The prenatal period is a particularly sensitive window of time where development can be impacted by many agents including environmental insults. Exposure to certain chemical, biological, and physical stressors during gestation have been shown to produce adverse health effects in the developing human fetus, as well as throughout an individual’s lifetime. The overall goals of this dissertation were to investigate the impacts of prenatal exposures of environmental stressors on developmental outcomes, including birthweight and neurobehavior, and to explore technologies that can be used to more quickly identify chemicals that may impact the developing fetus. First, we characterize the effects of prenatal air pollution exposure on neurobehavior in childhood. Our work demonstrates the potential impact of prenatal ambient air pollution exposure measured as fine particulate matter (particulate matter ≤ 2.5 μm; PM2.5) exposure on clinically relevant behaviors, specifically thought problems, and suggests that males may be more susceptible to air pollution-induced externalizing behavioral outcomes. In the second aim, we explore critical windows of susceptibility to the effects of various prenatal heat exposure measures on gestational growth. Our work finds that heat index variability is more strongly associated with gestational growth than other heat measures, with disproportionate effects observed in males and those experiencing homelessness during pregnancy. Our third aim compares the utilization and parameterization of New Approach Methodologies for deriving point of departure values that could serve as an alternative to the traditional hazard values derived from animal in vivo studies. Specifically, we examine pesticide chemicals with thyroid-based in vitro endpoints because of the potential impact these chemicals have on in-utero neurodevelopment. We demonstrate that pharmacokinetic model choice and dosing scenario have a substantial impact on predicted values, resulting in estimated values that can be much less restrictive than current values used in regulation. Our work highlights the need for regulators to carefully consider these choices when applying these data to hazard assessments, in order to not underestimate the potential for pesticides to impact maternal thyroid hormones. / 2023-01-24T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43683 |
| Date | 24 January 2022 |
| Creators | Carlson, Jeffrey |
| Contributors | Janulewicz Lloyd, Patricia A. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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