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.

Keywords: Human exposure; Meta-analysis; Teratogen; Toxicity; Zebrafish.

Fig. 1

Correlation between selected rodent and rabbit lethal dose/concentrations and zebrafish embryo toxicity outcomes. (a) The LC50 for zebrafish at 96 hpf was plotted against the LC50 rat inhalation values. The R² value for the line is 0.74. (b) The concentration of a chemical causing an alteration in zebrafish spontaneous movement was plotted against the LD50 oral rat value. The R² value for the line is 0.76. (c) The concentrations of a chemical causing a change in zebrafish touch response or decreased heart rate were plotted against the LD50 rabbit dermal value. The R² for the both outcomes is 0.91.