RfDs

RfD stands for Reference Dose, a toxicological benchmark used to estimate a daily oral exposure to a chemical that is likely to be without appreciable risk of deleterious effects during a lifetime for humans, including sensitive subgroups. It is expressed in milligrams of chemical per kilogram of body weight per day (mg/kg-day) and typically refers to noncancer health effects.

RfDs are derived from toxicology data, usually selected from the study’s NOAEL (no observed adverse effect level) or, when NOAEL is unavailable, the LOAEL (lowest observed adverse effect level). Values are then divided by uncertainty factors to account for interspecies differences (animals to humans), intraspecies differences (human variability), and data gaps or other concerns. Commonly, these factors total around 30 to several hundred, depending on the chemical and data quality. In some risk assessments, additional factors may be applied to protect sensitive subpopulations.

RfDs are used in regulatory risk assessments to inform limits or guidelines for daily exposure from sources such as drinking water, food, consumer products, and ambient air. They are published in databases such as the U.S. Environmental Protection Agency’s IRIS, and are complemented by other agencies’ values, such as minimal risk levels provided by ATSDR. RfDs pertain to chronic exposure and do not address cancer risk; for carcinogens, risk is often characterized with different methods, such as linear or non-linear cancer slope factors.

Limitations include inherent uncertainties in extrapolating animal data to humans and variability among individuals; an RfD is a protective guideline rather than an exact threshold.