Thursday, January 14 2021
10:00AM – 11:15AM EST / 4:00 PM – 5:15 PM CET
Sherri Bloch, MSc, PhD student at University of Montreal
Eva Vitucci, BS, PhD Student at University of North Carolina – Chapel Hill
Register here: https://zoom.us/webinar/register/WN_wsfqCX7uQciWxA1Lu0xc_A
The Ed Carney Predictive Toxicology Award recognizes the first author of an outstanding poster or platform presentation that will advance predictive toxicology, and is named after Dr. Ed Carney, a member and supporter of the ASCCT and a leader in the predictive toxicology field. The 2020 winner was Eva C.M. Vitucci from University of North Carolina, Chapel Hill to for her presentation “Identifying the Molecular Mechanisms of Air Pollution-Induced Cardiovascular Disease”.
The Ray Tice Tox21 Student Award is presented to recognize the best student presentation during the meeting and was established with a generous donation from Dr. Ray Tice, a leader in implementing and setting the stage for Toxicity Testing in the 21st Century. The 2020 winner was Ms. Sherri Bloch from Université de Montréal for her presentation “Using in Vitro Data to Derive Acceptable Exposure Levels: A Case Study on PBDE Developmental Neurotoxicity”.
Using in vitro data to derive acceptable exposure levels: Case studies on PBDE
developmental neurotoxicity and DDE obesogenicity
Presented by: Sherri Bloch
Current acceptable exposure levels are mostly based on animal models, which are costly,
time-consuming, and may poorly predict adverse outcomes in humans. There is a need for
alternative testing methods that are faster, cheaper, and provide human-relevant information.
We aimed to evaluate a method using human in vitro data and biological modeling to calculate acceptable exposure levels through two case studies: One on PBDE developmental neurotoxicity and the other on p,p’-DDE obesogenicity due to early life exposure.
To accomplish our objectives, in vitro studies using human cells were compiled to select points of departure (POD) in the form of nominal medium concentrations. These were translated into cellular levels (target organ POD), and then converted into acceptable daily intakes and plasma concentrations in pregnant women using pharmacokinetic models of gestation/lactation and applying uncertainty factors. The final step of our methodology was the comparison of the derived chemical levels in maternal plasma to levels measured in epidemiological studies reporting associations between prenatal exposure and the adverse endpoints in children.
Estimated acceptable exposure levels and matching plasma levels showed concurrence with those measured in epidemiological studies, implying this approach may be viable. However, uncertainty factors need further investigation prior to application in risk assessment.
Identifying the Molecular Mechanisms of Air Pollution – Induced Cardiovascular Disease Presented by: Eva Vitucci
An estimated 3.5-million people die annually from air pollution-induced cardiovascular disease (API-CVD). API-thrombosis (API-T) is a main contributor of these mortalities; however, the molecular mechanisms driving API-T are unclear. To identify these mechanisms we developed an in vitro model that represents the interface of the respiratory and cardiovascular system, the alveolar capillary region (ACR). This organotypic model includes human alveolar-like epithelial cells (H441), human lung fibroblasts, and human lung microvascular endothelial cells (HULEC). We hypothesized that air pollutant exposure of the H441 cells would initiate the onset of a pro-thrombotic state in the HULEC. To test this, we exposed H441 cells to the ubiquitous air pollutant, diesel exhaust particulates (DEP), and investigated the effect of this trans-alveolar exposure (TA-DEP) on the underlying HULEC. TA-DEP exposure induced expression of anti-oxidants such as heme oxygenase 1 and NAD(P)H dehydrogenase [quinone] 1, increased nuclear factor erythoid-2 related factor (NRF2) protein, and reduced glutathione redox potential in the HULEC. Concurrently, decreased expression of the endothelial fibrinolytic and anti-coagulant genes, tissue-type plasminogen activator, plasminogen activator urokinase, and thrombomodulin, and increased expression of the procoagulant gene, coagulation factor III occurred in the HULEC. These data suggest that TA-DEP exposure induces redox dysfunction and an endothelial pro-thrombotic profile in the ACR. We conclude that redox dysfunction and pro-thrombotic activation in the capillary beds of the ACR may be critical initiation steps of API-T. Data from this model can help develop intervention strategies against API-T and can encourage the development of organotypic models resulting in a reduction of animal testing. This does not reflect EPA policy.