title: Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing.
abstract: With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates.
authors.affiliation: University of Houston, Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, Houston, TX 77204, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Ducharme
authors.affiliation: North Carolina State University, Department of Biological Sciences, Bioinformatics Research Center, Raleigh, NC 27695-7614, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Reif
authors.affiliation: University of Houston, Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, Houston, TX 77204, USA; Karolinska Institutet, Department of Biosciences and Nutrition, 14183 Huddinge, Sweden.
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.affiliation: University of Houston, Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, Houston, TX 77204, USA. Electronic address: mbondessonbolin@uh.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Bondesson
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects; D007814:Larva / Q000187:drug effects; D007928:Lethal Dose 50; D051379:Mice; D011817:Rabbits; D051381:Rats; D018675:Toxicity Tests / Q000379:methods*; D015027:Zebrafish / Q000196:embryology*
keywords: Human exposure; Meta-analysis; Teratogen; Toxicity; Zebrafish