Octanol–Water Partition Coefficients of Aristolochic Acids and Implications to the Etiology of Balkan Endemic Nephropathy

Abstract

The octanol–water partition coefficients (Kow) of the aristolochic acids, AA I and AA II, were determined using the traditional shake-flask method as a function of pH and ionic strength. These compounds have been implicated in the etiology of Balkan endemic nephropathy, but evidence of a plausible exposure pathway remains elusive, and research is constrained by the absence of critical physical–chemical parameters on these compounds. Apparent Kow values were determined across a range of pH and ionic strength conditions. The results show that the apparent Kow decreased by approximately four orders of magnitude as pH increased from 2 to 9. The pH dependence was well described by a simple model that calculated the apparent Kow based on the ionization fractions and intrinsic Kow values for the neutral and ionized species. Higher ionic strength solutions resulted in higher Kow values at high pH, but had no effect at low pH. These results suggest that transport of aristolochic acids will be highly dependent on pH and ionic strength, with significant aqueous-phase transport at neutral to slightly alkaline conditions, with the highest mobility occurring under low ionic strength conditions, and the possibility of significant partitioning to nonpolar phases, such as soil organic matter or plant material, at low pH. Much of the region where BEN is prevalent is a karst environment, and pH values are generally above 8, thus leaching and groundwater transport are favored, which can suggest possible exposure routes.

Full text

Vol.:(0123456789)
Aquatic Geochemistry (2020) 26:183–190
https://doi.org/10.1007/s10498-019-09367-6
1 3
ORIGINAL ARTICLE
Octanol–Water Partition Coecients ofAristolochic
Acids andImplications totheEtiology ofBalkan Endemic
Nephropathy
ChaiyanunTangtong1· LuluQiao1· DavidT.Long1,2,3· ThomasC.Voice1,2,3
Received: 2 April 2019 / Accepted: 27 December 2019 / Published online: 5 May 2020
© Springer Nature B.V. 2020
Abstract
The octanol–water partition coefficients (Kow) of the aristolochic acids, AA I and AA II,
were determined using the traditional shake-flask method as a function of pH and ionic
strength. These compounds have been implicated in the etiology of Balkan endemic
nephropathy, but evidence of a plausible exposure pathway remains elusive, and research is
constrained by the absence of critical physical–chemical parameters on these compounds.
Apparent Kow values were determined across a range of pH and ionic strength conditions.
The results show that the apparent Kow decreased by approximately four orders of mag-
nitude as pH increased from 2 to 9. The pH dependence was well described by a simple
model that calculated the apparent Kow based on the ionization fractions and intrinsic Kow
values for the neutral and ionized species. Higher ionic strength solutions resulted in higher
Kow values at high pH, but had no effect at low pH. These results suggest that transport
of aristolochic acids will be highly dependent on pH and ionic strength, with significant
aqueous-phase transport at neutral to slightly alkaline conditions, with the highest mobility
occurring under low ionic strength conditions, and the possibility of significant partition-
ing to nonpolar phases, such as soil organic matter or plant material, at low pH. Much of
the region where BEN is prevalent is a karst environment, and pH values are generally
above 8, thus leaching and groundwater transport are favored, which can suggest possible
exposure routes.
Keywords Octanol–water partition coefficient· Aristolochic acid· Balkan endemic
nephropathy
* Thomas C. Voice
voice@msu.edu
1 Civil andEnvironmental Engineering, Michigan State University, EastLansing, MI, USA
2 Geological Sciences, Michigan State University, EastLansing, MI, USA
3 Institute forGlobal Health, Michigan State University, EastLansing, MI, USA
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