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Body or Tissue Burden Some Toxicants With Very Slow Elimination Half-Life Estimates Person-Specific Factors Affecting Uptake, Distribution, Metabolism, Elimination Physical stress exercise uptake increases blood chemistry increases/decreases excretion rate increases (e.g. Cr: 5 x increase with exercise) Diet high fat increase in blood solubility for organic solvents Health status disease liver function kidney function lung function Smoking source of increase in Pb, Ni, Cr, Cd increase in CO, CN- Alcohol ---- affects metabolism of other solvents by competing for metabolic enzymes Dose associated with exposure to biological agents • Exposures are usually of the ‘oneshot’ (acute) variety (as opposed to ‘chronic’): for example:– ingesting infected food or water – inhaling organisms suddenly present in ambient or workplace air – bite from a malaria-infected mosquito Current hot topics • blood-borne pathogens • drug-resistant TB • ‘bioterrorism’ ‘Yardstick’ for dose of infectious agents • Infectious dose (ID) – number of microorganisms (in the exposure) needed to initiate infection in the exposed subject. Factors To Consider • Viability and virulence of biological agent? • Host susceptibility? • Aerosolization? Example: Acute Exposure To A Biological Agent (e.g., by inhalation of M.Tuberculosis) (proximity to infected person, person coughs, bacteria released into the air inhaled by subject) EXPOSURE TO RISK OF TUBERCULOSIS INSTANTANTEOUS DOSE RAPID BIOLOGICAL RESPONSE (e.g., cellular changes) DISEASE T I M E Some Typical Numbers Disease Route ID Anthrax Inhalation 1,300 Q-fever Inhalation 10 TB Inhalation 10 Scenario for estimating risk of tb infection (rough!) • • • • • • • TB-infected person on aircraft Cabin volume, V m3 Ventilation air changes per hour, N hr-1 Person coughs X times per hour Release n organisms per cough Breathing rates of each passenger, R L/min Infectious dose, I organisms • Can we estimate risk of infection? Back of the envelope . . • • • • • • Total air volume = NV m3/hr Total organisms released = nX #/hr Average concentration = nX/NV #/m3 Breathing rate = R x 10-3 x 60 m3/hr Dose rate = (nX/NV)(Rx10-3x60) #/hr Total dose = (nX/NV)(Rx10-3x60).t organisms • Probability of infection for each passenger = nXRt PIpersonal ≡ NVI 0.06 Rough estimate . . . N = 10 hr -1, V = 1000 m3, X = 1 hr -1, n = 100 #/cough, R = 7 L/min, t = 7 hr, I = 10 # • For each individual on the plane, risk of infection is PIpersonal = 3 x 10-3 • Risk that someone of the plane will be infected (200 passengers) is PIanyone = 0.6 !!!!! Some Common Options for Environmental Exposure Assessment • Direct Measurement or Observation of Individuals or their Environment – Measurements outside front door or in home (Residential Radon) – Personal dosimetry (Personal monitors for ELF-EMF worn for 24 hours) – Proximity to toxic waste dump, industrial source, power lines • Biomonitoring – Measurement of organochlorines in blood or tissue Use of Routinely Collected Environmental Monitoring Data • Assigning values to study participants or populations – Mean levels for city applied to all residents – Mean levels from closest monitoring station – Mean value based on spatial modeling • Monitoring equipment and analysis • Years of availability • Averaging time Advantages of Geographic Information Systems (GIS) • A universal coding scheme for geographic based information • A means to integrate data from multiple sources • More precise mapping and imaging Using GIS for Wetlands Vulnerability Exposure to Air Pollution in Stockholm* • Postal questionnaire: all residences for 1+ years since 1955 (follow-up 1990-1995) – 10,800 addresses geocoded • Dispersion modeling – traffic (traffic on roads with >1000 vehicles/24 hrs, estimated to be 90% of total traffic emissions) – 500 point sources (emissions from industries, power plants, and ferries) – Areas sources related to population density & commercial uses * Bellander et al. Using Geographic Information systems to Assess Individual Historical Exposure to Air Pollution from Traffic and House Heating in Stockholm. Env Health Persp 2002;109:633-639. Air Pollution Modeling Gaussian Plume Model: Plume profiles under steady-state conditions may appear to have Gaussian distribution when averaged over time and space. Basic formulation asumes: steady state, averaged concentrations (1 hour) constant winds vertical and crosswind distributions are known & Gaussian negligible mass diffusion in x direction conservative pollutants (no transformation) no deposition and gravitational settling Determinants of Exposure Modeling: Indoor Air Pollution* • 60 homes, 24 hour samples for smoke, SO2, at least 7 successive days/home • 800 paired indoor/outdoor • Multiple regression, dependent: indoor levels • Determinants of exposure: – – – – Year of construction Type of heating Smoking habits Outdoor levels * Biersteker et al. Indoor Air Pollution in Rotterdam Homes. Int J Air Water Poll 1965;9:343-350.