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Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies
DUCHARME, N. A., L. E. PETERSON, E. BENFENATI, D. REIF, C. W. McCOLLUM, J. GUSTAFSSON, AND M. BONDESSON. Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies. Thomas B. Knudsen (ed.), REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 41:98-108, (2013).
Taken together, our results demonstrate that while the physical properties (BCF and logP) of a compound do not significantly correlate with lethality, teratogenicity, or most adverse developmental effects in zebrafish embryos, correlations are apparent when comparing developmental endpoints to each other. These correlations should be extended in order to ascertain a more stream-lined screening procedure for zebrafish embryo developmental toxicity. In addition, utilizing values from varying methodologies in the literature does allow the ranking of relative toxicities and teratogenicities that are in good concordance with those found in single laboratory studies. Finally, the majority of studies performed so far conclude that the correlation between zebrafish and rodent toxicity is high, promoting zebrafish screening as viable alternative to rodent toxicity testing.
Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the literature to ascertain predictive developmental toxicity endpoints. We found that the physical properties of chemicals (BCF or logP) did not fully predict lethality or developmental outcomes. Instead, individual outcomes such as pericardial edema and yolk sac edema were more reliable indicators of developmental toxicity. In addition, we ranked the chemicals based on toxicity with the Toxicological Priority Index (ToxPi) program and via a teratogenic ratio, and found that perfluorooctane sulfonate (PFOS) had the highest ToxPi score, triphenyltin acetate had the highest average ToxPi score (corrected for missing data and having more than 4 outcomes), and N-methyl-dithiocarbamate had the highest teratogenic ratio.