OPPT-2015-0084

• Public Comments accepted until May 10 @ EPA Docket: EPA-HQOPPT-2015-0805 or by submission to Designated Federal Official

TSCA WORK PLAN: ASSESSMENTS

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Completed Work Plan Chemical 

Problem Formulation & Initial Assessments

• 1,4-Dioxane

− Problem formulation on uses as a solvent & effects on human health

• Flame Retardants 

− Brominated Phthalates Cluster (TBB & TBPH)

• Data Needs Assessment: polyurethane foams

− Tetrabromo Bisphenol A Cluster (TBBPA)

• Problem Formulation: plastics/printed circuit boards for electronics

− Cyclic Aliphatic Bromides Cluster (HBCD)

• Problem Formulation: extruded and expanded polystyrene foam 

and polystyrene products

− Chlorinated Phosphate Esters Cluster (TCEP)

• Problem Formulation: furniture foams and textiles

TSCA WORK PLAN: ASSESSMENTS

https://www.epa.gov/assessing-and-managing-chemicals-undertsca/assessments-tsca-work-plan-chemicals | 17
• Problem Formulation & Initial Assessments in 

FY16-17

− Pigments 

− Chlorinated Solvents

• 1,1-Dichloroethane

• 1,2-Dichloroethane

• 1,2-Dichloropropane

• Trans-1,2-Dichloroethylene

• 1,1,2-Trichloroethane

• Carbon Tetrachloride

• Tetrachloroethylene (PERC)

TSCA WORK PLAN: ASSESSMENTS

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OPPT’s Risk Assessment 

Process

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SCOPING OF DATA & INFORMATION FOR RISK

ASSESSMENT

• Gather, review and organize data and information on 

chemical uses, exposure: frequency, duration, & 

magnitude, ecological and health hazard data to be 

− Sources: Manufacture/Import and Uses

− Exposure Pathways and Receptors 

− Hazard Data: Hazard Values, Dose-Response

Hazard

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NOT ALL ASSESSMENTS ARE CREATED EQUAL

• “Fit for Purpose”

• Manufacture, Process & Uses Assessed

• Chemical-Specific Uses define:

− Exposure Pathways/Routes

• Air, Water, Sediment, Soil, Fish

• Inhalation, Oral, Dermal

− Receptors/Populations 

• Occupational 

• General population 

• Consumer exposures

• Environment/Ecological

• Only Existing/Available Data are used

• Problem Formulation is critical first step

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• 1983: NAS “Red Book*” frame the Risk Assessment 

Paradigm:

– Risk Assessment = Haz ID + Dose-Response and Exposure 

Assessment

• 1992/1998: EPA’s Guidelines for Ecological Risk 

Assessment explicitly incorporated Problem 

Formulation into the Risk Assessment Paradigm

– 1992: Framework

– 1998: Final Publication

• 2011: NRC “Silver Book” recognized/affirmed the 

Importance of Problem Formulation and 

recommended to be integrated into Human Health risk 

Assessment paradigm in 2011

• 2014: EPA Incorporated into Framework for Human 

Health Risk Assessment 

PROBLEM FORMULATION

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PROBLEM FORMULATION

Problem Formulation

• EPA uses problem formulation to determine the extent 

to which data and tools are available to support the 

analysis

• Outcomes of Problem Formulation:

− Conceptual Model – including a visual 

representation and written description of actual or 

predicted relationships between chemicals and 

human or wildlife, and

− Analysis Plan – describing the intentions regarding 

the technical aspects of the risk assessment

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Planning 

(Risk Assessor/ 

Risk Manager 

Dialogue)

PROBLEM 

FORMULATION

Integrate Available Information

Source and 

Exposure 

Characteristics

Populations 

Potentially at 

Risk

Effects

Assessment 

Endpoints

Conceptual 

Model

Analysis 

Plan

ANALYSIS

PROBLEM FORMULATION

ANALYSIS

RISK CHARACTERIZATION

Data, Iterate Process, 

As Necessary: Acquire 

Monitor Results

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Example of a Generalized Conceptual Model With Examples of Possible Dimensions 

and Linkages 

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Combined

Commercial and 

Residential Uses 

of HHCB*

Wastewater Treatment Plant

HHCB in Surface Water

• Streams at Outfall Sites

• Lakes

• Estuaries, Marine

HHCB in Sediment

HHCB in Biosolids for 

Land Application

HHCB in Soil

HHCB in

Effluent

HHCB in

Sludge

Soil Toxicity

• Soil Invertebrates

• Plants

Aquatic Toxicity

(acute and chronic)

• Fish

• Invertebrates

• Plants

Sediment Toxicity

(chronic)

• Benthic Invertebrates

*Includes all fragranced products such as soaps, detergents, fabric 

softeners, shampoos, cosmetics, and cleaners.

EXPOSURES HAZARDS

Conceptual Model from Problem Formulation

Example from HHCB Assessment

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LEGEND 

• Solid lines = Pathway can be quantified

• Dashed lines = Pathway out of scope, not quantified

• Shaded boxes/ovals = Elements proposed for inclusion in risk 

assessment; exposure and toxicity can be quantified

SOURCES

Consumer: 

Paint Strippers

EXPOSURE PATHWAYS HUMAN RECEPTORS

Dose

EFFECTS

Consumers

Inhalation

, Dermal

Occupational: 

Paint Strippers

Air/Vapor, 

Direct 

Contact

Air/Vapor, 

Direct 

Contact

Workers Occupational: 

Coatings, 

Electronics, 

Petrochemical, 

Process Solvents 

Agricultural Crops Food Crops Ingestion General 

Population

Consumer:

Cleaning Products

Air/Vapor, 

Direct 

Contact

Inhalation

, Dermal

Air/Vapor, 

Direct 

Contact

Inhalation

, Dermal

Inhalation

, Dermal

Chronic Risks

Developmental 

Toxicity: Fetal 

Mortality

Acute Risks

Body Weight 

Reductions

Liver/ Kidney 

Effects

Clinical 

Chemistry

Neurotoxicity

Developmental 

Toxicity: Reduced 

Fetal Body 

Weight/Mortality

Reproductive 

Toxicity

Conceptual Model from Problem Formulation 

Example from N-methylpyrrolidone Assessment

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Conceptual Model from Problem Formulation

Example from HBCD Assessment
OCSPP SYSTEMATIC REVIEW FRAMEWORK - OVERVIEW

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DATA EVALUATION

When determining or evaluating the strengths and limitations of toxicity, clinical and 

epidemiological studies, numerous criteria are considered, including but not limited 

to the following:

• adequacy of study design (Fit-for-Purpose)

• test substance identification (e.g., purity, analytical confirmation of stability 

and concentration),

• information about test animals (e.g., species, source, sex, 

age/lifestage/embryonic stage) and relevance to the endpoint(s) of interest,

• number of subjects in each dose/concentration group,

• dosing regimen (e.g., dose/concentration levels and controls including 

solvent controls),

• timing and duration of exposure, and relevance to the endpoint(s) of 

interest,

• route/type of exposure,

• test conditions (e.g., husbandry, culture medium), 

• endpoints evaluated (e.g., schedule of observations, randomization and 

blinding procedures, assessment methods),

• reporting (quality and completeness)

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CONSIDERATIONS FOR REVIEWING DATA

QUALITY IN EPIDEMIOLOGICAL DATA

Study Population -Recruitment Strategy, inclusion/exclusion criteria

-Number, time period, age/sex/other distribution, geographic area

-Participation rates (at each stage), eligibility, comparison group selection, attrition 

rate

-Follow up

-Comparability (exposed and non-exposed)

Exposure -Specific substance measured, analytical methods

-Types of samples collected (matrix)

-Exposure groups defined, methods to assign

-Limit of detection or level of quantitation, number of samples above/below

-Exposure distribution (central tendency, range, etc)

-Potential for exposure misclassification 

-Use of TWAs for occupational studies

-Empirical, estimated, or modeled exposures

-Timing of collection

-Validation of biomarkers 

Statistical 

Analysis

-Power

-Appropriateness of methods used

-Reliable, consistent

-Treatment of non-detects or < LOQ

-Adjustment of variables

-Explicit presentation of results

-Significance levels clearly defined

Outcome -Novel or validated assessment tools, appropriateness for study population

-Blinding

-Explicit, complete presentation of results

-Timing

-Confounding

-Concordance of text with data results in tables

-Potential bias | 33
EXPOSURE ASSESSMENT

Chemical Specific Factors

• Physical chemical properties

− Solubility in water (log kow)

− Volatility/vapor pressure @ 20oC

− Melting point

• Environmental Fate

− 1⁄2 life in environmental media

• Persistence 

− Abiotic and Biotic breakdown

• Bioconcentration and Bioaccumulation

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EXPOSURE ASSESSMENT

Exposure Scenarios and Populations Assessed 

− Occupational: manufacturing and processing; chemicalspecific

− General population 

− Consumer exposures: use specific

Exposure Characterization

− Duration

− Pattern

− Route of Exposure

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EXPOSURE ASSESSMENT: FIT FOR PURPOSE

Fit for purpose hazard or risk?

− Emergency response guidance e.g., AEGLs

− National assessment 

− Site specific assessment

Acute typically time weighted average (TWA)

− Occupational 8 hr TWA

− Consumer 24 hr TWA

− General population 1-24 hr TWA (e.g., fence line, drinking 

water, fish consumption)?

Chronic scenarios typically for occupational but may 

include general population and consumers

− Average daily dose

− Life-time average daily dose

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EXPOSURE CALCULATION: ACUTE

Acute exposures are estimated as follows:

AC =

C×ED

AT

where:

− AC = acute concentration (8-hr TWA)

− C = contaminant concentration in air (8-hr TWA)

− ED = exposure duration (8-hr/day)

− AT = averaging time (8-hr/day)

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Average Daily Concentration (ADC) and Lifetime Average Daily Concentration (LADC) 

are used to estimate workplace exposures for non-cancer and cancer risks, 

respectively, as follows:

ADC or LADC =

C×ED×EF×WY

AT

where:

− ADC = average daily concentration (8-hr TWA) used for chronic non-cancer risk 

calculations

− LADC = lifetime average daily concentration (8-hr TWA) used for chronic 

cancer risk calculations

− C = contaminant concentration in air (8-hr TWA)

− ED = exposure duration (8 hr/day)

− EF = exposure frequency (260 days/yr)

− WY = working years per lifetime (40 yr)

− AT = averaging time (LT × 260 days/yr × 8 hrs/day; 

where LT = lifetime; LT = 40 yr for non-cancer risks; LT=70 yr for cancer risks)

• Parameters adjusted for consumers and general population 

exposures

EXPOSURE CALCULATIONS: CHRONIC

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EXPOSURE: DESCRIPTIVE MEASURES

Consumer/general 

population high end

Occupational high end 

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AGGREGATING EXPOSURES

• Data permitting, OPPT strives to aggregate exposures:

− Multiple Sources/Uses: 

• multiple occupational use scenarios

• multiple consumer products 

− Multiple pathways: dust is aggregate of uses; 

plus water ingestion and fish consumption 

− Multiple routes: dermal and inhalation

• Aggregate exposure assessments 

evaluate continued exposures to 

single chemical entity across 

multiple pathways and routes

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EFFECTS ASSESSMENT: EXPOSURE RELEVANCE

• Exposure Factors: e.g., Sex and Life-Stage Dependent 

• Biological Factors: Life-Stage Dependent

− Pharmacokinetic 

− Pharmacodynamics

• Acute Effects – Exposure Considerations

− Developmental

• Reversible (e.g., hypoxia, narcosis)

• Irreversible (e.g., lethality, terata)

• Latent expression

− Adult 

• Reversible (e.g., hypoxia, narcosis)

• Irreversible (e.g., lethality)

• Latent expression

• Chronic Exposures – Exposure Considerations

− Cancer and non-cancer

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HAZARD AND DOSE RESPONSE

• Choice of less than lifetime exposure studies (< 1/10 

the of lifespan) for chronic health effects Point of 

Departure (POD)/Uncertainty Factors (UFs)= RfV

− Typical of IRIS and PPRTV assessments

− Use developmental endpoints –resulting from short 

durations of exposure for chronic POD.

• Development of RfV’s or PODs for different durations

− EPA RfC/RfD Guidance Document

− EPA Children's Risk Assessment Framework

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HAZARD VALUE RELEVANT FOR

EXPOSURE SCENARIO

• A range of MOEs for acute and chronic risk estimates for 

respective exposure scenarios.

• For chronic exposure scenarios: a relatively low dose and 

short term/sub-chronic exposure can result in long-term 

adverse consequences. 

• For acute exposure scenarios: most sensitive endpoints 

are often development and/or reproductive endpoints 

(e.g., TCE and NMP developmental toxicity). 

− Supported by EPA policy. 

− Science-based policy based on the presumption that a single 

exposure of a chemical at a critical window of development 

can be adverse (EPA’s 1991 Guidelines for Developmental 

Toxicity Risk Assessment (pg. 38) and 1996 Guidelines for 

Reproductive Toxicity Risk Assessment (pg. 83)). 

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NON-CANCER DOSE-RESPONSE SUMMARY

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SCREENING LEVEL RISK ESTIMATION

QUANTIFYING NON-CARCINOGENIC HAZARD for HEALTH AND 

ECOLOGICAL RECEPTORS

The hazard or risk quotient (HQ/RQ) is the ratio of the exposure 

level at a site to the reference dose 

HEALTH HQ/RQ = Acute or Chronic Exposure (i.e., ADD/C)

Reference Value (POD/UFs)

ECO HQ/RQ = Acute or Chronic Exposure

Concentration of Concern

(NOAEL or LOAEL (POD/UFs))

• HQ/RQ values are variable, with values less than and equal to 1 

generally considered indicative of acceptable hazard 

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RISK CALCULATION

Non-Cancer MOE compared to benchmark MOE (UF)s

MMMMMMaaaaaaaaaa oooo cc cccc

=

NN − CC HH HH HH VVaaaaaaaa (PP PP)

HH HH EEEE EE

Where: 

− MOE = Margin of exposure (unitless)

− Hazard value (POD) = HEC or HED (ppm) 

− Risk estimate compared to Benchmark MOE (UFs) which is 

unacceptable risk level 

Risk No Risk

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RISK CALCULATION

Cancer

RR RR = HH HH EEEE EE × IIII

Where:

− Risk = Cancer risk (unitless)

− Human exposure = Exposure estimate (LADC in ppm) from 

occupational exposure assessment

− IUR = Inhalation unit risk (a x 10-x per ppm)

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Assessing Chemicals for Safety

Work Plan

Chemicals

Risk Action

(Voluntary, Regulatory)

No Risk No Action

Risk Assessment & Reduction

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SELECTED GUIDANCE WITH RELEVANCE

TO WORK PLAN RISK ASSESSMENTS

• 2014 Framework for Human Health Risk Assessment to Inform Decision Making

− 2011 Recommended Use of Body Weight 3/4 as the Default Method in Derivation of the 

Oral Reference Dose

− 2006 A Framework for Assessing Health Risk of Environmental Exposures to Children

− 2005 Guidelines for Carcinogen Risk Assessment-

− 2005 Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to 

Carcinogens

− 2002 A Review of the Reference Dose and Reference Concentration Processes

− 1998 Guidelines for Neurotoxicity Risk Assessment-

− 1996 Guidelines for Reproductive Toxicity Risk Assessment

− 1991 Guidelines for Developmental Toxicity Risk Assessment

• 1992 Guidelines for Exposure Assessment

− 2011 Exposure Factors Handbook 

− 2009 Guidance Document on the Development, Evaluation and Application of Environmental Models

− 2001 Summary Report of the Technical Workshop on Issues Associated with Considering Developmental 

Changes in Behavior and Anatomy When Assessing Exposure to Children

• 1998 Guidelines for Ecological Risk Assessment

• 2000 Risk Characterization Handbook

• 2015 Peer Review Handbook - 4th Edition

https://www.epa.gov/risk/risk-assessment-guidelines| 49
RESOURCES

To learn more about TSCA Work Plan 

Chemicals & Assessments: 

http://www2.epa.gov/assessing-and-managing-chemicals-undertsca/tsca-work-plan-chemicals

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