Minimizing Experimental Testing on Fish for Legacy Pharmaceuticals.
Minimizing Experimental Testing on Fish for Legacy Pharmaceuticals.
复制标题
最大程度地减少对遗产药物的鱼类的实验测试。
DOI：
10.1021/acs.est.2c07222
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发表时间：
2023-01-31
影响因子：
11.4
通讯作者：
Tyler, Charles R.
中科院分区：
文献类型：
--
作者：
Coors, Anja;Brown, A. Ross;Maynard, Samuel K.;Perkins, Alison Nimrod;Owen, Stewart;Tyler, Charles R.
在2006年前，没有对授权的人类药物进行生态毒理测试的监管要求，其中许多药物几乎没有或根本没有数据来评估其环境风险。出于动物福利的考虑，我们开发了一种决策树，以最大限度地减少对此类遗留活性药物成分(API)的体内鱼类测试。使用最小无效果浓度(NOECmin，来自慢性水蚤和藻类毒性研究的最低NOEC)、理论治疗水浓度(TWC，使用鱼血浆模型计算)和预测环境浓度(PEC/NOECmin和PEC/TWC)来计算API风险商。基于96种原料药的验证数据集，我们表明，通过将两个风险商数的阈值设置为0.001，在不降低环境保护水平的情况下，体内鱼类测试的需要可能减少约35%。因此，对于大多数原料药来说，对NOECMIN采用1000的评估系数(相当于阈值0.001)可以可靠地取代NOECFISH，而TWC则是其他原料药的有效安全网。硅胶和体外数据以及哺乳动物毒性数据可能进一步支持关于是否需要进行鱼类测试的最终决定。用于遗留人类药物环境风险评估的最小化鱼类试验的决策树。
There was no regulatory requirement for ecotoxicological testing of human pharmaceuticals authorized before 2006, and many of these have little or no data available to assess their environmental risk. Motivated by animal welfare considerations, we developed a decision tree to minimize in vivo fish testing for such legacy active pharmaceutical ingredients (APIs). The minimum no observed effect concentration (NOECmin, the lowest NOEC from chronic Daphnia and algal toxicity studies), the theoretical therapeutic water concentration (TWC, calculated using the fish plasma model), and the predicted environmental concentration (PEC) were used to derive API risk quotients (PEC/NOECmin and PEC/TWC). Based on a verification data set of 96 APIs, we show that by setting a threshold value of 0.001 for both risk quotients, the need for in vivo fish testing could potentially be reduced by around 35% without lowering the level of environmental protection. Hence, for most APIs, applying an assessment factor of 1000 (equivalent to the threshold of 0.001) to NOECmin substituted reliably for NOECfish, and TWC acted as an effective safety net for the others. In silico and in vitro data and mammalian toxicity data may further support the final decision on the need for fish testing. A decision tree for minimizing testing in fish for the environmental risk assessment of legacy human pharmaceuticals.
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DOI：
10.1016/j.scitotenv.2018.08.122
发表时间：
2019-01-15
期刊：
The Science of the total environment
影响因子：
--
作者：
Miller TH;Gallidabino MD;MacRae JI;Owen SF;Bury NR;Barron LP
通讯作者：
Barron LP
影响因子：
11.8
作者：
Gunnarsson, Lina;Snapk, Jason R.;Tyler, Charles R.
通讯作者：
Tyler, Charles R.
影响因子：
3.7
作者：
Margiotta-Casaluci L;Owen SF;Cumming RI;de Polo A;Winter MJ;Panter GH;Rand-Weaver M;Sumpter JP
通讯作者：
Sumpter JP
影响因子：
1.8
作者：
Kienzler, Aude;Halder, Marlies;Worth, Andrew
通讯作者：
Worth, Andrew
影响因子：
4.5
作者：
Fitzsimmons, PN;Fernandez, JD;Nichols, JW
通讯作者：
Nichols, JW