Department of Environmental and Occupational Health, School of Rural Public Health, Texas A&M University System Health Science Center, Wells Fargo Plaza, 3000 Briarcrest Dr #300, Bryan, TX 77802, USA; College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
Environ Toxicol Pharmacol. 2004 Nov;18(2):135-41. doi: 10.1016/j.etap.2004.03.013.
One of the initial steps in remediating contaminated environments is to assess the human and ecological health risk associated with exposure to contaminants in a specific medium. Presented here are the results of a five-year study investigating the toxicity of simple and complex mixtures. A series of model compounds and simple mixtures including polycyclic aromatic hydrocarbons (PAHs), pentachlorophenol (PCP), and halogenated aliphatic hydrocarbons (HAHs) were analyzed. Mixture toxicity was studied using microbial genotoxicity assays and cytotoxicity assays with renal and neural cells. The majority of binary mixtures described here induced additive responses. A limited number of samples were identified where binary mixtures induced inhibitory effects. For example, benzo(a)pyrene (BAP) alone induced 30% renal cell death, whereas an equimolar dose of chrysene and BAP only produced 1.6% cellular death. In none of the mixtures tested did the mixture toxicity results deviate from the predicted results by an order of magnitude. The results from testing binary mixtures in this study indicate that the results did not deviate significantly from additivity. Complex mixture results were more difficult to interpret. The toxicity of complex mixtures could not be accurately predicted based on chemical analysis. This could be due to chemical interactions or due to the presence of unidentified chemicals, such as alkyl PAHs or high molecular weight PAHs that are not included in the standard risk assessment procedure. Even though the results from these in vitro studies indicate that additive assumptions will generally be appropriate for binary mixtures similar to the ones tested here, the risk associated with complex mixtures remains a challenge to predict. Before the results of toxicity testing can be used to adjust risk assessment calculations, it is important to fully appreciate the chemical composition and to understand the mechanism of observed chemical interactions in animals chronically exposed to low doses of chemical mixtures. This research was supported by ATSDR Grant no. ATU684505 and NIEHS SBRP Grant no. P42 ES04917.
在修复受污染的环境时，首要步骤之一是评估人类和生态健康风险，以确定与特定介质中污染物暴露相关的风险。本文介绍了一项为期五年的研究结果，该研究调查了简单和复杂混合物的毒性。分析了一系列模型化合物和简单混合物，包括多环芳烃 (PAHs)、五氯苯酚 (PCP) 和卤代脂肪烃 (HAHs)。使用微生物遗传毒性测定和肾细胞和神经细胞的细胞毒性测定来研究混合物毒性。这里描述的大多数二元混合物诱导了加性反应。有少数样品被鉴定为二元混合物诱导了抑制作用。例如，苯并 (a) 芘 (BAP) 单独诱导 30%的肾细胞死亡，而等量的䓛和 BAP 仅产生 1.6%的细胞死亡。在测试的混合物中，没有一种混合物的毒性结果偏离预测结果一个数量级。本研究中测试二元混合物的结果表明，结果没有明显偏离加性。复杂混合物的结果更难解释。复杂混合物的毒性不能仅根据化学分析来准确预测。这可能是由于化学相互作用，也可能是由于存在未识别的化学物质，如烷基多环芳烃或高分子量多环芳烃，这些物质不包括在标准风险评估程序中。尽管这些体外研究的结果表明，对于类似于这里测试的二元混合物，加性假设通常是合适的，但对于复杂混合物的风险预测仍然是一个挑战。在毒性测试结果可用于调整风险评估计算之前，必须充分了解化学组成，并了解动物在慢性低剂量接触化学混合物时观察到的化学相互作用的机制。这项研究得到了 ATSDR 资助号 ATU684505 和 NIEHS SBRP 资助号 P42 ES04917 的支持。
