Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing.
Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing.
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DOI：
10.1016/j.reprotox.2014.09.005
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发表时间：
2015-08-01
期刊：
影响因子：
--
通讯作者：
Bondesson M
中科院分区：
文献类型：
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作者：
Ducharme NA;Reif DM;Gustafsson JA;Bondesson M
由于哺乳动物毒性试验成本高、速度慢，脊椎动物斑马鱼已成为高通量毒性试验的易处理模式生物。我们在这里提出了一个荟萃分析600化学品测试的毒性在斑马鱼胚胎和幼虫。从已发表的研究中记录了19个聚合毒性终点和57个个体毒性终点，产生了2695个独特的数据点。将这些数据点与啮齿动物和家兔中分析的致死率和生殖毒理学终点以及人类暴露值进行比较。我们发现，虽然许多斑马鱼终点与啮齿动物或家兔急性毒性数据无关，但斑马鱼可用于准确预测大鼠吸入、家兔皮肤和大鼠口服暴露途径的相对急性毒性。根据对斑马鱼的毒性和致畸性以及人类接触水平对化学品进行的排序显示，2，3，7，8-四氯二苯并对二恶英、苯并（a）芘和毒死蜱在这三类所有化学品中排在前九位，因此应被视为在高等脊椎动物中进行测试的高度优先化学品。
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.