The estimated GSTT1 activity for this sensitive subpopulation was then used with the cancer risk per internal dose
obtained from modeling the animal cancer data to estimate the human cancer risk.
In the present study, we observed that perinatal exposure to human-relevant internal doses
of BPA--in the absence of additional exposure to chemical carcinogens--was associated with the induction of malignant mammary gland tumors and other lesions in adult female rats.
are the amounts/concentrations of environmental chemicals or their metabolites at the target site(s) of interaction with biological molecules, and are related to external doses by pharmacokinetic (PK) processes.
Thus, sulfation of BPA in neonates does not guarantee negligible internal dose
as assumed by the EFSA.
Exposure science provides the linkages between what is present in the environment and the internal dose
that individuals and populations receive.
The conclusions were documented in a seminal paper published in the October 1987 issue of EHP, which described the four basic biomarker groupings still in use today: exposure biomarkers (which include markers of external exposure and of internal dose
); biomarkers of biologically effective dose; effect biomarkers (which include markers of health impairment or recognized disease, early disease precursors, or peripheral events that predict health impairment); and susceptibility biomarkers (which include intrinsic genetic or other characteristics or preexisting diseases that result in an increase in internal dose
, biologically effective dose, or target tissue response).
With knowledge of the toxicokinetics, the internal dose
can then be estimated by measuring the level of a chemical, its metabolite, or its reaction product (a chemical adduct) in a biological medium.
This internal dose
can be directly eliminated (usually a minor route); distributed within the body to other organs including the target organ(s); metabolized and eliminated (usually in urine); metabolized and distributed within the body to other organs including the target organ; or some combination of these (Needham et al.
Although more research is needed to understand fully the complex relationship between external hazard concentrations, internal dose
, and health effects, biomonitoring data are an important component for comprehensive environmental public health surveillance.
The progression from exposure to disease is typically expressed as a continuum of environmental exposure [right arrow], internal dose
[right arrow] biologically effective dose [right arrow] early biologic effect [right arrow] altered structure and function [right arrow] and finally clinical disease.
Yet the ever-increasing data from human biomonitoring and epidemiological studies suggests otherwise: Low internal doses
of endocrine disruptors found in typical human populations have been linked to obesity (Carwile and Michels 2011), infertility (Meeker and Stapleton 2010), neurobehavioral disorders (Swan et al.
1181) discuss the role of exposure science in a fully integrated system for risk assessment and chemical prioritization, including its use to study relations between environmental exposures and internal doses
, identify susceptible populations, estimate risks associated with multiple exposures and exposures over time, and compare toxicity test doses with human exposures.