Department of Environmental Science, Institute of Biomedical Studies, Baylor University, Waco, TX 76798, USA.
Toxicol Lett. 2010 Mar 1;193(1):69-78. doi: 10.1016/j.toxlet.2009.12.006. Epub 2009 Dec 16.
Comparative pharmacology and toxicology approaches with fish models provide important linkages between the biomedical and environmental sciences. Because chronic fish responses to select pharmaceuticals are observed at very low (e.g., ng/L) concentrations, approaches are needed to identify therapeutics for robust environmental hazard and risk assessments. Whereas we observed no obvious relationship between acute toxicity data for rodent (LD(50)) and fish (LC(50)) models, using a probabilistic hazard evaluation approach, rodent and fish acute toxicity distributions predicted limited potential for acute toxicity at low concentrations, which is consistent with the peer-reviewed literature. Similar probabilistic distributions were developed to examine mammalian C(max) and an Acute to Therapeutic Ratio (ATR), a surrogate for mammalian therapeutic index that is similar to an Acute to Chronic Ratios (ACRs) commonly calculated for fish models. Probabilistic distributions of ATRs for fifteen drug classes were also examined, which showed specific groups with higher (e.g., reproductive hormones, corticosteroids, antihistamines) and lower (e.g., antibiotics, NSAIDs) ATR values than the distribution for all available pharmaceutical ATRs. A statistically significant relationship (r(2)=0.846, p<0.001) was determined between mammalian ATR and fish ACR values, which may support a screening approach to examine chronic pharmaceutical effects in fish based on the magnitude of mammalian ATR values.
比较药理学和毒理学方法与鱼类模型为生物医学和环境科学之间提供了重要联系。由于慢性鱼类对选择药物的反应是在非常低的浓度（例如 ng/L）下观察到的，因此需要采用方法来识别治疗药物，以进行强大的环境危害和风险评估。虽然我们没有观察到啮齿动物（LD50）和鱼类（LC50）模型的急性毒性数据之间存在明显关系，但使用概率危害评估方法，啮齿动物和鱼类急性毒性分布预测了低浓度下急性毒性的潜在可能性有限，这与同行评审文献一致。类似的概率分布也被开发出来，以检查哺乳动物的 Cmax 和急性治疗比（ATR），这是哺乳动物治疗指数的替代物，类似于通常为鱼类模型计算的急性到慢性比（ACRs）。还检查了十五种药物类别的 ATR 概率分布，结果表明某些组的 ATR 值较高（例如生殖激素、皮质类固醇、抗组胺药），而某些组的 ATR 值较低（例如抗生素、非甾体抗炎药），低于所有可用药物 ATR 的分布。确定了哺乳动物 ATR 和鱼类 ACR 值之间存在统计学上显著的关系（r2=0.846，p<0.001），这可能支持基于哺乳动物 ATR 值的大小来检查鱼类慢性药物效应的筛选方法。
