Employing the calibrated [E.sub.max] model (Equation 1), we determined benchmark internal doses
for a 15% deficit in spatial memory function using peak CPF concentrations in the brain as the internal dose
metric (Table 3).
With regard to the child participants, it was interesting to observe that age was inversely related to internal dose
as measured in urine or toenails.
For evaluation of their use as exposure biomarkers (internal dose
), we compared these with previously measured concentrations of the elements in blood (erythrocyte fraction) and urine (Ahmed et al.
Such an interpretation would greatly restrict our ability to move from surface-level exposure measures to internal dose
, pharmacokinetics, and in vivo pathophysiology.
The PBPK model was then used to integrate the information on various physiological and metabolic distributions to predict distributions for several internal dose
metrics in the population as a whole as well as some population segments.
"We were measuring response to internal dose
and looking for preneoplastic lesions.
Applying this relationship to our internal dose
study, one may conclude that the pups from the BPA250 dams were lactationally exposed to 0.8 ug total BPA/kg BW/day, below the current U.S.
It is generally assumed that the undesirable effects of BPA are associated with plasma concentrations (internal dose
) rather than the administered BPA dose.
Figure 2 illustrates the distinct effects of different sources of variability on external dose, internal dose
, or biological response.
In a longitudinal cohort study of nonsmoking African-American and Dominican women in New York City (the Northern Manhattan Mothers and Newborns Study), the authors measured PAH exposure during pregnancy using personal air monitors and quantified benzo[a]pyrene DNA adducts and genomic DNA methylation in cord blood DNA among 164 participants, and they assessed PAH internal dose
using prenatal urinary metabolites in a subset of the women (n = 87).
Relationship between administered and internal dose
of BPA, and age-related changes in BPA pharmacokinetics.
Thus, although there is a clear need to test different routes of chemical exposure when assessing toxicity, it is equally important to focus on the internal dose
of the chemical in order to compare animals and people.