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1.
Toxicol Appl Pharmacol ; 322: 9-14, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28263825

RESUMO

The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15µg/L, 20µg/L, or 24.5µg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198µg/kg/day). We determined that a daily intake of 0.45 to 0.50µg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25-0.3µg/kg/day. Assuming a drinking water intake rate of 0.033L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6-9.2µg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher.


Assuntos
Modelos Estatísticos , Percloratos/sangue , Percloratos/toxicidade , Terceiro Trimestre da Gravidez/sangue , Tiroxina/sangue , Poluentes Químicos da Água/sangue , Adulto , Água Potável/efeitos adversos , Água Potável/normas , Exposição Ambiental/efeitos adversos , Exposição Ambiental/normas , Feminino , Humanos , Percloratos/urina , Gravidez , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez/urina , Medição de Risco , Estados Unidos/epidemiologia , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/urina , Abastecimento de Água/normas
2.
Toxicol Appl Pharmacol ; 314: 24-38, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27818216

RESUMO

Previously, a deterministic biologically-based dose-response (BBDR) pregnancy model was developed to evaluate moderate thyroid axis disturbances with and without thyroid-active chemical exposure in a near-term pregnant woman and fetus. In the current study, the existing BBDR model was adapted to include a wider functional range of iodine nutrition, including more severe iodine deficiency conditions, and to incorporate empirically the effects of homeostatic mechanisms. The extended model was further developed into a population-based model and was constructed using a Monte Carlo-based probabilistic framework. In order to characterize total (T4) and free (fT4) thyroxine levels for a given iodine status at the population-level, the distribution of iodine intake for late-gestation pregnant women in the U.S was reconstructed using various reverse dosimetry methods and available biomonitoring data. The range of median (mean) iodine intake values resulting from three different methods of reverse dosimetry tested was 196.5-219.9µg of iodine/day (228.2-392.9µg of iodine/day). There was minimal variation in model-predicted maternal serum T4 and ft4 thyroxine levels from use of the three reconstructed distributions of iodine intake; the range of geometric mean for T4 and fT4, was 138-151.7nmol/L and 7.9-8.7pmol/L, respectively. The average value of the ratio of the 97.5th percentile to the 2.5th percentile equaled 3.1 and agreed well with similar estimates from recent observations in third-trimester pregnant women in the U.S. In addition, the reconstructed distributions of iodine intake allowed us to estimate nutrient inadequacy for late-gestation pregnant women in the U.S. via the probability approach. The prevalence of iodine inadequacy for third-trimester pregnant women in the U.S. was estimated to be between 21% and 44%. Taken together, the current work provides an improved tool for evaluating iodine nutritional status and the corresponding thyroid function status in pregnant women in the U.S. This model enables future assessments of the relevant risk of thyroid hormone level perturbations due to exposure to thyroid-active chemicals at the population-level.


Assuntos
Iodo/administração & dosagem , Modelos Teóricos , Estado Nutricional , Terceiro Trimestre da Gravidez/fisiologia , Testes de Função Tireóidea , Feminino , Humanos , Método de Monte Carlo , Gravidez , Estados Unidos
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