Dose and Effect Thresholds for Early Key Events in a PPARα-Mediated Mode of Action.

Current strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor alpha (PPARα).

Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio).

Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish.

Developmental exposure to valproate and ethanol alters locomotor activity and retino-tectal projection area in zebrafish embryos.

Given the minimal developmental neurotoxicity data available for the large number of new and existing chemicals, there is a critical need for alternative methods to identify and prioritize chemicals for further testing. We outline a developmental neurotoxicity screening approach using zebrafish embryos. Embryos were exposed to nominal concentrations of either valproate or ethanol then examined for lethality, malformation, nervous system structure and locomotor activity.

Zebrafish developmental screening of the ToxCast™ Phase I chemical library.

Zebrafish (Danio rerio) is an emerging toxicity screening model for both human health and ecology. As part of the Computational Toxicology Research Program of the U.S.

Assessing locomotor activity in larval zebrafish: Influence of extrinsic and intrinsic variables.

The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity.