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.
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)
Define Exposure Route.
How a substance contacts body and results in internal dose (inhalation, ingestion, dermal penetration).
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).
Type of contaminant agents.
Biological, physical, chemical
Origin of contaminant agent.
Natural & synthetic
What're the 3 main routes of exposure transport?
Inhalation, dermal, ingestion
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).
Define internal dose.
Amt of chemical that's been absorbed & is available for interaction w/ biologically significant receptors.
Define delivered dose.
Amt transported to an organ/tissue/fluid of interest.
Define biologically effective dose.
Amt that reaches cells/sites/membranes where adverse effects occur.
The best for predicting adverse effects.
Arrange the different dose markers in order of dosage effect.
Potential --> applied --> internal --> delivered --> biologically effective
What's the unit for exposure?
exposure = concentration*period of time
What's the eqn for dose?
dose = absorption rate * time
What's the unit for concentration?
What's the unit for total dose and TWA dose?
- Total dose = mass / body wt
- TWA dose = mg / (kg*day)
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
What're the exposure assessment methods (6)?
- - monitor general environment
- - monitor microenvironments
- - personal exposure monitoring
- - questionnaires
- - biological monitoring
- - modeling
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
- - 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
- - 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
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.
What's probabilistic models?
It is uncertainty analysis, which accounts for uncertainty in select parameters evaluating the range & probability of plausible exposure levels.
What's the eqn for intake or absorbed dose?
volume in L/day * concentration in ug/L * bioavailability
What are the 4 exposure assessment applications?
- - Environmental & occupational epid
- - risk assessment
- - risk management
- - dx & tx of diseases
odor assessment formula
X ppm = (Y mg/m3)(24.45) / (molecular weight)
What does it require to assess inhalation exposure (3)?
- - specification/knowledge of target organ
- - mechanisms of toxicity
- - physical properties of contaminant
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)
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
What does inhalation rate depend on?
Age, gender, wt, hlth status, level of physical activity
In what situation is bioavailability assumed to be 100% for inhalation exposure?
when agents depositing in the respiratory exchange region (alveoli & respiratory bronchioles)
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
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
What're the types of aerosols (7) and describe each?
: irregular solid produced fm disintegration of parent material by crushing, grinding, etc.
: dust particle but with aspect ratio L/W > = 3
: produced fm combustion of organic matter (spherical particles)
: produced fm condensation of vapor/gaseous combustion product (spherical particles), very small when produced, tend to agglomerate; e.g. fm welding, brazing
: liquid particle formed fm condensation/atomization
- fog: visible mist
- smog: smoke & fog; photochemical rxn products
What're the 4 size descriptors for particle? What're they IMP for?
- Size - most IMP determinant of aerosol behavior
- 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
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
What can't Gaussian Distribution describe well?
Gaussian/normal distri. usually doesn't describe well distributions of aerosols generated fm industrial processes.
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)
What're the 3 different respiratory tract regions?
NP, tracheobroncial, gas exchange region.
Describe potential agents and their toxic effects in each of the 3 diff. respiratory tract regions.
- Agents: allergens, inorganic dust, salts, etc.
- Effects: Rhinitis, ulceration, nasal cancer
- Agents: inorganic acids & bases, cotton dust, grain dust, allergens, etc.
- Effects: broncho constriction & bronchitis, bronchial carcinoma
- Agents: molds, etc.
- effects: pulmonary inflammation, pulmonary carcinoma, pulmonary fibrosis
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
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.
- 1. closed system
- 2. saturation conditions
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)]
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)]