Although it has been proposed that BBDR models can eventually be used to quantitatively link biochemical and cellular responses to apical effects (Conolly 2009; Rhomberg 2009), as discussed in the next section, it appears that it will not be possible to develop such models from TP testing data in the foreseeable future.
BBDR models describe biological processes at the cellular and molecular level to link external exposure to an adverse apical response.
BBDR models are predictive models that describe biological processes at the cellular and molecular level to link external exposure to an adverse apical response.
Difficulties inherent in BBDR models limit the models' ability to provide reliable estimates of low-dose risk in humans.
BBDR modeling has the same problems for estimating low-dose risk as empirical modeling of apical responses.
It is less well understood that these exact same difficulties occur with BBDR models.
To link exposure with risk, a BBDR model must incorporate at least one biologic variable that is dose related.
BBDR modeling of low-dose effects is greatly complicated if the toxicant affects multiple intermediate steps in the disease process.
These problems are well illustrated by the experiences with BBDR models to date.
Many of the BBDR modeling efforts to date do not incorporate any biological data on one or more key intermediate variables.
Perhaps the most ambitious attempt to date at BBDR modeling is the model for cancer risk in the human respiratory tract from formaldehyde-induced nasal cancers observed in the F344 rat (Conolly et al.
Much of the enthusiasm for use of BBDR modeling in estimating low-dose risks may result from a general aversion to the default methods contained in U.