Long David T, Voice Thomas C
Department of Geological Sciences, Michigan State University, East Lansing, MI 48824, USA.
Croat Med J. 2007 Jun;48(3):300-11.
We evaluated the role of exposure analysis in assessing whether ochratoxin A or aristolochic acid are the agents responsible for causing Balkan endemic nephropathy. We constructed a framework for exposure analysis using the lessons learned from the study of endemic goiter within the context of an accepted general model. We used this framework to develop an exposure analysis model for Balkan endemic nephropathy, evaluated previous findings from the literature on ochratoxin A and aristolochic acid in the context of this model, discussed the strength of evidence for each, and proposed approaches to address critical outstanding questions. The pathway for exposure to ochratoxin A is well defined and there is evidence that humans have ingested ochratoxin A. Factors causing differential exposure to ochratoxin A and how ochratoxin A is implicated in Balkan endemic nephropathy are not defined. Although there is evidence of human exposure to aristolochic acid and that its effects are consistent with Balkan endemic nephropathy, a pathway for exposure to aristolochic acid has been suggested but not demonstrated. Factors causing differential exposure to aristolochic acid are not known. Exposure analysis results suggest that neither ochratoxin A nor aristolochic acid can be firmly linked to Balkan endemic nephropathy. However, this approach suggests future research directions that could provide critical evidence on exposure, which when linked with findings from the health sciences, may be able to demonstrate the cause of this disease and provide a basis for effective public health intervention strategies. One of the key unknowns for both agents is how differential exposure can occur.
我们评估了暴露分析在确定赭曲霉毒素A或马兜铃酸是否为导致巴尔干地方性肾病的致病因子方面所起的作用。我们借鉴在地方性甲状腺肿研究中获得的经验教训，在一个公认的通用模型框架内构建了暴露分析框架。我们使用该框架开发了一个针对巴尔干地方性肾病的暴露分析模型，在该模型背景下评估了以往文献中关于赭曲霉毒素A和马兜铃酸的研究结果，讨论了两者的证据强度，并提出了解决关键未决问题的方法。接触赭曲霉毒素A的途径已明确界定，且有证据表明人类摄入过赭曲霉毒素A。但导致对赭曲霉毒素A暴露差异的因素以及赭曲霉毒素A与巴尔干地方性肾病之间的关联方式尚未明确。虽然有证据表明人类接触过马兜铃酸且其作用与巴尔干地方性肾病相符，但有人提出了接触马兜铃酸的途径，但尚未得到证实。导致对马兜铃酸暴露差异的因素尚不清楚。暴露分析结果表明，赭曲霉毒素A和马兜铃酸均不能确凿地与巴尔干地方性肾病联系起来。然而，这种方法为未来的研究指明了方向，这些研究可能会提供关于暴露的关键证据，与健康科学领域的研究结果相结合后，或许能够揭示这种疾病的病因，并为有效的公共卫生干预策略提供依据。对于这两种致病因子，关键的未知因素之一是如何出现暴露差异。
