Abstract

Context: This study reviews factors in children, which alter their risk to inhalational exposures, and modify the inhalational risk assessment process. Factors identified in the literature distinguish children from adults when assessing risk of inhalational exposures. Such factors are determined based on children’s unique physiological, anatomical, and biochemical characteristics, which extend to include a unique inhalational dosimetry. Numerous methods have been developed to account for such factors in children. However, some factors are more inclusive than others are, and a comprehensive assessment of these factors is important to enhance risk analysis in children.
Objective: The aim was to identify factors in children that modify the four steps of risk assessment and assess the magnitude of uncertainty associated with these factors.
Methods: Authors did not follow a specific system for selecting articles from the literature. However, original and review articles were chosen based on their relevancy to the objectives of this paper. Five EPA documents and one WHO document were used to identify factors shown in Figure 1. EPA guidelines for inter and intra species differences and for inhalational dosimetry were used in calculating uncertainty associated with the identified factors.
Results: Figure 1 illustrates factors identified as influential in children’s inhalational risk assessment, with the elucidation of possible correlations that exist among these factors. Table 1 ranks factors in order of their importance and determination in two selected steps of risk assessment. Figure 2 evaluates uncertainty related to factors shown in Figure 1 based on criteria described in Methodology. Figure 3 demonstrates the inclusiveness of each of the methods used to assess risk in children.
Conclusion: Children’s risk assessment demands special considerations and the inclusion of factors specific to them because of their continuous developmental changes, which differentiate them from adults.

Key words: Inhalational risk assessment, pharmacokinetics, pharmacodynamics, physiologically based pharmacokinetic models, uncertainty factors