FATE AND TRANSPORT OF ARISTOLICHIC ACIDS AS POTENTIAL EXPOSURE AGENTS RESPONSIBLE FOR BALKAN ENDEMIC NEPHROPATHY

Balkan endemic nephropathy (BEN) is a kidney disease that occurs in certain rural villages in selected Balkan countries and is thought to be linked to an environmental toxin. It was proposed that BEN could be related to exposre to Aristolochic acids (AA) found in Aristolochia clematitis (AC. AA exhibits both nephrotoxicity and carcinogenicity. Recent toxicological studies offer a growing body of evidence AA is responsible for BEN, however the exposure pathway is unclear. Here, we explore the basic fate and transport properties of AA. We hypothesize that exposure could occur as a result of the release of AA from AC and the released AA taken up by food crops. To test this hypothesis, we measured octanol-water partition coefficients (Kow) and soil sorption properties. Sorption isotherm experiments and kinetic studies were conducted using soils with different organic matter and clay contents. AA I and II were relatively hydrophyllic (log Kow < 2) under basic conditions and relatively hydrophobic (log Kow > 3) in acidic solutions. Since the pKas of AA I and II are 3.3 and 3.2, respectively, we could expect significant transport by water. Sorption isotherms of AA conformed to both the linear and Freundlich models and a positive correlation between the partition coefficient (Kd) and organic matter was observed. The linear organic-carbon-normalized partition coefficient was in the range of 3.0 – 3.5, suggesting significant uptake by high organic matter soils despite the fact that AA would be in an anionic form at the pH of the experiments. It was also observed that binding to dissolved organic matter could significantly affect transport, but this needs further study. We interpret these preliminary findings to suggest that plant uptake of AA is possible, but that additional work is necessary in order to produce quantitative estimates of exposure.