You are here:
Toxicity Screening of the ToxCast Chemical Library Using a Zebrafish Developmental Assay
Citation:
PADILLA, S. J., D. L. HUNTER, B. K. PADNOS, D. CORUM, D. J. DIX, K. A. HOUCK, T. B. KNUDSEN, AND M. T. MARTIN. Toxicity Screening of the ToxCast Chemical Library Using a Zebrafish Developmental Assay. Presented at Society of Toxicology Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
NA
Description:
As part of the chemical screening and prioritization research program of the U.S. Environmental Protection Agency, the toxicity of the 320 ToxCast™ Phase I chemicals were assessed using a vertebrate screen of developmental toxicity. Zebrafish embryos/larvae (Danio rerio) were exposed from late blastula stage (approximately 6hr post fertilization, pf) to day 5pf (1 day post hatch). The 320 chemicals tested here included 309 unique chemicals, most of which are pesticide actives and metabolites, and several replicates for quality control. All exposures were by immersion, continuously, at a single concentration of 80 M. On day 5pf, fish were removed from the exposure solution to a control solution without chemicals, and on day 6pf were assessed for death and structural defects (n=4 independent embryos per chemical). Gross structural abnormalities or death was observed with 61% of the 309 chemicals. The developmental toxicity of the chemicals varied by chemical class. Classes in which all members caused either structural defects or lethality included: antiobiotics (mectins and strobins, 7 tested); conazoles (imidazoles and triazoles, 16 tested); organochlorines (4 tested); dithiocarbamates (11 tested); and pyrethroids (12 tested). Other chemical classes showed a range of positive and negative results: 4 of 10 carbamates showed no toxicity; 5 of 36 organophosphates showed no toxicity; and 2 of 6 phthalates showed no toxicity. The 6 neo-nicotinoids tested did not produce any toxicity in the developing zebrafish embryo. In conclusion, the early development of zebrafish is sensitive to many pesticides following exposure at 80 M, and that sensitivity seems to vary by chemical class. Efforts are underway to compare the response in zebrafish embryos with prenatal developmental toxicity in mammalian systems captured within the U.S. EPA ToxRefDB database. This abstract may not necessarily reflect official Agency policy.