Pacific Northwest National Laboratory, Biological Sciences Division, 902 Battelle Blvd, MS P7-58, Richland, WA 99352, USA.
Environ Toxicol Pharmacol. 2004 Nov;18(2):101-13. doi: 10.1016/j.etap.2004.05.012.
Scientific and societal interest in the analysis of aggregate toxicity derives from the fact that people are seldom exposed to single chemicals, but rather to multiple agents from different sources and even to mixtures of agents from a single source. Many descriptive terms and mathematical, graphical, and statistical models have been used to evaluate the toxicity of simple mixtures. It is not very easy to distinguish clearly the intrinsic differences, distinctions and limitations of these models when applied to characterizing interactive toxicity. A series of experiments were performed to illustrate model-dependent consistencies and differences in interactive toxicity. Cultured murine renal cortical cells, target cells for metal toxicity, were treated with selected concentrations of one metal or binary mixtures of metals to give conditions of dose-additivity, response additivity, or with only one toxic member of the binary mixture. The cytotoxicity was determined at 24h by lactate dehydrogenase release. The data were analyzed graphically and mathematically by (a) Carter's statistical isobologram, (b) Barton's non-linear, and (c) Kodell and Pounds' linear models to characterize the interaction. These models were compared and contrasted for robustness, and consistency using these common data sets. The models gave generally consistent conclusions, but each model has limitations and strengths for assessing particular mixtures scenarios. This comparison illustrates the complexity of extrapolating conclusions between models, and difficulty of public health assessment from exposures to multiple chemicals in the environment.
科学和社会对综合毒性分析的兴趣源于这样一个事实，即人们很少接触单一化学物质，而是接触来自不同来源的多种化学物质，甚至来自单一来源的化学物质混合物。已经使用了许多描述性术语和数学、图形和统计模型来评估简单混合物的毒性。当应用于描述交互毒性时，这些模型的内在差异、区别和局限性并不容易清楚地区分。进行了一系列实验，以说明交互毒性中模型依赖性的一致性和差异。培养的鼠肾皮质细胞是金属毒性的靶细胞，用选定浓度的一种金属或金属的二元混合物处理，以达到剂量相加、反应相加或二元混合物中只有一种有毒成员的条件。24 小时后通过乳酸脱氢酶释放来确定细胞毒性。通过（a）卡特的统计等对数图、（b）巴顿的非线性和（c）科德尔和庞兹的线性模型进行图形和数学分析，以描述相互作用。使用这些常见数据集比较和对比了这些模型的稳健性和一致性。这些模型得出了大致一致的结论，但每个模型在评估特定混合物情况时都有其局限性和优势。这种比较说明了在模型之间推断结论的复杂性，以及从环境中接触多种化学物质进行公共卫生评估的困难。
