Endocrine active substances and dose response for individuals and
populations
H. A. Barton
USEPA Office of Research and Development, National
Health and Environmental, Research Laboratory, Experimental Toxicology
Division, B143-01, Research Triangle Park, NC 27711, USA
Abstract: Dose-response characteristics for endocrine disruption
have been major focuses in efforts to understand potential impacts on
human and ecological health. Issues include assumptions of thresholds
for developmental effects, effects at low doses with nonmonotonic (e.g.,
"U-shaped") behaviors, population vs. individual responses, and background
exposures (e.g., dietary phytoestrogens). Dose-response analysis presents
a challenge because it is multidisciplinary, involving biologists and
mathematicians. Statistical analyses can be valuable for evaluating
issues such as the reproducibility of data as illustrated for contradictory
findings on low-dose effects. Mechanistically based modeling provides
insights into how perturbations of biological systems by endocrine active
substances can create different dose-response behaviors. These analyses
have demonstrated that higher order behaviors resulting from the interaction
of component parts may appear highly nonlinear, thresholded, low-dose
linear, or nonmonotonic, or exhibit hysteresis. Some effects need to
be evaluated as population impacts. For example, alterations in male:female
ratio may be important at the population level even though not adverse
for the individual. Descriptions of the contributions of background
exposures to dose-response behaviors are essential. The challenge for
improving dose-response analyses is to better understand how system
characteristics create different dose-response behaviors. Such generalizations
could then provide useful guidance for developing risk assessment approaches.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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