Abstract
The embryonic zebrafish is a powerful tool for high-throughput screening of chemicals. While this model has significant potential for use in safety assessments and chemical prioritization, a lack of exposure protocol harmonized across laboratories has limited full model adoption. To assess the potential that exposure protocols alter chemical bioactivity, we screened a set of eight chemicals and one 2D nanomaterial across four different regimens: (1) the current Tanguay laboratory’s standard protocol of dechorionated embryos and static exposure in darkness; (2) exposure with chorion intact; (3) exposure under a 14 h light: 10 h dark cycle; and (4) exposure with daily chemical renewal. The latter three regimens altered the concentrations, resulting in bioactivity of the test agents compared to that observed with the Tanguay laboratory’s standard regimen, though not directionally the same for each chemical. The results of this study indicate that with the exception for the 2D nanomaterial, the screening design did not change the conclusion regarding chemical bioactivity, just the nominal concentrations producing the observed activity. Since the goal of tier one chemical screening often is to differentiate active from non-active chemicals, researchers could consider the trade-offs regarding cost, labor, and sensitivity in their study design without altering hit rates. Taken further, these results suggest that it is reasonably feasible to reach agreement on a standardized exposure regiment, which will promote data sharing without sacrificing data content.
Highlights
There are tens of thousands of chemicals available for commerce in the United States, but relatively few have been adequately assessed for health effects [1]
Guidelines within the Organisation for Economic Cooperation and Development (OECD) Fish Embryo Acute Toxicity (FET) test address the potential for the chorion to serve as a chemical barrier, though it does not make recommendations for mechanical or enzymatic removal of the chorion [19]
This study systematically evaluated the impact of changing exposure conditions on chemical bioactivity by varying the common variables of chorion status, lighting, and chemical renewal
Summary
There are tens of thousands of chemicals available for commerce in the United States, but relatively few have been adequately assessed for health effects [1]. High-throughput bioactivity screening in the whole-animal model is the best available means to generate enough structure-activity data to allow for predicting chemical activity while supporting the goals of the “3 Rs” approach [2,3]. Most organ systems are developed and functioning by five days post fertilization (dpf) [9], and some liver cytochrome P450 enzymes are expressed as early as 72 hpf, indicating phase 1 xenobiotic metabolism [10]. These intrinsic advantages allow us to investigate how chemical exposures might interfere with complex and interacting tissues, an enormous advantage over traditional in vitro screening platforms
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