Assessing Dose and Potency of Chemicals Robert Blaisdell, Ph.D, Chief Exposure Modeling Section Office of Environmental Health Hazard Assessment.

Assessing Dose and Assessing Dose and Potency of ChemicalsPotency of Chemicals

Robert Blaisdell, Ph.D, ChiefRobert Blaisdell, Ph.D, ChiefExposure Modeling SectionExposure Modeling Section

Office of Environmental Health Hazard Office of Environmental Health Hazard AssessmentAssessment

Air Programs Using Risk Assessment Air Programs Using Risk Assessment Information in CaliforniaInformation in California

Toxic Air Contaminant Program. Chemical Toxic Air Contaminant Program. Chemical specific risk assessments (developed by specific risk assessments (developed by OEHHA) and emission data, exposure OEHHA) and emission data, exposure assessment (ARB) are to used to inform Air assessment (ARB) are to used to inform Air Toxics Control Measures (ATCMs) (180 Toxics Control Measures (ATCMs) (180 chemicals).chemicals).

ATCMs are industry-wide requirements for air ATCMs are industry-wide requirements for air pollution control (ARB). pollution control (ARB).

Chemical specific risk assessment (dose-Chemical specific risk assessment (dose-response assessment) allows prioritization so response assessment) allows prioritization so that high risk industries are addressed (e.g that high risk industries are addressed (e.g diesel emitters, dry cleaners and metal platers).diesel emitters, dry cleaners and metal platers).

Air Programs Using Risk Air Programs Using Risk Assessment Information in CaliforniaAssessment Information in California

The Hot Spots Program uses both chemical-The Hot Spots Program uses both chemical-specific risk assessment and exposure assessment specific risk assessment and exposure assessment to address air pollution from stationary sources to address air pollution from stationary sources (~400 chemicals). (~400 chemicals).

Facilities must report emissions every four years.Facilities must report emissions every four years. Facilities that may pose a threat to public health are Facilities that may pose a threat to public health are

required to do a risk assessment.required to do a risk assessment. Facilities are required to notify the exposed public if Facilities are required to notify the exposed public if

the risks are above a certain level.the risks are above a certain level. Info is used in the Risk Reduction and Audits Info is used in the Risk Reduction and Audits

program to require additional pollution control program to require additional pollution control devices on high risk facilities.devices on high risk facilities.

How is Chemical Risk Assessment How is Chemical Risk Assessment Done?Done?

Hazard Identification—Do the chemicals in Hazard Identification—Do the chemicals in question pose a potential risk?question pose a potential risk?

Exposure assessment—How much of the Exposure assessment—How much of the chemical are people exposed to? chemical are people exposed to?

Dose-Response Evaluation—What is the Dose-Response Evaluation—What is the relationship between the dose of the relationship between the dose of the chemical and the health effect?chemical and the health effect?

Risk Characterization—What is the risk Risk Characterization—What is the risk from the facility?from the facility?

Noncancer Health Effects Dose-Noncancer Health Effects Dose-ResponseResponse

It is generally accepted that there is a threshold It is generally accepted that there is a threshold or level of exposure at or below which or level of exposure at or below which noncancer health effects will not occur. noncancer health effects will not occur.

Noncancer health values are designed to be Noncancer health values are designed to be “safe” levels where health impacts are not “safe” levels where health impacts are not expected even in sensitive members of the expected even in sensitive members of the general population. general population.

Limited number of chemicals have been Limited number of chemicals have been considered due to lack of resources and data.considered due to lack of resources and data.

Non Cancer Health Effects Dose-Non Cancer Health Effects Dose-Response Response

Multiple noncancer health effects on different Multiple noncancer health effects on different organ systems can occur with one chemical at organ systems can occur with one chemical at different doses. different doses.

Human and animal toxicology studies are Human and animal toxicology studies are reviewed and the health effect occurring at the reviewed and the health effect occurring at the lowest dose is selected as the basis for the REL.lowest dose is selected as the basis for the REL.

A No Observed Adverse Effect Level (NOAEL) A No Observed Adverse Effect Level (NOAEL) or Lowest Observed Adverse Effect Level or Lowest Observed Adverse Effect Level (LOAEL) is determined from the study. (LOAEL) is determined from the study.

Benchmark dose applies a statistical approach Benchmark dose applies a statistical approach to estimate REL. to estimate REL.

Reference Exposure LevelReference Exposure Level

Chronic inhalation REL—a “safe” air Chronic inhalation REL—a “safe” air concentration (concentration (µg/mµg/m33)) for continuous for continuous inhalation exposure (80 chemicals).inhalation exposure (80 chemicals).

Acute inhalation REL—a “safe” air Acute inhalation REL—a “safe” air concentration (concentration (µg/mµg/m33)) for 1 hour infrequent for 1 hour infrequent exposures (52 chemicals).exposures (52 chemicals).

Oral Chronic REL—a “safe” level of Oral Chronic REL—a “safe” level of exposure through the oral route (mg/kg exposure through the oral route (mg/kg body weight/day) [7 chemicals].body weight/day) [7 chemicals].

Reference Exposure LevelReference Exposure Level

Uncertainty factors are used to ensure that the Uncertainty factors are used to ensure that the noncancer health value will be below the noncancer health value will be below the threshold. Typical uncertainty factors include:threshold. Typical uncertainty factors include: 10 X for animal to human.10 X for animal to human. 10X if short term study is used for a chronic REL.10X if short term study is used for a chronic REL. 10X currently for variability in the human population.10X currently for variability in the human population. 10 X if a LOAEL is used instead of a NOAEL.U10 X if a LOAEL is used instead of a NOAEL.U

Uncertainty factors are multiplied together and Uncertainty factors are multiplied together and are not usually higher than 3000.are not usually higher than 3000.

Exceeding the REL means the likelihood of Exceeding the REL means the likelihood of health effects is increased but does not health effects is increased but does not necessarily mean that they will occur. necessarily mean that they will occur.

Cancer Potency FactorsCancer Potency Factors Cancer-causing Chemicals (carcinogens) are Cancer-causing Chemicals (carcinogens) are

not considered to have a threshold below which not considered to have a threshold below which there is no risk. there is no risk.

Animal studies or human epidemiological studies Animal studies or human epidemiological studies (usually workers) are used to estimate the (usually workers) are used to estimate the relationship between dose and excess cancer relationship between dose and excess cancer risk. risk.

The cancer potency factor is the slope of that The cancer potency factor is the slope of that dose-response relationship (121 chemcals).dose-response relationship (121 chemcals).

The dose (mg/kg-day) is multiplied X the cancer The dose (mg/kg-day) is multiplied X the cancer potency factor [1/(mg/kg-day)] to give cancer potency factor [1/(mg/kg-day)] to give cancer risk. risk.

Cancer Risk EstimationCancer Risk Estimation

Cancer risk can be defined as the excess risk of Cancer risk can be defined as the excess risk of getting cancer with a 24 hour/day exposure to a getting cancer with a 24 hour/day exposure to a given daily dose of a chemical for 70 years.given daily dose of a chemical for 70 years.

1 X 101 X 10-6-6 (1 in a million) cancer risk means that if (1 in a million) cancer risk means that if a million people are exposed, one additional a million people are exposed, one additional cancer case would be expected. cancer case would be expected.

The level of cancer risk considered acceptable The level of cancer risk considered acceptable or de minimus is politically determined. It varies or de minimus is politically determined. It varies in different programs from 1 X 10in different programs from 1 X 10-6-6 to 1 X 10 to 1 X 10-4 -4 (1 (1 per million to 100 per million).per million to 100 per million).

Cancer RiskCancer Risk

The background lifetime risk of getting The background lifetime risk of getting allall types of cancer is around 1 in 3 to 1 in 4.types of cancer is around 1 in 3 to 1 in 4.

The inhalation cancer risk from breathing The inhalation cancer risk from breathing the general air pollution in the South Coast the general air pollution in the South Coast is somewhere around 700 in a million.is somewhere around 700 in a million.

The acceptable cancer risk from stationary The acceptable cancer risk from stationary facilities, as determined by the local Air facilities, as determined by the local Air Pollution Control District is generally 10 in Pollution Control District is generally 10 in a million for lifetime exposures.a million for lifetime exposures.

Exposure Assessment of Airborne Exposure Assessment of Airborne ChemicalsChemicals

The amount of chemical emitted from a The amount of chemical emitted from a stationary facility, freeway or rail yard can stationary facility, freeway or rail yard can be estimated.be estimated.

The dispersion of the chemical can be The dispersion of the chemical can be estimated using local meteorological data estimated using local meteorological data and a computer air model. and a computer air model.

Exposure Assessment of Airborne Exposure Assessment of Airborne ChemicalsChemicals

Air modeling techniques have been validated Air modeling techniques have been validated with air monitoring and are generally considered with air monitoring and are generally considered to be accurate within about a factor of 2.to be accurate within about a factor of 2.

Accuracy in a given situation is dependent on Accuracy in a given situation is dependent on terrain, applicability of the meteorological data to terrain, applicability of the meteorological data to the site and other factors. the site and other factors.

Modeling of multiple facilities, complex facilities, Modeling of multiple facilities, complex facilities, freeways, etc within a small region is currently freeways, etc within a small region is currently feasible with high end desktop computers. feasible with high end desktop computers.

Exposure Assessment of Airborne Exposure Assessment of Airborne ChemicalsChemicals

Many airborne chemicals are gases and Many airborne chemicals are gases and exposure only occurs by inhalation. exposure only occurs by inhalation.

The ground level air concentrations as well The ground level air concentrations as well as the deposition of metals and as the deposition of metals and semivolatile organic chemicals onto to soil semivolatile organic chemicals onto to soil or plants can be modeled. or plants can be modeled.

Exposure Assessment of Airborne Exposure Assessment of Airborne ChemicalsChemicals

Inhalation exposure can be estimated by using a Inhalation exposure can be estimated by using a daily breathing rate and the air concentration. daily breathing rate and the air concentration.

Estimation of noninhalation routes of exposure Estimation of noninhalation routes of exposure to metals and semivolatile organic chemicals to metals and semivolatile organic chemicals deposited into soil is more complex (and less deposited into soil is more complex (and less certain).certain).

Exposure to these chemicals may occur by Exposure to these chemicals may occur by inadvertent soil ingestion, consumption of home inadvertent soil ingestion, consumption of home grown produce, meat, contaminated surface grown produce, meat, contaminated surface water (as a drinking water source), mother’s water (as a drinking water source), mother’s milk, or from skin contact with contaminated soil milk, or from skin contact with contaminated soil or surfaces. or surfaces.

Site-Specific Exposure AssessmentSite-Specific Exposure Assessment

Estimates of the dose that an individual is Estimates of the dose that an individual is exposed from all the pathways that occur exposed from all the pathways that occur at particular site can be made. at particular site can be made.

The procedures in the Hot Spots risk The procedures in the Hot Spots risk assessment guidelines will tend to assessment guidelines will tend to overestimate rather than underestimate overestimate rather than underestimate exposure (and thus dose) in order to exposure (and thus dose) in order to protect public health. protect public health.

Risk Characterization for the Hot Risk Characterization for the Hot Spots program--Cancer RiskSpots program--Cancer Risk

The dose of the emitted carcinogens are The dose of the emitted carcinogens are estimated using standardized exposure estimated using standardized exposure parameters. parameters.

The estimated doses are multiplied times the The estimated doses are multiplied times the cancer potency factors to give cancer risk for cancer potency factors to give cancer risk for each chemical. each chemical.

Cancer risks from all emitted carcinogens are Cancer risks from all emitted carcinogens are summed. summed.

Carcinogens without sufficient data for cancer Carcinogens without sufficient data for cancer potency slopes cannot be evaluated. potency slopes cannot be evaluated.

Risk Characterization for Hot Spots Risk Characterization for Hot Spots Program-Noncancer Health EffectsProgram-Noncancer Health Effects A noncancer hazard quotient is A noncancer hazard quotient is

determined by dividing the modeled air determined by dividing the modeled air concentration by the REL. concentration by the REL.

The hazard index is the sum of all hazard The hazard index is the sum of all hazard quotients for all chemicals emitted that quotients for all chemicals emitted that impact a particular organ system. impact a particular organ system.

Risk Characterization-Hot SpotsRisk Characterization-Hot Spots A chemical may be a carcinogen and/or cause A chemical may be a carcinogen and/or cause

noncancer health effects. noncancer health effects. The cancer and noncancer risks are determined The cancer and noncancer risks are determined

for the following receptors:for the following receptors: The Residential Maximally Exposed Individual—the The Residential Maximally Exposed Individual—the

existing residence with the highest noncancer and existing residence with the highest noncancer and cancer risk (could be different locations for noncancer cancer risk (could be different locations for noncancer and cancer risk).and cancer risk).

The Maximally Exposed Individual Worker—this is for The Maximally Exposed Individual Worker—this is for offsite workers.offsite workers.

The Maximally Exposed Individual—the point with The Maximally Exposed Individual—the point with highest risk offsite.highest risk offsite.

Public Comment and Peer ReviewPublic Comment and Peer Review

OEHHA’s chemical specific risk assessment and OEHHA’s chemical specific risk assessment and exposure assessment documents are released exposure assessment documents are released for public comment.for public comment.

There is a formal response to public comment There is a formal response to public comment and revision of the document.and revision of the document.

The State’s Scientific Review Panel on Toxic Air The State’s Scientific Review Panel on Toxic Air Contaminants then reviews and endorses the Contaminants then reviews and endorses the documents.documents.

This process, although lengthy, helps ensure the This process, although lengthy, helps ensure the scientific validity of risk assessment procedures. scientific validity of risk assessment procedures.

Concerns about Risk AssessmentConcerns about Risk Assessment

The first administrator of USEPA The first administrator of USEPA compared risk assessment to a captured compared risk assessment to a captured spy. If you torture it long enough it would spy. If you torture it long enough it would tell you anything. tell you anything.

Comment: “Gaming” can be minimized with Comment: “Gaming” can be minimized with standardized procedures for emissions standardized procedures for emissions estimation, air modeling, dose response and estimation, air modeling, dose response and exposure assessment, and oversight, such as exposure assessment, and oversight, such as we have in California’s Hot Spots program. we have in California’s Hot Spots program.

Concerns About Risk AssessmentConcerns About Risk Assessment

Communities often do not have the expertise to Communities often do not have the expertise to use the tools or verify the results, or the use the tools or verify the results, or the resources to hire experts to evaluate the results. resources to hire experts to evaluate the results.

Risk assessment has been used to look at one Risk assessment has been used to look at one facility at a time and does not consider the entire facility at a time and does not consider the entire burden of multiple facilities. This can a particular burden of multiple facilities. This can a particular problem in environmental justice communities problem in environmental justice communities with mixed residential-industrial zoning and bad with mixed residential-industrial zoning and bad historical land use decisions. historical land use decisions. Comment: Risk assessment now has the capability of Comment: Risk assessment now has the capability of

modeling multiple sources, unlike a few years ago. modeling multiple sources, unlike a few years ago.

Concerns About Risk AssessmentConcerns About Risk Assessment

The current toxicological scientific body of The current toxicological scientific body of literature is inadequate. Basic literature is inadequate. Basic toxicological Information is lacking on toxicological Information is lacking on many chemicals in current use.many chemicals in current use. Comment: Yes a serious problem for those Comment: Yes a serious problem for those

chemicals lacking data. chemicals lacking data.

Concerns About Risk AssessmentConcerns About Risk Assessment

Asthma induction and asthma Asthma induction and asthma exacerbation are not well characterized in exacerbation are not well characterized in terms of dose-response.terms of dose-response. Comment: Work in progress--may be Comment: Work in progress--may be

possible in the future for some chemicals.possible in the future for some chemicals.

Advantages of Risk AssessmentAdvantages of Risk Assessment

Risk assessment provides a useful tool Risk assessment provides a useful tool that incorporates scientific information and that incorporates scientific information and serves as a yardstick for comparison. serves as a yardstick for comparison.

Risk assessment can be used to compare Risk assessment can be used to compare the risks between chemicals as well as the risks between chemicals as well as between different facilities and to inform between different facilities and to inform risk management decisions.risk management decisions.

Advantages of Risk AssessmentAdvantages of Risk Assessment

Risk assessment incorporates health Risk assessment incorporates health conservative assumptions.conservative assumptions.

It is much more defensible than not It is much more defensible than not considering issues of chemical toxicity and considering issues of chemical toxicity and exposure in decision-making.exposure in decision-making.

For More InformationFor More InformationAir Toxics "Hot Spots" Program Air Toxics "Hot Spots" Program

Risk Assessment GuidelinesRisk Assessment Guidelines Parts I, II, III & IV Technical Support Parts I, II, III & IV Technical Support

Documents Documents And the overview: Air Toxics Hot Spots And the overview: Air Toxics Hot Spots

Program Guidance Manual for Preparation Program Guidance Manual for Preparation of Health Risk Assessments. of Health Risk Assessments.

All at: All at: http://www.oehha.ca.gov/air/hot_spots/indhttp://www.oehha.ca.gov/air/hot_spots/index.htmlex.html