PRINCIPLES OF TOXICOLOGY

18.4 DOSE–RESPONSE ASSESSMENT 453
Figure 18.4 Derivation of the benchmark dose. Dose–response data for the toxic effect of concern are fit to
a mathematical model, depicted by the solid line. This model is used to determine the effective dose (ED)
corresponding to a predetermined benchmark response (BMR) (e.g., 10% of the animals responding). Statistical
treatment of the data can be used to derive the lower confidence limit estimate of the ED, termed the LED (see
dashed line). Either the ED or LED may be used to represent the benchmark dose (BMD), although the more
conservative LED is typically used for regulatory purposes. [Adapted from USEPA (1995).]
Interpretation of the HQ is relatively straightforward if the value is less than one. This means that the
estimated exposure is less than the SHD, and no adverse effects would be expected under these
circumstances. Interpretation of HQ values greater than one is more complicated. A value greater than
one indicates that the estimated exposure exceeds the SHD, but recall that the SHD includes a number
of uncertainty factors that impart a substantial margin of safety. Therefore, exposures that exceed the
SHD, but lie well within this margin of safety, may warrant further analysis but are unlikely to produce
adverse health effects.
Dose–response relationships can vary from one route of exposure to another. A safe dose for
inhalation of a chemical may be different from a safe dose for its ingestion, for example. As a result,
a given chemical may have different SHDs for different routes of exposure. Since individuals are often
exposed to a chemical by more than one route, separate route-specific HQ values are calculated. For
example, the dose estimated to be received by inhalation would be divided by the SHD for inhalation
to calculate a HQ for inhalation, while the estimated dose received from dermal contact would be