Harmonization Project Document No

The historical context of uncertainty estimation in exposure assessment can be traced to the convergence of developments in multiple disciplines. For example, Stanislaw Ulam and John von Neumann are typically credited with creation of the Monte Carlo method for simulation of random events in 1946 (see Metropolis Ulam, 1949 Eckhardt, 1987). However, a paper by Lord Kelvin in 1901 appears to apply concepts similar to Monte Carlo to a discussion of the Boltzmann equation, and there are other precedents (Kelvin, 1901). The modem incarnation of Monte Carlo was first used for prediction of neutron release during nuclear fission and has since been applied in a wide variety of disciplines. 

Decision-makers and stakeholders typically ask a variety of questions about exposure. These questions motivate both the structure of the exposure assessment and the need for uncertainty analysis in that assessment. They include the following  

To address these questions, an exposure assessment should begin with a definition of the assessment objective (section 2.2.1). From this follows the need to define and evaluate the conceptual exposure model (section 2.2.2). The goal of the conceptual model is to establish exposure links via exposure pathways to exposure routes and relative magnitude of uptake or intake by different exposure routes. These questions are discussed in more detail in section 5.4 with respect to interpretation of the results of a probabilistic exposure assessment. 

Exposure assessments provide important inputs to risk assessments and other health studies. Although the discussions here are broadly relevant to exposure assessments, our particular 

In conducting an exposure assessment, analysts are often challenged to address a number of technical questions, such as  

---

WHO/IPCS. 2005. Chemical-specific adjustment factors for interspecies differences and human variability Guidance document for use of data in dose/concentration-response assessment. Harmonization Project Document No. 2. http /whqlibdoc.who.int/publications/2005/9241546786 eng.pdf... 

WHO/IPCS. 2004. IPCS glossary of key exposure assessment terminology. In IPCS Risk Assessment Terminology. Harmonization Project Document No. 1. Geneva WHO. http //www.inchem.org/documents/sids/ sids/risk assess.pdf... 

---