Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Time-dependent behavioral data from zebrafish reveals novel signatures of chemical toxicity using point of departure analysis.

Authors: Thomas, Dennis G; Shankaran, Harish; Truong, Lisa; Tanguay, Robert L; Waters, Katrina M

Published In Comput Toxicol, (2019 Feb)

Abstract: High-content imaging of larval zebrafish behavior can be used as a screening approach to rapidly evaluate the relative potential for chemicals to cause toxicity. However, most statistical methods applied to these data transform movement values to incidence-based "hits" and calculate lowest effect levels (LELs), which loses individual fish resolution of behavior and defies hazard ranking due to reliance on applied dose levels. We developed a parallelizable workflow to calculate benchmark dose (BMD) values from dynamic, high-content zebrafish behavior data that scales for high-throughput chemical screening. To capture the zebrafish movement response from light to dark stimulus, we summarized time-dependent data using both area under the curve and the immediate change at the transition point into two novel metrics that characterized abnormal behavior as a function of chemical concentration. The BMD workflow was applied to calculate BMD10 values of 1,060 ToxCast chemicals for 24 zebrafish endpoints, including behavior, mortality and morphology. The BMD10 values provided better precision and separation than LELs for clustering chemicals since they were derived from models that best-fit their concentration-response curves. Analysis of BMD10 values revealed behavioral signatures as the most sensitive endpoints. High concordance in chemical activity was observed between ToxCast in vitro data and zebrafish in vivo behavioral data, however ToxPi analysis indicated that rankings based on in vitro data were not a reliable predictor of in vivo rankings for lower potency chemicals. This analysis method will enable the use of high-content zebrafish behavioral screening data for BMD analysis in toxicological hazard assessment.

PubMed ID: 31485548 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

Back
to Top