It Takes a Village to It Takes a Village to Raise a ChildRaise a Child

Roberta L. Grant, Ph.D.Roberta L. Grant, Ph.D.Toxicology Section - Chief Engineer’s OfficeToxicology Section - Chief Engineer’s OfficeTexas Commission on Environmental QualityTexas Commission on Environmental Quality

OutlineOutline

Toxicity assessmentsToxicity assessmentsChemicals with limited toxicity dataChemicals with limited toxicity dataChemicals with adequate toxicity dataChemicals with adequate toxicity data

Professional judgmentProfessional judgment

Interactive processesInteractive processes

Toxicity AssessmentToxicity Assessment

The basic objective of a toxicity The basic objective of a toxicity assessment is to identify what adverse assessment is to identify what adverse health effects a chemical causes and how health effects a chemical causes and how the appearance of these adverse effects the appearance of these adverse effects depends on exposure level (dose)depends on exposure level (dose)

General Paradigm for Risk Assessment

Hazard Identification

Dose Response Assessment

Exposure Assessment

Risk Characterization

U.S. Department of Health and Human Services

Risk Assessment

November 2006 November 2006 Guidelines to Develop Effects Screening Levels, Guidelines to Develop Effects Screening Levels,

Reference Values, and Unit Risk Factors Reference Values, and Unit Risk Factors RG-442RG-442

Effects Screening Levels (ESLs)Effects Screening Levels (ESLs)Chemical-specific air concentrations set to protect Chemical-specific air concentrations set to protect human health and welfare.human health and welfare.

Short-term ESLs are based on data concerning acute Short-term ESLs are based on data concerning acute health effects [1-hr intermittent], odor/nuisance health effects [1-hr intermittent], odor/nuisance potential, and vegetative effectspotential, and vegetative effects

Long-term ESLs [annual] are based on data Long-term ESLs [annual] are based on data concerning chronic non-carcinogenic and/or concerning chronic non-carcinogenic and/or carcinogenic health effects and vegetative effectscarcinogenic health effects and vegetative effects

This presentation will only discuss health-based ESLsThis presentation will only discuss health-based ESLs

Reference Values (ReVs) and ESLsReference Values (ReVs) and ESLs

Exposure to an air concentration at or below the Exposure to an air concentration at or below the ReV or ESL is not likely to cause adverse health ReV or ESL is not likely to cause adverse health effects in the general public, including sensitive effects in the general public, including sensitive subpopulations such assubpopulations such as::ChildrenChildrenPregnant womenPregnant womenElderlyElderlyIndividuals with pre-existing conditionsIndividuals with pre-existing conditions

ReVs and ESLs are screening values - not ReVs and ESLs are screening values - not standardsstandards

ReVs and ESLsReVs and ESLsUnit Risk FactorsUnit Risk Factors

For acute and chronic health effects with a For acute and chronic health effects with a threshold threshold

health-based ESLs = 0.3 x ReV health-based ESLs = 0.3 x ReV (cumulative and aggregate)(cumulative and aggregate)

For chronic health effects without a thresholdFor chronic health effects without a threshold

Derive a unit risk factor. Calculate a No Derive a unit risk factor. Calculate a No Significant Risk Level of 1 in 100,000 excess Significant Risk Level of 1 in 100,000 excess riskrisk

Texas Clean Air ActTexas Clean Air Act

Section 382.002 of the Section 382.002 of the Texas Health and Safety Texas Health and Safety Code empowers the TCEQCode empowers the TCEQ to to regulate ambient regulate ambient air conditions to protect human health, general air conditions to protect human health, general welfare, and physical property from impacts of welfare, and physical property from impacts of air pollution in the ambient air. air pollution in the ambient air.

The Texas Health and Safety Code is The Texas Health and Safety Code is comprehensive. ESLs are developed for as comprehensive. ESLs are developed for as many air contaminants as possible, even for many air contaminants as possible, even for chemicals with limited toxicity data.chemicals with limited toxicity data.

Tiered Approach for Chemicals Tiered Approach for Chemicals with Limited Toxicity Informationwith Limited Toxicity Information

Tier IEmission Controls

(Best-Available-Control Technology)Threshold of Regulation

default ESL = 1µg/m3

Time and Resource Requirements

Tox

icity

Info

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Com

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ity o

f Dec

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Tier IIIRelative Toxicity/Potency Approach

generic ESL

Tier IIThreshold of Concern Approach

Use LC50 Data

generic ESL

Threshold of Concern ApproachThreshold of Concern Approach

Threshold of Concern ApproachThreshold of Concern Approach

Obtain LCObtain LC5050 data and acute inhalation NOAELs data and acute inhalation NOAELs from animal studies for 97 chemicalsfrom animal studies for 97 chemicals

Categorize chemicals into different acute Categorize chemicals into different acute inhalation toxicity potency classes using LCinhalation toxicity potency classes using LC5050 data and the Globally Harmonized System data and the Globally Harmonized System (GHS) of Classification and Labeling of (GHS) of Classification and Labeling of Chemicals (United Nations 2005)Chemicals (United Nations 2005)

Threshold of Concern (TOC)Threshold of Concern (TOC)Table 3-3. Threshold of Concern Approach for Determining Tier II Generic Short-Term ESLs• Globally Harmonized System of Classification and Labeling of Chemicals (GHS)

• Category 1 • Category 2 • Category 3 • Category 4 • Category 5

• Skin Irritation • Corrosive • Irritant • Mild Irritant

• Eye Irritation • Causes serious eye damage

• Causes serious eye irritation

• Causes mild to moderate eye irritation d

Oral LD50

mg/kg

0 to < 5 a > 5 to < 50 a > 50 to < 300 a > 300 to < 2000 a > 2,000 a

• LC50

• gas• ppmv

• 0 to < 100 • > 100 to < 500 • > 500 to < 2500 • > 2500 to < 5000 • > 5,000

LC50

dust & mists b

• mg/m3

• 0 to < 50 • > 50 to < 500 • > 500 to < 1000 • > 1000 to < 5000 • > 5,000

• LC50

• vapors c

• mg/m3

• 0 to < 500 • > 500 to < 2000

• > 2000 to < 10,000 • > 10,000 to < 20,000 • > 20,000

• Generic Short-Term ESL

• 4 µg/m3 • 20 µg/m3 • 125 µg/m3 • 125 µg/m3 • 1000 µg/m3

Cat 3&4 =12.6 mg/m3

Cat 5 = 104 mg/m3Cat 2 = 2 mg/m3

Cat 1 = 0.4 mg/m3

Calculate the 10th percentile of the cumulative Calculate the 10th percentile of the cumulative percentage distribution of NOAELs in each categorypercentage distribution of NOAELs in each category

Threshold of Concern (TOC)Threshold of Concern (TOC)

Divide the 10Divide the 10thth percentile NOAEL values by percentile NOAEL values by 100 to account for human variability and 100 to account for human variability and uncertainty of animal to human extrapolationuncertainty of animal to human extrapolation

Cat 1: 0.4 mg/m3 / 100 = 4 ug/m3

Cat 2: 2 mg/m3 / 100 = 20 ug/m3

Cat 3&4: 12.6 mg/m3 / 100 = 125 ug/m3

Cat 5: 104 mg/m3 / 100 = 1000 ug/m3

Use the LCUse the LC5050 data of a chemical to categorize it data of a chemical to categorize it into a GHS category. Use the TOC for that into a GHS category. Use the TOC for that category as a generic ESLcategory as a generic ESL

Tier II Generic ESLsTier II Generic ESLsNOAEL to LCNOAEL to LC5050 Ratio Approach Ratio Approach

NOAEL-to-LCNOAEL-to-LC5050 Ratio Ratio

10th percentile ratio = 0.0083

Calculate the ratio between acute inhalation NOAELs and LC50

Calculate the 10th percentile ratio

NOAEL-to-LCNOAEL-to-LC5050 Ratio Ratio

Divide the ratio of 0.0083 by 100 to Divide the ratio of 0.0083 by 100 to account for human variability and account for human variability and uncertainty of animal to human uncertainty of animal to human extrapolationextrapolation

Health-Protective Ratio = 0.000083Health-Protective Ratio = 0.000083

LCLC5050 data x 0.000083 = data x 0.000083 =

generic ESLgeneric ESL

TOC or TOC or NOAEL-to- LCNOAEL-to- LC5050 Ratio Approach? Ratio Approach?Both approaches use LCBoth approaches use LC5050 data, although the data, although the TOC approach is generally more conservative TOC approach is generally more conservative than the NOAEL-to- LCthan the NOAEL-to- LC5050 Ratio approach Ratio approach

Use information on the chemical and a weight-Use information on the chemical and a weight-of-evidence approach to decide which approach of-evidence approach to decide which approach is most defensibleis most defensible

Choose the most conservative number if there is Choose the most conservative number if there is uncertainty in the quality of the LC uncertainty in the quality of the LC5050 data data

Chemicals with Adequate Toxicity DataChemicals with Adequate Toxicity Data

Review essential data including physical/ chemical Review essential data including physical/ chemical properties and select key studiesproperties and select key studies

Conduct a Mode of Action (MOA) analysisConduct a Mode of Action (MOA) analysis

(threshold or nonthreshold)(threshold or nonthreshold)

Choose the appropriate dose metricChoose the appropriate dose metric

Determine the Point of Departure (POD) for each Determine the Point of Departure (POD) for each key studykey study

Conduct appropriate dosimetric modelingConduct appropriate dosimetric modeling

Chemicals with Adequate Toxicity DataChemicals with Adequate Toxicity Data

Extrapolate from the adjusted POD to lower exposures Extrapolate from the adjusted POD to lower exposures based on MOA analysis and select critical effectbased on MOA analysis and select critical effect

For health effectsFor health effects with thresholdswith thresholds

For health effects For health effects without a thresholdwithout a threshold

(typically carcinogens) (typically carcinogens)

DLSubAH

[HEC]

UFUFUFUFUF

PODReV

THE FOUNDATIONTHE FOUNDATION

Scientific dataScientific data

Trained toxicologists and other scientistsTrained toxicologists and other scientists

Accepted scientifically-based procedures and Accepted scientifically-based procedures and guidelinesguidelines

Professional judgmentProfessional judgment

Public commentPublic comment

The Role of Professional JudgmentThe Role of Professional Judgment

Judgment should be based on science and common sense

Difficult pill for society to swallow

Would you trust a bureaucrat to use judgment? Society as a whole Does Not!

With judgment comes responsibility

Professional Judgment and BalanceProfessional Judgment and Balance

“We must not only get the correct result, we must do so in a manner that promotes public acceptance of the result”

Vincent Cogliano

International Agency for Research on Cancers

2007 Toxicology and Risk Assessment Conference

Interactive ProcessesInteractive Processes

Scientists

Industrial hygienists and scientists – the regulated community

Academic researchers

Citizens and environmental groups

Regulators and Risk Managers

Consultants,

specialists

Interactive Processes Outlined in Interactive Processes Outlined in RG-442 ESL GuidelinesRG-442 ESL Guidelines

A Toxicity Value is BornA Toxicity Value is Born

Chemicals for which we will develop ESLs Chemicals for which we will develop ESLs will be posted on the TCEQ website will be posted on the TCEQ website

Draft Development Support Document Draft Development Support Document (DSD)(DSD)

The draft DSD becomes a proposed DSDThe draft DSD becomes a proposed DSD

Interactive ProcessesInteractive ProcessesThe Village - Public Comment PeriodThe Village - Public Comment Period

The proposed DSDs are posted on the The proposed DSDs are posted on the TCEQ website for a 60- or 90-day public TCEQ website for a 60- or 90-day public comment periodcomment period

Public information meetings in AustinPublic information meetings in Austin

Interactive ProcessesInteractive ProcessesRaising the ChildRaising the Child

Public comments are receivedPublic comments are received

The final DSD and response to comments The final DSD and response to comments are posted on the TCEQ websiteare posted on the TCEQ website

TransparencyTransparency

Interactive Processes Interactive Processes External Scientific Peer ReviewsExternal Scientific Peer Reviews

External scientific peer reviews External scientific peer reviews

RG-442 ESL Guidelines did undergo RG-442 ESL Guidelines did undergo external scientific peer review and public external scientific peer review and public commentcomment

Occasionally, the TCEQ will conduct a Occasionally, the TCEQ will conduct a peer review for an individual DSDpeer review for an individual DSD

(example: 1,3-butadiene)(example: 1,3-butadiene)

SummarySummary

The TCEQ conducts toxicity assessments to The TCEQ conducts toxicity assessments to develop ESLs, ReVs, and URFs. ESLs and develop ESLs, ReVs, and URFs. ESLs and ReVs are health-protective screening levels ReVs are health-protective screening levels whereas URFs are factors used to calculate whereas URFs are factors used to calculate air concentrations at the No Significant Risk air concentrations at the No Significant Risk Level of one in 100,000 excess risk Level of one in 100,000 excess risk

SummarySummary

For chemicals with limited toxicity data, For chemicals with limited toxicity data, statistical or relative toxicity/potency statistical or relative toxicity/potency approaches can be used to derive health-approaches can be used to derive health-protective default or generic ESLsprotective default or generic ESLs

Tier 1 – Threshold of RegulationTier 1 – Threshold of Regulation Tier II – Threshold of Concern and NOAEL-to-LCTier II – Threshold of Concern and NOAEL-to-LC5050 Ratio Ratio

Tier III – Relative Toxicity/Potency ApproachTier III – Relative Toxicity/Potency Approach

SummarySummary

For chemicals with adequate toxicity data, For chemicals with adequate toxicity data, the foundation of a sound toxicity the foundation of a sound toxicity assessment is toxicity data, scientifically- assessment is toxicity data, scientifically- defensible procedures, professional defensible procedures, professional judgment, balance, and interactive judgment, balance, and interactive processesprocesses

SummarySummary

It takes a community of scientists and It takes a community of scientists and specialists as well as the regulated specialists as well as the regulated community and concerned citizens community and concerned citizens engaged in a dynamic interactive process engaged in a dynamic interactive process to produce a publicly acceptable toxicity to produce a publicly acceptable toxicity assessmentassessment

QuestionsQuestions

Roberta L. GrantRoberta L. Grantrgrantrgrant@tceq.state.tx.us@tceq.state.tx.us

(512) 239-4115(512) 239-4115

Toxicology Section Website:Toxicology Section Website:http://www.tceq.state.tx.us/implementation/tox/esl/guidelines/http://www.tceq.state.tx.us/implementation/tox/esl/guidelines/

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