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EPA-Expo-Box (A Toolbox for Exposure Assessors)

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Inhalation

Methods

When a contaminant is taken into the body via inhalation, the amount that gets into the body in a biologically available form is called the dose. There are a few different ways to measure dose (U.S. EPA, 1992):

  • Potential dose is the amount of contaminant inhaled (i.e., amount that gets in the mouth or nose), not all of which is actually absorbed.
  • Applied dose is the amount of contaminant at the absorption barrier (e.g., respiratory tract) that can be absorbed by the body.
  • Internal dose is the amount of contaminant that gets past the exchange boundary (lung) and into the blood, or the amount of the contaminant that can interact with organs and tissues to cause biological effects.
  • Biologically effective dose is the amount of contaminant that interacts with the internal target tissue or organ.
Illustration of Inhalation Route: Exposure and Dose
Illustration of Inhalation Route: Exposure and Dose (U.S. EPA, 1992)

The amount of chemical that is absorbed through the lung (i.e., the internal dose) may vary from the amount of the substance that is inhaled (i.e., the potential dose) based on the anatomy and physiology of the respiratory system and characteristics of the chemical. Assessors should be aware of how internal dose might vary from potential dose when evaluating potential risk.

Inhalation—A Complicating Factor

According to EPA’s Exposure Factors Handbook: 2011 Edition: “The Agency defines exposure as the chemical concentration at the boundary of the body (U.S. EPA, 1992). In the case of inhalation, the situation is complicated by the fact that oxygen exchange with carbon dioxide takes place in the distal portion of the lung. The anatomy and physiology of the respiratory system as well as the characteristics of the inhaled agent diminishes the pollutant concentration in inspired air (potential dose) such that the amount of a pollutant that actually enters the body through the upper respiratory tract (especially the nasal-pharyngeal and tracheo-bronchial regions) and lung (internal dose) is less than that measured at the boundary of the body.”

When using inhalation dose-response values (i.e., reference concentrations [RfCs] for evaluating noncancer effects or inhalation unit risk [IURs] for evaluating cancer effects) from the Integrated Risk Information System (IRIS) to characterize risk, it is not necessary to calculate the inhaled (i.e., applied) dose because the IRIS methodology accounts for inhalation rates in the development of “dose-response” relationships. Instead, only an air concentration is needed to evaluate health concerns. The methods used in developing noncancer inhalation dose-response values for IRIS are discussed in more detail in the U.S. EPA report entitled Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry (U.S. EPA, 1994).

The Superfund Program has also recently updated its approach for determining inhalation risk, eliminating the use of inhalation rates when evaluating exposure to air contaminants as described in Risk Assessment Guidance for Superfund (Part F, Supplemental Guidance for Inhalation Risk Assessment) (U.S. EPA, 2009). This updated methodology recommends that risk assessors use the concentration of the contaminant in air (Cair) as the exposure metric (e.g., mg/m3) instead of the intake of a contaminant in air based on inhalation rate and body weight (dose; e.g., mg/kg-day). Inhalation risk assessments may require that Cair be adjusted to represent exposure over various timeframes. The calculation to estimate an adjusted air concentration is different for noncarcinogens and carcinogens. For noncarcinogens, the concentration is adjusted based on the time over which exposure occurs (i.e., the exposure duration). For carcinogens, the concentration is averaged over the lifetime of the individual (see Calculations tab of this module).

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