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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Briggs, GG (1973) A simple relationship between soil sorption of organic chemicals and their octanol/water partition coefficients. Proceedings of the 7th British insecticide and fungicide conference, vol 11. pp 475–478
Brooke DN, Dobbs AJ, Williams N (1986) Octanol:water partition coefficients (P): measurement, estimation and interpretation, particularly for chemicals with P > 105. Ecotoxicol Environ Saf 11:251–260
Chin YP, Weber WJ Jr, Voice TC (1986) Determination of partition coefficients and aqueous solubilities by reverse phase chromatography—II: evaluation of partitioning and solubility models. Water Res 20(11):1443–1450
Fu XF, Liu Y, Li W, Bai Y, Liao YP, Liu HW (2011) Determination of dissociation constants of aristolochic acid I and II by capillary electrophoresis with carboxymethyl chitosan-coated capillary. Talanta 85(1):813–815. https://doi.org/10.1016/j.talanta.2011.03.088
Grollman AP, Shibutani S, Moriya M, Miller F, Wu L, Moll U, Jelakovic B (2007) Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci 104(29):12129–12134. https://doi.org/10.1073/pnas.0701248104
Grover PK, Ryall RL (2005) Critical appraisal of salting-out and its implications for chemical and biological sciences. Chem Rev 105(1):1–10
Han SY, Qiao JQ, Zhang YY, Lian HZ, Ge X (2012) Determination of n-octanol/water partition coefficients of weak ionizable solutes by RP-HPLC with neutral model compounds. Talanta 97:355–361. https://doi.org/10.1016/j.talanta.2012.04.045
Hansch C, Maloney PP, Fujita T (1962) Correlation of biological activity of phenoxyacetic acids with Hammett substituent constants and partition coefficients. Nature 194(4824):178–180.
Hansch C, Leo AJ (1979) Substituent constants for correlation analysis in chemistry and biology. Wiley, New York
Ivic M (1969) Etiology of endemic nephropathy [in Serbo-Croatian]. Lijec Vjesn 91:1273–1281
Jafvert CT, Westall JC, Grieder E, Schwarzenbach RP (1990) Distribution of hydrophobic ionogenic organic compounds between octanol and water: organic acids. Environ Sci Technol 24(12):1795–1803. https://doi.org/10.1021/es00082a002
Kah M, Brown CD (2008) Log D: lipophilicity for ionisable compounds. Chemosphere 72(10):1401–1408. https://doi.org/10.1016/j.chemosphere.2008.04.074
Lee LS, Rao PSC, Nkedikizza P, Delfino JJ (1990) Influence of solvent and sorbent characteristics on distribution of pentachlorophenol in octanol–water and soil–water systems. Environ Sci Technol 24(5):654–661. https://doi.org/10.1021/es00075a006
Leo A, Hansch C, Elkins D (1971) Partition coefficients and their uses. Chem Rev 71:525–553
Long DT, Voice TC (2007) Role of exposure analysis in solving the mystery of Balkan endemic nephropath. Croat Med J 48:300–311
Lyman WJ, Reehl WF, Rosenblatt DH (1990) Handbook of chemical proiperty estimation methods. American Chemical Society, Washington, DC
McCall JM (1975) Liquid–liquid partition coefficients by high-pressure liquid chromatograpy. J Med Chem 18(6):549–552
McDuffie B (1981) Estimation of octanol/water partition coefficients for organic pollutants using reverse-phase HPLC. Chemosphere 10:73–83
Meyer H (1899) Zur Theorie der Alkolnarkose. Naunyn-Schmiedeberg’s Archives of Pharmacology 42(2–4):109
Nowosielski BE, Fein JB (1998) Experimental study of octanol–water partition coefficients for 2,4,6-trichlorophenol and pentachlorophenol: derivation of an empirical model of chlorophenol partitioning behaviour. Appl Geochem 13(7):893–904. https://doi.org/10.1016/s0883-2927(98)00015-8
OECD (1995) Method 107—partition coefficient (n-octanol/water): shake flask method. OECD Guideline for the testing of chemicals. https://www.oecd-ilibrary.org/docserver/9789264069626-en.pdf?expires=1553262124&id=id&accname=ocid177642&checksum=AE84923B7DF17902631180FC292C9F89. Accessed 22 Mar 2019
Overton E (1899) Ueber die allgemeinen osmotischen Eigenschaften der Zelle, ihre vermutlichen Ursachen und ihre Bedeutung fur die Physuikigue. Vierteljahrsshcrift der Nauturforschenden Gesellschaft in Zürich 44:88–135
Pavlović NM, Maksimović JD, Orem WH, Tatu CA, Lerch HE, Bunnell JE, Kostić EN, Szilagyi DN, Paunescu V (2013) Possible heath impacts of naturally occuring uptake of aristolichic acids by maize and cucumber roots: links to the etiology of endemic (Balkan) nephropathy. Environ Geochem Health 35:215–226
Schwartzenbach RP, Gschwend PM, Imboden DM (2017) Environmental organic chemistry. Wiley, New York
Tangtong C, Qiao L, Long DT, Voice TC (2013) Fate and transport properties of aristolochic acids as potential exposure agents responsible for Balkan endemic nephropathy. In: Proceedings of the 13th international conference on environmental science and technology, Athens, Greece, September 5–7, 2013
Westall JC, Leuenberger C, Schwarzenbach RP (1985) Influence of pH and ionic-strength on the aqueous nonaqueous distribution of chlorinated phenols. Environ Sci Technol 19(2):193–198. https://doi.org/10.1021/es00132a014
Acknowledgements
This study was supported in part by Grant 5D43 TW00641 from the Fogarty International Center, National Institutes of Health, USA. The doctoral study of C. Tangtong was supported by the Royal Thai Government.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Tangtong, C., Qiao, L., Long, D.T. et al. Octanol–Water Partition Coefficients of Aristolochic Acids and Implications to the Etiology of Balkan Endemic Nephropathy. Aquat Geochem 26, 183–190 (2020). https://doi.org/10.1007/s10498-019-09367-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10498-019-09367-6