Toxicokinetics of bisphenol-S and its glucuronide in plasma and urine following oral and dermal exposure in volunteers for the interpretation of biomonitoring data

• Published in: Environment international 2020-05, Vol.138, p.105644, Article 105644
• Main Authors: Khmiri, Imèn, Côté, Jonathan, Mantha, Marc, Khemiri, Rania, Lacroix, Marlène, Gely, Clémence, Toutain, Pierre-Louis, Picard-Hagen, Nicole, Gayrard, Véronique, Bouchard, Michèle
• Format: Article
• Language: English
• Subjects: Biomarkers of exposure; Bisphenol S; Bisphenol S glucuronide; Cutaneous exposure; Human health and pathology; Life Sciences; Oral exposure; Toxicology
• ISSN: 0160-4120; 1873-6750
• DOI: 10.1016/j.envint.2020.105644

•Oral kinetics of BPS-d8 and BPSG-d8 showed a rapid appearance and elimination.•There was a higher oral bioavailability of active BPS than BPA.•Major differences between BPS and BPA oral kinetics were evidenced.•Dermal absorption of BPS was limited.•Replacement of BPA by BPS could increase exposure to a hormonally active substance. The measurement of bisphenol-S (BPS) and its glucurono-conjugate (BPSG) in urine may be used for the biomonitoring of exposure in populations. However, this requires a thorough knowledge of their toxicokinetics. The time courses of BPS and BPSG were assessed in accessible biological matrices of orally and dermally exposed volunteers. Under the approval of the Research Ethics Committee of the University of Montreal, six volunteers were orally exposed to a BPS-d8 deuterated dose of 0.1 mg/kg body weight (bw). One month later, 1 mg/kg bw of BPS-d8 were applied on 40 cm2 of the forearm and then washed 6 h after application. Blood samples were taken prior to dosing and at fixed time periods over 48 h after treatment; complete urine voids were collected pre-exposure and at pre-established intervals over 72 h postdosing. Following oral exposure, the plasma concentration–time courses of BPS-d8 and BPSG-d8 over 48 h evolved in parallel, and showed a rapid appearance and elimination. Average peak values (±SD) were reached at 0.7 ± 0.1 and 1.1 ± 0.4 h postdosing and mean (±SD) apparent elimination half-lives (t½) of 7.9 ± 1.1 and 9.3 ± 7.0 h were calculated from the terminal phase of BPS-d8 and BPSG-d8 in plasma, respectively. The fraction of BPS-d8 reaching the systemic circulation unchanged (i.e. bioavailability) was further estimated at 62 ± 5% on average (±SD) and the systemic plasma clearance at 0.57 ± 0.07 L/kg bw/h. Plasma concentration–time courses and urinary excretion rate profiles roughly evolved in parallel for both substances, as expected. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 over the 0–72 h period postdosing was 1.72 ± 1.3 and 54 ± 10%. Following dermal application, plasma levels were under the lower limit of quantification (LLOQ) at most time points. However, peak values were reached between 5 and 8 h depending on individuals, suggesting a slower absorption rate compared to oral exposure. Similarly, limited amounts of BPS-d8 and its conjugate were recovered in urine and peak excretion rates were reached between 5 and 11 h postdosing. The average percent (±SD) of the admi