Timing of exposure assessment in relation to exposure occurrence:  Historical or retrospective: i.e., exposure reconstruction; an attempt to identify exposures occurring over a person’s past. - Example: reconstructing lifetime exposure to ionizing radiation for purposes of estimating cancer risk  Current: Advantage of being able to monitor environment and obtain relevant information. - Example: measure of current workplace exposure to lead to assess regulatory compliance  Prospective: for future risk. Generally based on scenarios describing, in the future, emission sources and exposure scenarios. - Example: estimating exposures to a population likely to be associated with a proposed waste incinerator

Timing Determines Exposure Assessment Methods  Retrospective: Approach is dependent on quality/quantity of relevant past direct measurements, but almost always relies heavily on modeling  Current: Multiple approaches to assessment likely to be available  Future: Necessarily involves modeling as exposures of interest have not yet occurred

Exposure Assessment Methods  Monitor general environment  Monitor microenvironments  Personal exposure monitoring  Questionnaires  Biological monitoring  Modeling Many approaches to exposure assessment --> Current Exposure Retrospective Exposure Exposure Analysis Approaches Direct MethodsIndirect Methods Personal monitoring Biological Markers Environmental Monitoring Questionnaires & Diaries Future (Prospective) Exposures Exposure scenario development Exposure models General environment Micro- environments

Exposure Assessment Methods: Hierarchy of Exposure Data or Surrogates (Indicators)  Biomarkers, biological monitoring (exposure, effect, susceptibility)  Personal measurements (personal, microenvironment)  Area or ambient monitoring in workplace, home, and outdoors  Surrogate of exposure (e.g., drinking water use)  Distance from industrial site and duration of residence  Residence or employment by proximity to industrial site  Residence or employment in geographic area (county) with site MOST ACCURATE LEAST ACCURATE

Equip individuals with sampling systems to:  Sample air in the breathing zone of individuals during normal daily activities  Can also sample food, water, etc. Personal Monitoring

Breathing-zone samples belt-mounted, battery-powered pump flexible tubing sampler on lapel –adsorbent tube (gas, vapor) –membrane filter (aerosols) Personal Exposure Monitoring

Microenvironmental Monitoring Measure microenvironments within which people spend time by:  Pollutant concentrations separately in each microenvironment  Time-activity, e.g., person- hours involve in a particular microenvironment  Weighting pollution measurements by time- activity.  Can include ambient monitoring

Exposed populations Individual Population activities diet lifestyle age gender genetics pre-existing illnesses home, work/school, leisure activities, transportation population density & geographic distribution exposuressusceptibility health effect Microenvironmental exposures

Example of NO 2 monitoring over day Sexton and Ryan (1989)

Exposure Assessment Methods

Biological Monitoring  sample urine, blood, expired breath, sputum, skin, hair, etc.  incorporates all exposure pathways, advantage especially for dermal contact which is problematic  doesn’t indicate pathway, disadvantage for management Kinds of biological markers ---> (Committee on Biological Markers, 1987)

Types of Biological Measurements  Chemical Dose - measure chemical, metabolites, or reaction products (indicating absorbed dose) e.g. solvent vapors - exhaled breath metals - blood, urine, hair metabolites (e.g., solvents) - blood, urine carboxyhemoglobin (CO) alkylated hemoglobin (ETO)  Biological Effect - measure alteration in biological function (indicating target dose) e.g. methemoglobin (aromatic amines & nitro compds effect) chlorinesterase inhibition (O.P. pesticides effect) ALA in urine (Pb effect),  -aminolevulinic acid dehydratase (ALAD) activity in blood (Pb effect) chromosome aberrations (mutagenic effect) SCE - sister chromatid exchange (mutagenic effect)

Advantages of Biological Monitoring (as compared to exposure measures only)  Reflects input from all routes under all situations –inhalation, dermal absorption, ingestion, non-occupational exposures (e.g. hobbies, etc.)  Accounts for individual differences –susceptibility, metabolism, body build, fitness, health status, personal hygiene, diet, obesity, work habits, exposure variability, co-exposures  Potentially allows measurement or inference of effective dose at target site  Potentially allows increasingly sensitive measure of impending adverse health effects  Potentially allows for more accurate correlations with clinical and epidemiological outcomes

Biological Monitoring  Disadvantages: doesn’t indicate pathway, a disadvantage for management  Four criteria for appropriate biological markers (Fiserova- Bergerova, 1995): Sensitive, i.e., measurable at occupational/environmental exposure levels and specific, i.e., not measurable after exposure to other chemicals. Eliminate false positives and chemical overlap. Acceptable levels of variability. Many factors cause variability including physiological and health status of the worker (age, gender, body weight, medication, disease status, pregnancy), noise (analytical errors). Ease of collection, i.e., should be measured in a biological media that is easily collected. Related to potential adverse health effects. These criteria are often very difficult to meet in practice.

Toxicokinetics  Used to describe the rates of uptake, distribution, metabolism and elimination of a chemical or metabolite in body fluids, tissues, organs, etc.  Methods used are similar to those used to study the action of drugs on the body (pharmacokinetics)  Most sophisticated models incorporate known information about physiologic processes – thus known as physiologically-based pharmacokinetic (PBPK) models

Toxicokinetic Modeling  Body is divided into “compartments” –simple models: 1 compartment –complex models: > 5 compartments  Assignment of tissues, organs to different compartments is based on: –perfusion level (amount of blood flow) –metabolic activity –solubility of chemical (partition coefficient)

Physiologically Based Pharmacokinetic (PBPK) Models Used to estimate distribution, metabolism, and excretion of substance: each arrow in the diagram has a separate rate constant which may need estimation!

Predicting Body Burden  Definition of body burden: The amount (mg) of a chemical, or its metabolite(s) present in the body at a given time  Toxicokinetic models used to determine amount of chemical (burden) present over time.  Consider a single-compartment model that follows 1st order kinetics X (t) C (t) Kk the change in burden, X, with time is: dX = KC - kX dt Burden X Time start exposure end exposure Equilibrium: KC = kx

Biological Half-Life (t 1/2 )  Consider elimination kinetics (post exposure) dX = - kX dt X(t) = X (o) e -kt  Biological half-life is the time needed to reduce burden to one-half initial value i.e. X(t) = (1/2) X (o) t 1/2 = ln2 = 0.69 k k  So, for small k, we have long t 1/2, and for large k we have a short t 1/2