Interaction Between Phthalate Plasticizers and Calcium Oxalate: Impacts on Precipitation Behavior

Introduction:
Calcium oxalate (CaOx) is the dominant mineral phase in human kidney stones, making the understanding of its nucleation, growth, and phase selection essential for elucidating urolithiasis mechanisms. Phthalate esters are ubiquitous plasticizers with diverse hydrophobic and steric properties, and rising human exposure has increased interest in their potential interactions with urinary constituents. This study investigates how structurally distinct phthalates (DIDP, DINP, DEHP, DNOP, BBP, DBP, DIBP) influence CaOx precipitation under physiologically relevant conditions.

Methods:
CaOx was precipitated in aqueous media in the presence or absence of individual phthalates under controlled conditions (pH 6.5, ionic strength 0.05 M, 37 °C). Crystal morphology was assessed using light microscopy, and phase composition was determined by PXRD and FTIR.

Results:
In the additive‑free system, crystallization yielded exclusively COT, with crystals uniformly dispersed throughout the solution. In contrast, all phthalate-containing systems exhibited pronounced aggregation of crystals around hydrophobic additive domains. This aggregation was accompanied by clear morphological alterations, including variations in crystal dimensions and habit. While most phthalates had no measurable impact on phase composition, DINP uniquely induced partial transformation from COT to the thermodynamically more stable calcium oxalate monohydrate, indicating a structure-dependent effect on CaOx stability.

Conclusions:
Phthalate esters consistently promoted crystal aggregation and induced morphology changes, supporting predominantly surface‑mediated interactions influenced by molecular size, hydrophobicity, and chain branching. DINP was the only compound capable of modifying CaOx phase stability, likely due to its branched isononyl structure perturbing the hydration environment of COT. These findings indicate that aggregation is a common response to all tested phthalates. However, more detailed investigations are required to fully clarify the underlying mechanisms.

Funding:

This research was funded by the European Union—NextGenerationEU. Project “Advanced Interdisciplinary Approaches to Environmental Chemistry: From Materials to Sustainable Solutions for Pollution” (Grant number: 581-UNIOS-101).