Table 1.

Components of adjustment, variability, and uncertainty in some typical uncertainty factors.

Uncertainty factor	Adjustment	Variability	Uncertainty	Comment
Correcting dose for body size	✓		✓	Oral dose in mg/day may be adjusted to mg/(kgα day), where the value of α may be chosen to be 1 or < 1; this value is assumed to hold generically, so there is no variability, but the value of α is uncertain. Generic adjustments have also been derived for inhalation exposures based on regional gas or particle dosimetry derived from respiratory tract geometry and airflow.
Interspecies toxicokinetic or toxicodynamic differences	(✓)a		✓	Assuming that the test animal and humans are (on the appropriate dose scale) equally sensitive, on average, to chemicals overall, no further adjustment is needed (i.e., the factor equals 1). However, species do differ in sensitivity from one chemical to another. This chemical-to-chemical variability translates into uncertainty about the appropriate factor for a single chemical.
Intraspecies		✓	✓	Some humans are expected to be more sensitive than others, but for a single chemical and effect, it is uncertain how many of them are more sensitive and by how much. Thus, there is variability, the size of which is uncertain.
Subchronic/chronic	✓		✓	On average, for chemicals overall, a given effect may be expected to occur at a lower dose with chronic exposure than with subchronic exposure (hence adjustment), but a single chemical may deviate to an uncertain degree.
Database	✓		✓	When one study type systematically results in lower PODs, then adjustment would be needed, while a single chemical may deviate to an uncertain degree.
aThe adjustment factor is assumed to be 1 in this case, so that it appears to be absent in the calculations.