Year: 2025
Type: article
Abstract: ABSTRACT The in vitro intestinal permeability of straight‐ and branched‐chain parabens has not been extensively investigated. Sixteen parabens were tested in the Caco‐2 assay. Passive diffusion was measured using PAMPA. The transport of the MCT1 substrate, p ‐coumaric acid, as well as propylparaben and isopropylparaben, was investigated. For straight‐chain parabens, P app A‐B and P app B‐A decreased with increasing chain length and LogP. P app B‐A values were similar to PAMPA permeability (P app PAMPA ), indicating passive diffusion. Losses in mass balance were due to non‐specific binding, accumulation in the cells, and/or hydrolysis to 4‐hydroxybenzoic acid (4‐HBA). The extent of hydrolysis of straight‐chain parabens was inversely proportional to their LogP, suggesting they are carboxylesterase‐1 (CES1) substrates. For C1–C5 straight‐chain parabens, P app A‐B was higher than P app B‐A , indicating vectoral permeability. Transport of parent propylparaben was passive and pH‐independent, but 4‐HBA formed was actively transported out of the cells, which was pH‐dependent. This indicated the involvement of apical MCT1 transporters (their presence was confirmed using p ‐coumaric acid). Kinetics measurements suggested that efflux of 4‐HBA is predominantly via the basolateral membrane. Branched‐chain parabens with good passive diffusion were poor CES1 substrates but may be transported via processes other than 4‐HBA MCT1 efflux. In conclusion, P app values for parabens are best calculated using parent chemical and 4‐HBA. The extent of vectoral permeability of straight‐chain but not branched‐chain parabens is correlated to the extent of hydrolysis and the concentration‐dependent contribution of passive vs. active efflux of parent and 4‐HBA, respectively.
Source: Journal of Applied Toxicology
DOI: 10.1002/jat.4917
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,940
OpenAlex ID: W4414027376