nuatrc/tceq air toxics workshop october 2005. air toxics air toxics: what we know, what we don’t...
DESCRIPTION
Questions: –1) Do better exposure estimates yield stronger associations with health effects ? –2) What is the appropriate proportion of attention that should be given to chronic and acute outcomes. –3) Do mortality, cancer, exacerbation of asthma, and other respiratory and cardiovascular diseases correlate with exposure ?TRANSCRIPT
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NUATRC/TCEQ Air Toxics Workshop
October 2005
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Air Toxics
Air Toxics: What We Know, What we Don’t Know, and What We Need to Know
Human Health Effects – Chronic
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Human Health Effects – Chronic
• Questions:
– 1) Do better exposure estimates yield stronger associations with health effects ?
– 2) What is the appropriate proportion of attention that should be given to chronic and acute outcomes.
– 3) Do mortality, cancer, exacerbation of asthma, and other respiratory and cardiovascular diseases correlate with exposure ?
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Perspectives
• Importance to chemical industry – Responsible Care®
• Chemical hazards versus chemical risks• Approaches• Opportunities
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Chemical industry:Responsible Care®
• A global, voluntary initiative to improve the environment, improve and protect the health and safety of our employees and community members.
• Responsible Care is more than a set of principles and declarations. It is implementing world-class management systems, verified through independent auditors; tracking performance through established environment, health, safety and security measures; and extending these best practices to business partners through the industry supply chain.
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Chemical hazards versus chemical risks
Elements to risk assessment (Source NAS, 1983)
Hazard identificationHazard evaluationExposure assessmentRisk characterization
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Chemical hazards versus chemical risks
Elements to risk assessment (Source NAS, 1983)
Hazard identificationHazard evaluationExposure assessmentRisk characterization
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Getting People ExposedGetting People Exposed – Fate and transport models:
Source: Mel Andersen, CIIT Centers for Health Research
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Public Health Paradigm
SOURCE / STRESSOR
FORMATION
TRANSPORT/ TRANSFORMATIO
N
ENVIRONMENTAL CHARACTERIZATI
ON
EXPOSURE
EXPOSURE CHARACTERIZATI
ON
* Factors/criteria Example:•Temporal context- Constant or intermittent•Source(s)
*Factors/criteriaExamples:•Comparative toxicokinetics•Uncertainty•Short half-life
RISK CHARACTERIZATI
ON
DOSE
•Individual•Community•Population
EARLY BIOLOGICAL
EFFECT
ALTERED STRUCTURE FUNCTION
ADVERSE OUTCOME
*Factors/criteria * Factors/criteria
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Chemical hazards versus chemical risks
Elements to risk assessment (Source NAS, 1983)Hazard identification
Chronic human health effects: cancer, developmental, reproductive, neurotoxicity,respiratory toxicity,..
Hazard evaluationExposure assessmentRisk characterization
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Risk assessment
Source: US EPA
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Approaches to risk assessment• Europe (EU)
– Margin of Safety (MOS) • ACGIH TLVs® for worker protection
– ‘represent concentrations that nearly all workers may be repeatedly exposed, day after day, over a working lifetime, without adverse health effects’
– Note: NOT meant to be a legal standard• EPA
– Several factors for uncertainty – some with more scientific basis than others.
– Probabilistic cancer risk• Individual States
– Texas - TCEQ
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Approaches to risk assessment
• Approaches, assumptions, and values vary, sometimes significantly: – Europe – ACGIH TLVs® – EPA– Individual States
• WHY ???– Policy, including history– Uncertainty
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Dose Response AssessmentDose Response Assessment
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Opportunities
Best available science:
Dosimetry – for a given exposure in test animals and humans how do tissue doses vary between species
Tissue Response – for a specified tissue dose, how will the response vary between test animals and humans.
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What tools help us evaluate these What tools help us evaluate these relationships?relationships?
Pharmacokinetic Models – calculate the tissue dose of active forms of the toxic chemical for various doses, dose-routes, and animal species
Pharmacodynamics Models – calculate the degree of response for any level of tissue dose in different species
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Physiologically Based Pharmacokinetic (PBPK) ModelingPhysiologically Based Pharmacokinetic (PBPK) Modeling
Define Realistic Model
Collect NeededData
Refine Model Structure
Make Predictions
Metabolic ConstantsTissue SolubilityTissue Volumes
Blood and Air FlowsExperimental System
Model EquationsX
X
X
X
XX
X X
Tiss
ue C
once
ntra
tion
Time
You can be wrong!
Liver
Fat
Body
Lung
Air
Source: Mel Andersen, CIIT Centers for Health Research
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Models for Cellular ResponsesModels for Cellular Responses
Normal Epithelia
l Cell
Adaptive
State
StressedState
Pathology
Necrosis
Atrophy
MolecularBiochemicalHistologic
Physiological
DosimetryDosimetryInhaled Stressors
VentilationVentilation Tissue Phase ReactionsCl2 HOCl + HClCH2O HCOOH
Source: Mel Andersen, CIIT Centers for Health Research
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Computational, High Content Biology
• Biological models of cellular responses, using high content data collection (genomics), focusing on computational biology of target cell signaling modules and dose responses related to activation of circuits and specific cellular responses
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Source: US EPA ORD
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Human Health Effects – Chronic
• Questions:
– 1) Do better exposure estimates yield stronger associations with health effects ? Exposure estimates are an important element, but the public health paradigm requires an understanding of health effects, including (particularly) dose response.
– 2) What is the appropriate proportion of attention that should be given to chronic and acute outcomes. Chemical (nature of hazards) and situation (exposure) specific.
– 3) Do mortality, cancer, exacerbation of asthma, and other respiratory and cardiovascular diseases correlate with exposure ? Depends on dose
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Conclusions
• Air Toxics: Health Effects Chronic
– What We Know• High dose hazard identification• A sense of the uncertainty.
– What we Don’t Know• Certainty about uncertainty.
– What We Need to Know• Biologically based pharmacokinetic and pharmacodynamic
models.