PRINCIPLES OF TOXICOLOGY - Biology East Borneo

446 RISK ASSESSMENTchemical poses no risk. Conversely, excessive exposure to minimally hazardous chemicals may posean unacceptable risk. Therefore, risk assessment requires that toxicity and exposure assessments becoupled. Initially, exposure assessments should identify all potential exposure pathways and assesstheir completeness, after which the quantification of exposure via each relevant pathway should bedetermined.There are two basic methods for quantifying exposure: exposure measurement and exposuremodeling. Measurement results in the most accurate and realistic exposure data, but fully characterizingvariable exposures that might occur to multiple receptors via multiple pathways for an extended periodof time is seldom feasible. In general, the measurement of occupational exposure is easier thanenvironmental exposure, since the former usually occurs in a confined facility whereas the latterinvolves more complex time–activity patterns. Also, occupational exposure limits are typically basedon 8-h time-weighted averages and 15-min short-term exposure limits, making monitoring forcompliance purposes manageable from a time standpoint. Examples of personal exposure measuresinclude analyzing a person’s intake of food and water and the contaminants therein, collecting andanalyzing a urine sample at the end of a workshift, and measuring airborne exposure with a portablesampling device suspended in a person’s breathing zone. Where environmental exposure to a largepopulation is at issue, personal exposure monitoring is not a realistic approach. Rather, environmentalmedia suspected of being contaminated are sampled and population-based assumptions about intakerates are made. Frequently, personal questionnaires and time–activity logs are helpful in makingaccurate exposure estimates within a large population.In those cases where monitoring data are unavailable or inadequate for exposure assessment, modelsare used to simulate the behavior of chemicals and predict their concentrations in the environment.Hundreds of such exposure models exist, including atmospheric models, surface-water models,groundwater models, and food-chain models. All of these models are limited by uncertainty in the datainput, as well as uncertainty as to the predictive capability of a generic model for a specific exposurescenario. In recognition of this uncertainty, models used for regulatory purposes tend to provide liberalestimates of exposure that may overstate risk. Whenever models are used, an attempt should alwaysbe made to collect site- or situation-specific data for the purpose of model validation. Despite theirlimitations, exposure models are of value in that they can make predictions for an unlimited numberof exposure scenarios and predict past and future exposures. Exposure measurement, on the other hand,is limited to the present.Exposure or concentration is often expressed in units of µg/m 3 (air), µg/L (water), or µg/cm 2 (skin).Air and water concentrations are also frequently reported in parts per million (ppm) or parts per billion(ppb), units that reflect the weight or volume of chemical per unit volume of the carrier medium. Forsome chemicals, risk can be directly calculated from these concentration terms using unit risk factorsthat are expressed as risk per µg/L water or risk per µg/m 3 air. In such cases, risk is simply the productof the chemical concentration and the unit risk factor. A word of caution is in order, however. Sinceunit risks are based on exposure factors typical of an average adult (e.g., 70 kg body weight,consumption of 2 L/day water, breathing rate of 20 m 3 /day air), they must be adjusted accordinglywhen used to calculate the risk to receptors having different exposure factor values (e.g., children).Such adjustment is necessary since exposure factor values determine dose, which in turn determinesthe nature of the toxic response. In other words, exposure of an adult and child to the same concentrationof a chemical is likely to result in different doses that may translate into different toxic responses.Exposure or concentration data can also be directly compared to many occupational [e.g., OSHApermissible exposure limits (PELs), and American Conference of Governmental Industrial Hygienists(ACGIH) threshold limit values (TLVs)] and environmental [USEPA maximum contaminant levels(MCLs), national ambient air-quality standards, and reference concentrations (RfCs)] exposurestandards that have risk considerations inherent in their derivation.While some exposure to a hazardous chemical is required in order to have risk, it is dose that relatesmore closely to the toxic response. Dose, often expressed in units of mg/kg⋅day, is the amount of chemicalthat is either absorbed, or available to be absorbed, into the body where it can interact with the target tissue(liver, thyroid, red blood cells, etc.). Knowledge of the exposure or concentration of a chemical is essential