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. 2020 Nov 1:406:115207.
doi: 10.1016/j.taap.2020.115207. Epub 2020 Aug 24.

Comparative toxicokinetics of bisphenol S in rats and mice following gavage administration

Suramya Waidyanatha  1 , Sherry R Black  2 , Melanie Silinski  2 , Vicki Sutherland  3 , Brenda L Fletcher  2 , Reshan A Fernando  2 , Timothy R Fennell  2
Affiliations

Comparative toxicokinetics of bisphenol S in rats and mice following gavage administration

Suramya Waidyanatha et al. Toxicol Appl Pharmacol. .

Abstract

Bisphenol S (BPS) is a component of polyether sulfone used in a variety of industrial applications and consumer products. We investigated the plasma toxicokinetic (TK) behavior of free (unconjugated parent) and total (parent and conjugated) BPS in rats and mice following a single gavage administration (34, 110, or 340 mg/kg). In male rats, BPS was rapidly absorbed with free BPS maximum concentration (Cmax) reached at ≤2.27 h. Elimination of free BPS in male rats was dose-dependent with estimated half-lives of 5.77-11.9 h. Cmax and area under the concentration versus time curve (AUC) increased with dose although the increase in AUC was more than dose proportional. In male rats, total BPS Cmax was reached ≤2.77 h with both Cmax (≥ 10-fold) and AUC (≥ 15-fold) higher than free BPS demonstrating rapid and extensive conjugation of BPS. In male mice, the increase in Cmax and AUC of free BPS was dose-proportional; Cmax was higher and AUC was lower than in male rats. BPS was cleared more rapidly in male mice (half-life 2.86-4.21 h) compared to male rats (half-life 5.77-11.9 h). Similar to rats, total BPS Cmax (≥ 6-fold) and AUC (≥ 12-fold) were higher than corresponding free BPS. Oral bioavailability of free BPS was low to moderate (rats, ≤ 21%; mice, ≤ 19%). There were some species differences in TK parameters of free and total BPS and limited sex difference in rats and mice. In addition, there were dose-related effects of plasma TK parameters in rats.

Keywords: Absorption; Bisphenol S; Distribution; Elimination; Oral Bioavailability; Toxicokinetics.

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Conflict of interest statement

Declaration of Competing Interest The authors report no declarations of interest.

Figures

Figure 1:
Figure 1:
Structure of bisphenol S (BPS)
Figure 2.
Figure 2.
Plasma concentration versus time profiles of free bisphenol S following a single gavage administration of 34, 110, or 340 mg/kg bisphenol S in male and female rats. One-compartmental model with first order input, first order output and 1/y were used to fit the data. Lines represent model fits. M, male; F, female.
Figure 3.
Figure 3.
Plasma concentration versus time profiles of total bisphenol S following a single gavage administration of 34, 110, or 340 mg/kg bisphenol S in male or female rats. One-compartmental model with first order input, first order output and 1/y were used to fit the data. Lines represent model fits. M, male; F, female.
Figure 4.
Figure 4.
Plasma concentration versus time profiles of A) free bisphenol S and B) total bisphenol S following a single intravenous administration of 34 mg/kg bisphenol S in male and female rats. Two compartment model with bolus input, first-order output and 1/y2 weighting was used to fit the data. Lines represent model fits. M, male; F, female.
Figure 5.
Figure 5.
Plasma concentration versus time profiles of free bisphenol S following a single gavage administration of 34, 110, or 340 mg/kg bisphenol S in male or female mice. Two compartment model with bolus input, first-order output and 1/y weighting was used for all groups Lines represent model fits. M, male; F, female.
Figure 6.
Figure 6.
Plasma concentration versus time profiles of total bisphenol S following a single gavage administration of 34, 110, or 340 mg/kg bisphenol S in male or female mice. Two compartment model with bolus input, first-order output and 1/y weighting was used for all groups using individual animal data except one compartment model with first-order input, first-order output and 1/y weighting using mean data per time point was used for 340 mg/kg total bisphenol S. Lines represent model fits. M, male; F, female.
Figure 7.
Figure 7.
Plasma concentration versus time profiles of A) free bisphenol S and B) total bisphenol S following a single intravenous administration of 34 mg/kg bisphenol S in male and female mice. Two compartment model with bolus input, first-order output and 1/y2 weighting was used to fit the data. Lines represent model fits. M, male; F, female.
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