Systematic Assessment of Exposure Variations onObserved Bioactivity in Zebrafish Chemical Screening


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 assessthe potential that exposure protocols alter chemical bioactivity, we screened a set of eight chemicalsand one 2D nanomaterial across four different regimens: (1) the current Tanguay laboratory’sstandard protocol of dechorionated embryos and static exposure in darkness; (2) exposure withchorion intact; (3) exposure under a 14 h light: 10 h dark cycle; and (4) exposure with daily chemicalrenewal. The latter three regimens altered the concentrations, resulting in bioactivity of the testagents compared to that observed with the Tanguay laboratory’s standard regimen, though notdirectionally the same for each chemical. The results of this study indicate that with the exceptionfor the 2D nanomaterial, the screening design did not change the conclusion regarding chemicalbioactivity, just the nominal concentrations producing the observed activity. Since the goal of tierone chemical screening often is to differentiate active from non-active chemicals, researchers couldconsider the trade-offs regarding cost, labor, and sensitivity in their study design without alteringhit rates. Taken further, these results suggest that it is reasonably feasible to reach agreement on astandardized exposure regiment, which will promote data sharing without sacrificing data content


See Publication :