Exposure-response characterization

Risks to human health and the environment will vary considerably depending upon the type and extent of exposure. Responsible authorities are strongly encouraged to characterize risk on the basis of locally measured or predicted exposure scenarios. To assist the reader, examples of exposure estimation and risk characterization are provided in CICADs, whenever possible. These examples cannot be considered as representing all... 

Dose (exposure)-response relationship Characterization of the relationship between administered dose or exposure and the biological change in organisms. It may be expressed as the severity of an effect in one organism (or part of an organism) or as the proportion of a population exposed to a chemical that shows a specific reaction. 

Characterization of Dose-Response Estimates. Characterization of the estimated dose-response relationship involves a presentation of (1) the dose-response relationship per se and (2) a framework to help judge the significance of the relationship. Dose-response characterization includes an evaluation of exposure mechanisms during data acquisition, as well as how the dose-response relationship was established. If the dose-response relationship is linear at... 

Newhook, R., Meek, M.E., and Walker, M., Carbon disulfide hazard characterization and exposure-response analysis, Environ. Carcinog. Ecotoxicol. Rev., C19, 125-160, 2001. 

Where effects are known to be dependent on pulsed exposures, and the temporal nature of the exposures is modeled or measured, the exposures can be characterized using a tool such as the Risk Assessment Tool to Evaluate Duration and Recovery (RADAR), developed as part of the efforts of ECOFR AM (ECOFRAM1999 Reinert et al. 2002). This tool provides information on pulse magnitude, duration, and interpulse interval, which is particularly useful for assessing likely effects on classes of organisms with known recovery times and time-exposure responses. 

Re-exposure to the relevant hapten triggers the same cytokine responses that occur following induction and elicits a response characterized by rapid recruitment and activation of specific T cells at the site of hapten challenge (Figure 32.10). 

Direct irritation may thus be dehned as an adverse effect of chemicals directly applied to the skin that does not involve prior sensitization and thus initiation by an immune mechanism. Irritation is usually assessed by a local inflammatory response characterized by erythema (redness) and/or edema (swelling). Other responses may be present that do not elicit inflammation such as an increase in skin thickness. Irritant reactions may be classified as acute, cumulative, traumatic, or pustular. However, two classifications are generally used by toxicologists. Acute irritation is a local response of the skin usually caused by a single agent that induces a reversible inflammatory response. Cumulative irritation occurs after repeated exposures to the same compound and is the most common type of irritant dermatitis. 

Exposure assessments may be conducted for one of four purposes hazard evaluation leading to appropriate control efforts, monitoring to ensure compliance with workplace standards, dose-response characterization within the context of epidemiological studies, and estimation of dose or uptake for risk assessments. Assessment strategies and measurement techniques will differ depending on the purpose at hand. 

CHARACTERIZING DOSE AND RISK IN A CUMULATIVE ASSESSMENT 277 CASE STUDY 280 Case Study Defining Risk 280 Case Study The Dose-Response Relationship 280 Case Study Using the Margin of Exposure to Characterize the Risk 281 Case Study Benchmark Doses 282 Case Study Margins of Exposure 284... 

Many PK/PD models have been developed to characterize the exposure-response relationship for a variety of classes of drugs. In the following section we provide a brief discussion on some simple direct effect models that assume a rapid equilibrium between plasma... 

Hughes K, Meek ME, Walker M, and Beauchamp R (2003) 1,3-Butadiene Exposure estimation, hazard characterization, and exposure-response analysis. Journal of Toxicology and Environmental Health. Part B, Critical Reviews 6(1) 55-83. 

---