Fig. 3

Depiction of US construct for deriving oral reference dose (RfD) and inhalation reference concentration (RfC)

RfD and RfC defined as exposure estimates that are “likely to be without an appreciable risk of deleterious effects during a lifetime” for non-cancer endpoints in the human population (including susceptible subgroups), when using experimental animal data. The RfD or RfC is derived from an experimental animal point of departure (POD), such as the statistical lower limit on a benchmark dose (BMDL) that is associated with a pre-determined change in response. Adjustment factors (AFs) to account for inter-species (experimental animal-to-human) differences and intra-species (healthy humans to susceptible subgroups) variability are then applied to the experimental animal POD. The POD is divided by the animal-to-human AF (AFA) to extrapolate from animals to humans and by the human variability AF (AFH) to account for within-human population variability [73]