Exposure-Duration Relationships: The Risk Assessment Process for Health Effects Other Than Cancer

Abstract

The development of the risk assessment process over the past 10 years not only has provided us with a framework to carry out an important regulatory function, but also has aided in the identification of major gaps in our knowledge and the scientific database. One of those gaps is the influence of the duration of exposure on the toxicity of an agent. Currently, approaches to estimating short-duration exposure limits are only generally defined, assuming a constant relationship between the level of an exposure and its duration with respect to the response that can be expected. Within developmental toxicology, even this type of exposure duration adjustment is generally not carried out, the risk assessment being based on the overall daily exposure, regardless of the actual timing, duration, or frequency of exposure or the physicochemical properties of the agent. This article summarizes several current approaches to estimating short-duration exposure limits and outlines preliminary model development that may be useful in better defining the influence of exposure duration on toxicity. The focus is on developmental toxicity, but most of the concepts should be generally applicable to other noncancer health endpoints.