Basic Course: Supplemental Topics

Toxicological Parameter for Noncancer Effects: RfD

The following equation is used for deriving noncancer human health AWQC (mg/L):

The noncancer toxicological parameter needed for this calculation is the Reference Dose (RfD) (mg/kg-day), which equals the Point of Departure (POD) divided by the Uncertainty Factor (UF). (Remember that, at present, all noncancer risk assessments assume that there are safe doses and that adverse effects from exposure exhibit a threshold.)

Key Point. In calculating the human health AWQC for a chemical based on an RfD, a relative source contribution factor is included in the equation. This is a factor that looks at the portion of the total exposure that results from drinking the water and/or eating the fish/shellfish from that water body.

There are several Points of Departure (PODs) that can be used in calculating an RfD:

• Benchmark Dose (BMD) and its lower-bound (BMDL). The BMD is a dose that produces a predetermined change in response rate of an adverse effect (called the benchmark response or BMR) compared to background. The BMDL is a statistical lower confidence limit on the dose at the BMD.
• No Observed Adverse Effect Level (NOAEL). The highest dose in a study or group of toxicological studies that has no associated adverse effect.
• Lowest Observed Adverse Effect Level (LOAEL). The lowest dose in a study or group of studies that shows an effect. The effect(s) observed at that dose is/are called the critical effect(s).

The study that identifies the NOAEL or LOAEL (the one used as the POD) is called the critical study. Most of the older RfDs on IRIS (pre-1997) were calculated using the NOAEL or LOAEL as the POD. Many of the more recent assessments use the BMDL as the POD. Independent of whether the BMDL, NOAEL, or LOAEL is used as the POD for an RfD, that value is divided by uncertainty factors that range from 1 to 3,000 and in some cases 10,000 for assessments completed before 1997.

Disclaimer:
For informational purposes only–Not official statements of EPA policy.