Rapid well-plate assays for motor and social behaviors in larval zebrafish.

Behavior phenotypes are a powerful means of uncovering subtle xenobiotic chemical impacts on vertebrate nervous system development. Rodents manifest complex and informative behavior phenotypes but are generally not practical models in which to screen large numbers of chemicals. Zebrafish recapitulate much of the behavioral complexity of higher vertebrates, develop externally and are amenable to assay automation. Short duration automated assays can be leveraged to screen large numbers of chemicals or comprehensive dose-response for fewer chemicals. Here we describe a series of mostly automated assays including larval photomotor response, strobe light response, blue color avoidance, shoaling and mirror stimulus-response performed on the ZebraBox (ViewPoint Behavior Technologies) instrument platform. To explore the sensitivity and uniqueness of each assay endpoint, larval cohorts from 5 to 28 days post fertilization were acutely exposed to several chemicals broadly understood to impact different neuro-activities. We highlight the throughput advantages of using the same instrument platform for multiple assays and the ability of different assays to detect unique phenotypes among different chemicals.

Tissue distribution of tetrabromobisphenol A and cadmium in mixture inhalation exposure.

Tetrabromobisphenol A (TBBPA) and cadmium chloride (CdCl2) are the typical representative pollutants of brominated flame retardants and heavy metals found in the air of e-waste recycling workshops. However, their metabolic kinetics through mixture inhalation is unknown. In the present study, 8-week old Institute of Cancer Research (ICR) male mice were whole-body exposed to TBBPA and CdCl2 mixtures by inhalation. Tissue samples were collected for TBBPA and cadmium (Cd) analysis at 2, 4, 6, and 8 weeks during exposure and at 4 and 8 weeks after the completion of the 8-week exposure period. TBBPA was mainly distributed to the lungs, liver, kidney, testis, and spleen, with a high amount accumulated in the brain, liver, and spleen. Cd was mainly distributed to the lungs, liver, and kidney, with a high amount accumulated in the liver, kidney, and testis and a low amount accumulated in brain and serum. Tissue burden of TBBPA and Cd in all organs increased in a dose- and time-dependent manner during the exposure period. However, 4 weeks after the completion of an 8-week exposure, TBBPA concentrations in the liver, testis, brain, and serum and Cd concentrations in the liver, testis, and kidney were higher than the corresponding tissue concentrations during the exposure period. The rapid accumulation of both TBBPA and Cd in the lungs after inhalation exposure indicated a high risk of the respiratory system diseases for workers in e-waste recycling workshops. In addition, the migration of both TBBPA and Cd from lungs to liver and testis may result in more complex toxic effects in vivo.