Process of an Agent from Environment to Human Body

There are two steps in the process of an agent entering the human body: contact (exposure), followed by actual entry crossing the boundary including an absorption (EPA, 1992). The absorption leads to the availability of an amount of the agent to target organs or cells within the body (internal dose) (WHO, 2000).

The process of an agent entering the body can be described in two types, intake and uptake (EPA, 1992). Intake is a process of physical moving an agent under study through an opening in the outer boundary (usually the mouth or nose), typically through inhalation, ingestion, or drinking (WHO, 2000). In most of cases, the agent is contained in an environmental medium (e.g., air, food, or water). To estimate the amount of the agent entering into the human body focuses on the amount of the carrier medium enters (EPA, 1992). During the intake, mass transfer occurs by bulk flow, and the amount of the agent itself crossing the boundary is described as an agent intake rate (Kathryn et al., EPA, 1992). The agent intake rate is the amount of an agent crossing the outer boundary per unit time, and is the product of the exposure concentration times the ingestion or inhalation rate (Aronson et al., 2000; Backer et al., 2005). Ingestion and inhalation rates are the amount of the carrier medium crossing the boundary per unit time, such as m³ air breathed/hour, kg food ingested/day, or liters of water consumed/day (WHO, 2000). Ingestion or inhalation rate is not constant over time (Baldauf et al., 2006; Bouvier et al., 2006).

The second process is uptake. Uptake is a process of absorption of the agent through the skin or other exposed tissue such as the eye (WHO, 2000). Although the agent is often contained in a carrier medium (e.g., air, water, and, and soil), the medium itself usually is not absorbed at the same rate as the agent (Hoppin et al., 2006). Therefore, estimates of the amount of the agent crossing the boundary cannot be made in the same way as for intake (EPA, 1992). Dermal absorption is an example of direct uptake by which an agent crosses the boundary from outside to inside the body (Hoppin et al., 2006). An agent uptake rate is the amount of the agent absorbed per unit time (Lioy PJ, 1990; Wallance LA, 1995). In this process, mass transfer occurs by diffusion, so uptake can depend on the concentrations gradient across the boundary, permeability of the barrier, and other factors (EPA, 1992). Agent uptake rates can be expressed as a function of the exposure concentration, permeability coefficient, and surface area exposed, or as a flux (Lioy, 1990). Table 1-1 summarizes concepts and dose terms for dermal, inhalation, and ingestion exposures (EPA, 1992).

Table 1-1: Summary of concepts and dose terms for dermal, inhalation, and ingestion exposures

Variables	Definitions	Typical units
Exposure	Contact with a chemical, biological, physical agent at the boundary of the human body over a specified time period	Dermal: water = (mg/L)·(hrs of contact) or Soil = (mg/kg)·(hrs of contact) Inhalation: Air = (ppm) ·(hrs of contact) or (µg/m3)·(days of contact) Ingestion: Water = (mg/L)·(min of contact), or (mg/kg)·(min of contact)
Potential dose	Amount of an agent deposited on a surface such as food ingested, air breathed, or soil applied to the skin	Dermal: Soil = (mg/kg)· (kg on skin) = mg in soil applied to skin Inhalation: Air = (µg/m3)·(m3 breathed/min) x (min exposed) = µg agent in air breathed Ingestion: Water = (mg/L)·(L consumed/day) x days exposed = mg ingested in water (also dose rate: mg/day)
Applied dose	Amount of an agent that is available to be absorbed in the absorption boundaries (e.g., skin, lungs gastrointestinal tract)	Dermal: Soil = (mg/kg)·(kg directly touching skin) x (% of agent in soil actually touching skin) = mg actually touching skin Inhalation: Air = (µg/m3) ·(m3 directly touching lung) x (% of agent actually touching lung) = mg actually touching lung barrier Ingestion: Food = (mg/kg)·(kg consumed/day) x (% of agent touching digestion tract) = mg actually touching digestion tract absorption barrier
Internal dose	The amount of an agent across body boundary through either physical or biological process	Dermal: Soil = mg absorbed through skin Inhalation: Air = mg absorbed through lung Ingestion: Food = mg absorbed through ingestion tract Dose rate = mg absorbed/day or mg/kg day)
Biologically effective dose	Amount of agent reaching tissue, organ, or cell	mg available to an organ or a cell Dose rate = mg/day
Note: ppm = parts per million Data source: Data source: U.S. EPA, 1992. Guidelines for Exposure Assessment.

Examples of Dose Calculation

Potential dose for intake processes

The general equation for potential dose for intake processes, e.g., inhalation and ingestion is the integration of the agent intake rate (concentration of the agent in the medium (C) times the intake rate of the medium IR) over time (WHO, 2000):

(Equation 1-1)

Internal dose for uptake processes

For absorption processes, there is a method generally in use for calculating internal dose. This method is commonly used for dermal absorption from a liquid where at least partial immersion occurs (WHO, 2000; EPA, 1992).

(Equation 1-2)

Where D_int is an internal dose, C(t) is the agent concentration, K_p is the permeability coefficient, and SA is the surface area exposed. The equation is similar to Equation 1-1 except that the agent uptake rate (C · K_p · SA) replaces the agent intake rate (C · IR).