Department of Physical and Environmental Sciences, University of Toronto Scarborough , 1265 Military Trail, Toronto, Ontario M1C 1A4, Canada.
Environ Sci Technol. 2014 Aug 19;48(16):9770-9. doi: 10.1021/es501955g. Epub 2014 Jul 21.
Practical, financial, and ethical considerations related to conducting extensive animal testing have resulted in various initiatives to promote and expand the use of in vitro testing data for chemical evaluations. Nominal concentrations in the aqueous phase corresponding to an effect (or biological activity) are commonly reported and used to characterize toxicity (or biological response). However, the true concentration in the aqueous phase can be substantially different from the nominal. To support in vitro test design and aid the interpretation of in vitro toxicity data, we developed a mass balance model that can be parametrized and applied to represent typical in vitro test systems. The model calculates the mass distribution, freely dissolved concentrations, and cell/tissue concentrations corresponding to the initial nominal concentration and experimental conditions specified by the user. Chemical activity, a metric which can be used to assess the potential for baseline toxicity to occur, is also calculated. The model is first applied to a set of hypothetical chemicals to illustrate the degree to which test conditions (e.g., presence or absence of serum) influence the distribution of the chemical in the test system. The model is then applied to set of 1194 real substances (predominantly from the ToxCast chemical database) to calculate the potential range of concentrations and chemical activities under assumed test conditions. The model demonstrates how both concentrations and chemical activities can vary by orders of magnitude for the same nominal concentration.
进行广泛的动物测试在实际、财务和道德方面存在各种考虑因素，这导致了各种促进和扩大使用体外测试数据进行化学评估的举措。通常会报告和使用水相中的名义浓度来表示（或生物活性），以表征毒性（或生物反应）。然而，水相中的真实浓度可能与名义浓度有很大不同。为了支持体外测试设计和帮助解释体外毒性数据，我们开发了一个质量平衡模型，该模型可以参数化并应用于表示典型的体外测试系统。该模型计算与初始名义浓度和用户指定的实验条件相对应的质量分布、自由溶解浓度和细胞/组织浓度。还计算了化学活性，这是一种可以用来评估基线毒性发生的潜在可能性的指标。该模型首先应用于一组假设的化学物质，以说明测试条件（例如是否存在血清）如何影响测试系统中化学物质的分布。然后，该模型应用于一组 1194 种实际物质（主要来自 ToxCast 化学数据库），以计算在假设的测试条件下潜在的浓度和化学活性范围。该模型表明，对于相同的名义浓度，浓度和化学活性都可以相差几个数量级。
