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Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***
Fisher, J., L. Shaung, K. Crofton, R. Zoeller, E. McLanahan, A. Lumen, AND M. Gilbert. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***. Presented at Society of Toxicology meeting, March 10 - 14, 2013.
This abstract will be presented at the Society of Toxicology meeting, March 10-14, 2013, San Antonio, TX
A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model parameters, were used as a technique to evaluate HPT axis adaptations to dietary iodide intake in euthyroid (4.1 -39 pg iodide/d) and iodide deficient (0.31 and 1.2 pg iodide Id) conditions. Iodide deficient conditions in both the dam and pup were described with increased blood flow to the thyroid gland, TSH-mediated increase in thyroidal uptake of iodide and binding of iodide in the thyroid gland (organification), and in general, reduced thyroid hormone production and metabolism. Alterations in thyroxine (T4) homeostasis were more apparent than for triodothyronine (T3). Model predicted average daily area-under-the-serum- concentration-curve (AUC, nM*day) values for T4 at steady-state in the dam and pup decreased by 14-15% for the 1.2 pg iodide /d iodide deficient diet and 42 to 52% for the 0.31 pg iodide /d iodide deficient diet. In rat pups that were iodide deficient during gestation and lactation, these decreases in serum T4 levels were associated with synaptic response suppression in the hippocampal region of the brain, while other measures of neurotoxicity were unaltered.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION