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Def'n: exposure
Contact with a chemical, biological, or physical agent (sum total of exposure - integrated/aggregate/cumulative exposure via all routes of exposure) at the boundary of the body over a specified time period.
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Define boundaries of the body.
- 1. outer boundary (skin, openings into the body)
- 2. boundaries which agent must cross to be absorbed into the body resulting in internal dose (skin, lungs, GI tract)
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Define Exposure Route.
How a substance contacts body and results in internal dose (inhalation, ingestion, dermal penetration).
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What's exposure assessment?
Measures magnitude, frequency, duration, & route of exposure of animals, materials, ecological components to substances in the environment.
Describes size & nature of exposed population.
Determines sources, environmental transport & modification, & fate of pollutants & contaminants (and result of being exposed to contaminants).
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Type of contaminant agents.
Biological, physical, chemical
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Origin of contaminant agent.
Natural & synthetic
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What're the 3 main routes of exposure transport?
Inhalation, dermal, ingestion
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Define potential dose & applied dose.
Potential dose is amt of chemical that's ingested/inhaled/applied to skin, but not yet in body (?).
- Applied dose is subset of potential dose.
- - amt of chemical available at the absorption barrier (skin, lung, GI tract).
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Define internal dose.
Amt of chemical that's been absorbed & is available for interaction w/ biologically significant receptors.
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Define delivered dose.
Amt transported to an organ/tissue/fluid of interest.
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Define biologically effective dose.
Amt that reaches cells/sites/membranes where adverse effects occur.
The best for predicting adverse effects.
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Arrange the different dose markers in order of dosage effect.
Potential --> applied --> internal --> delivered --> biologically effective
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What's the unit for exposure?
exposure = concentration*period of time
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What's the eqn for dose?
dose = absorption rate * time
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What's the unit for concentration?
usually mg/m^3
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What's the unit for total dose and TWA dose?
- Total dose = mass / body wt
- TWA dose = mg / (kg*day)
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What's the difference btw. acute, chronic & subchronic exposure?
- Acute exposure: generally 1 contact w/ the chemical; usually < 1 day / short term.
- Chronic exposure: exposure takes place over substantial portion of lifetime
- Subchronic exposure: exposures of intermediate duration, e.g. usually in temp. job
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What're the exposure assessment methods (6)?
- - monitor general environment
- - monitor microenvironments
- - personal exposure monitoring
- - questionnaires
- - biological monitoring
- - modeling
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What's the hierarchy of exposure data/surrogates from exposure assessment methods?
- Most accurate
- - biomarkers, biological monitoring
- - personal measurements
- - area/ambient monitoring in workplace, home & outdoors
- - surrogate of exposure (e.g. drinking water use)
- - distance fm industrial site & duration of residence
- - residence/employment by proximity to industrial site
- residence/employment in geographic area w/ site
- Least Accurate
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Protective assessments
- - designed for initial investigations as screening tool, and for risk-based corrective actions.
- - general criterion is conservatism as it often estimates exposure to most-exposed individual (higher concentration)
- - use generic parameters
- - often criticized as overly conservative
- - often used in prospective risk assessments
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Predictive assessments
- - designed to assess actual exposure to pop'n for use in epid, dose-response studies- uses reasonable case scenario
- - requires demographic info
- - requires site-specific parameters
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Uncertainty VS vaiarbility
Uncertainty represents lack of knowledge abt factors affecting exposure/risk, and can lead to inaccurate/biased estimates.
Variability arises fm true heterogeneity across ppl/places/time, and can affect precision of estimates & degree which they can be generalized.
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What's probabilistic models?
It is uncertainty analysis, which accounts for uncertainty in select parameters evaluating the range & probability of plausible exposure levels.
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What's the eqn for intake or absorbed dose?
V*C*B
volume in L/day * concentration in ug/L * bioavailability
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What are the 4 exposure assessment applications?
- - Environmental & occupational epid
- - risk assessment
- - risk management
- - dx & tx of diseases
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odor assessment formula
X ppm = (Y mg/m3)(24.45) / (molecular weight)
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What does it require to assess inhalation exposure (3)?
- - specification/knowledge of target organ
- - mechanisms of toxicity
- - physical properties of contaminant
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How is required to assess inhalation exposure if target organ isn't respiratory tract?
absorbed dose (which is the quantity entering the bloodstream available for distribution to other body compartments)
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What's the eqn to estimate ADD (absorbed dose for inhalational exposure)?
ADD = (C*IR*D*B) / W
B isn't stable in calculation of inhalational exposure
- ADD = mg/kg*day
- C = ug/m^3
- IR = m^3/day
- D = day
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What does inhalation rate depend on?
Age, gender, wt, hlth status, level of physical activity
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In what situation is bioavailability assumed to be 100% for inhalation exposure?
when agents depositing in the respiratory exchange region (alveoli & respiratory bronchioles)
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What's the diff. between high & low water soluble chemicals?
Highly h20 soluble chemicals tend to give upper respiratory tract effects with good warning properties
Low h20 soluble chemicals tend to give deep lung/alveoli effects that have poor warning properties
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What're the 2 types of inhalational agents?
- 1. Gases & vapors: reach all regions of respiratory tract; absorption/toxicity depend on chemical properties
- 2. Aerosols: toxicity depends on chemical & physical properties
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What're the types of aerosols (7) and describe each?
dust: irregular solid produced fm disintegration of parent material by crushing, grinding, etc.
fiber: dust particle but with aspect ratio L/W > = 3
smoke: produced fm combustion of organic matter (spherical particles)
fume: produced fm condensation of vapor/gaseous combustion product (spherical particles), very small when produced, tend to agglomerate; e.g. fm welding, brazing
mist: liquid particle formed fm condensation/atomization
- fog: visible mist
- smog: smoke & fog; photochemical rxn products
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What're the 4 size descriptors for particle? What're they IMP for?
Most IMP
- Size - most IMP determinant of aerosol behavior
- Density
- Shape
- Diameter - IMP for descriptor, determined by microscope & aerodynamic
* particle size (aerodynamic diameter) critical in determining pattern of respiratory deposition that's IMP for regional toxic effects & systemic absorption
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What're the 2 particle size distributions?
Monodisperse: very rare; not in industrial processes; all particles 'same size'/narrow distribution; e.g. pollens, spores
Polydisperse: typical for industrial processes; range of sizes
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What can't Gaussian Distribution describe well?
Gaussian/normal distri. usually doesn't describe well distributions of aerosols generated fm industrial processes.
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What're the factors governing aerosol behavior?
- 1. Aerodynamics (respiratory tract deposition, design/operation of samplers)
- 2. Forces acting on aerosols (gravitational/sedimentational, inertial, diffusional, electrostatic, thermal)
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What're the 3 different respiratory tract regions?
NP, tracheobroncial, gas exchange region.
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Describe potential agents and their toxic effects in each of the 3 diff. respiratory tract regions.
- NP
- Agents: allergens, inorganic dust, salts, etc.
- Effects: Rhinitis, ulceration, nasal cancer
- TB:
- Agents: inorganic acids & bases, cotton dust, grain dust, allergens, etc.
- Effects: broncho constriction & bronchitis, bronchial carcinoma
- GER
- Agents: molds, etc.
- effects: pulmonary inflammation, pulmonary carcinoma, pulmonary fibrosis
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Define the diff btw gas & vapor.
Gas is in gaseous state when 25 degrees Celcius, 1 atm
Vapor is gas phase of a substance that's liquid or solid at 25 degrees Celcius, 1 atm
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What's the eqn. to est. maximum possible air concentration for pure liquid or solid with vapor pressure?
C max = vapor pressure / atmospheric pressure * 10^6
atmospheric pressure = 760 usually when it's rm temp.
- Assume:
- 1. closed system
- 2. saturation conditions
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What's the eqn to calculate bioavailability for inhalational exposure?
B = [(fraction remaining in lower respiratory tract) * (resp. tract absorption efficiency) + (fraction ultimately swallowed) * (GI tract absorption efficiency)]
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What's the eqn to calculate fraction remaining in lower resp. tract from part of the eqn to calculate bioavailability?
- fraction remaining in lower resp. tract
- = 1 * (alveolar fraction) + 0.5 * (bronchial fraction)
- = 1 * [(fraction of total particulate mass)*(alveolar deposition fraction)] + 0.5 * (fraction of total particulate mass)*(bronchial deposition fraction)]
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