April 15, 2022
A Comparative Multi-System Approach to Characterizing Bioactivity of Commonly Occurring Chemicals
AbstractA 2019 retrospective study analyzed wristband personal samplers from fourteen different com-munities, across three different continents, for over 1530 organic chemicals. Investigators identi-fied fourteen chemicals (G14) detected in over 50% of personal samplers. The G14 represent a group of chemicals that individuals are commonly exposed to and are mainly associated with consumer products including plasticizers, fragrances, flame retardants, and pesticides. The high frequency of exposure to these chemicals raises questions of their potential adverse human health effects. Additionally, the possibility for exposure to mixtures of these chemicals is likely due to their co-occurrence, so the potential for mixtures to induce differential bioactivity warrants fur-ther investigation. We utilized a multi-system approach incorporating both in vitro and in vivo high-throughput chemical bioactivity screening to assess bioactivity of the G14 chemicals, ac-counting for both species and sensitivity differences between the two platforms. Screening of the G14 chemicals was conducted using primary normal human bronchial epithelial (NHBE) cells cultured in monolayer and early life-stage zebrafish. Bioactivity was assessed in NHBE via measurements of cytotoxicity and oxidative stress. In zebrafish, 13 morphological and two sensi-tive behavioral endpoints were assessed. Mixtures of the G14 and bioactive G14 chemicals were created to assess potential mixture interactions and potency of bioactive chemicals, and mixtures were evaluated in each model using benchmark concentration (BMC) modeling. Chemical bioac-tivity was dependent on model system, supporting the use of a multi-system approach for toxicity testing and highlighting sensitivity differences between the models. In both NHBE and zebrafish, mixtures effects were observed when screening the most active compounds relative to each model in combination. Assumption of additivity testing in a BMC-based mixture in NHBE (NHBE BMC Mix) and zebrafish (ZF BMC Mix) suggested antagonistic effects. This study describes a novel approach to broadly evaluate the hazards of chemical exposures by coupling passive chem-ical sampling with high-throughput toxicity screenings using in vitro and non-mammalian in vi-vo models. Using this approach, we were able to identify bioactive compounds in a high-throughput and high-content manner, which is not obtainable using traditional mammalian models.
Published: April 15, 2022