Comparison of toxicokinetic properties of eleven analogues of Bisphenol A in pig after intravenous and oral administrations. (January 2023)

• Record Type: Journal Article
• Authors: Gély, Clémence A.; Lacroix, Marlène Z.; Roques, Béatrice B.; Toutain, Pierre-Louis; Gayrard, Véronique; Picard-Hagen, Nicole
• Is Part Of: Environment international. Volume 171(2023)
• Publication Date: 2023-01
• Subjects: Bisphenols -- Toxicokinetics -- Oral exposure -- Mixture -- Pig model; TK Toxicokinetics -- BPs Bisphenols -- BPF Bisphenol F -- BPA Bisphenol A -- BPB Bisphenol B -- BPAF Bisphenol AF -- 3-3BPA 2, 2-Bis(4-hydroxy-3-methylphenyl)propane -- BPZ Bisphenol Z -- BPM Bisphenol M -- BPS Bisphenol S -- BP4-4 4, 4′-Dihydroxybiphenyl -- BPAP Bisphenol AP -- BPFL Bisphenol FL -- BPP Bisphenol P -- DHDPE Bis(4-hydroxyphenyl) Ether 4, 4′-Oxydiphenol. LOQ, limit of quantification -- QC Quality Control -- UHPLC ultra-high performance liquid chromatography -- NCA non-compartmental approach -- NLME NonLinear Mixed Effect modeling -- HTTK High-Throughput Toxicokinetics. Vss, steady-state volume of distribution -- AUC area under the concentration-time curve -- MRT Mean Residence Time -- Cl Clearance -- F Bioavailability -- Cl_F apparent clearance -- HL terminal Half- life; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2022.107722
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: The mixture approach used in this toxicokinetic study allows reducing animal testing. Bisphenol S results in the highest systemic exposure compared to other bisphenols. The urinary excretion differs greatly among 12 bisphenols. Urine biomonitoring does not reflect the external exposure for some bisphenols. Abstract: Due to the restrictions of its use, Bisphenol A (BPA) has been replaced by many structurally related bisphenols (BPs) in consumer products. The endocrine disrupting potential similar to that of BPA has been described for several bisphenols, there is therefore an urgent need of toxicokinetic (TK) data for these emerging BPs in order to evaluate if their internal exposure could increase the risk of endocrine disruption. We investigated TK behaviors of eleven BPA substitutes (BPS, BPAF, BPB, BPF, BPM, BPZ, 3-3BPA, BP4-4, BPAP, BPP, and BPFL) by intravenous and oral administrations of mixtures of them to piglets and serial collection of blood over 72 h and urine over 24 h, to evaluate their disposition. Data were analyzed using nonlinear mixed-effects modeling and a comparison was made with TK predicted by the generic model HTTK package. The low urinary excretion of some BPs, in particular BPM, BPP and BPFL, is an important aspect to consider in predicting human exposure based on urine biomonitoring. Despite their structural similarities, for the same oral dose, all BPA analogues investigated showed a higher systemic exposure (area under the plasma concentration-time curve (AUC) of the unconjugated Bisphenol) than BPA (2 to 4 fold for 3-3BPA, BPAF, BPB and BPZ, 7–20 fold for BP4-4, BPAP, BPP, BPFL, BPF and BPM and 150 fold for BPS) due mainly to a considerable variation of oral bioavailability (proportion of BP administered by oral route that attains the systemic circulation unchanged). Given similarities in the digestive tract between pigs and humans, our TK data suggest that replacing BPA with some of its alternatives, particularly BPS, will likely lead to higher internal exposure to potential endocrine disruptive compounds. These findings are crucial for evaluating the risk of human exposure to these emerging BPs.