Toxicokinetics of bisphenol A, bisphenol S, and bisphenol F in a pregnancy sheep model

Abstract

Bisphenol A (BPA), S (BPS), and F (BPF) are among the most abundant bisphenols detected in humans, yet pregnancy toxicokinetics for BPS or BPF remain unknown. Because gestational BPS can disrupt placental function and result in reproductive and metabolic disorders in the progeny, the aim of the study was to investigate BPS and BPF toxicokinetics during pregnancy using an in vivo approach. Fetal catheterizations were conducted in pregnant sheep (n = 6) at mid-pregnancy and injected with either a single dose of BPS (n = 3, 0.5 mg/kg, s.c.), or a combination of BPS, BPF, and BPA (n = 3, 0.5 mg/kg for each chemical, s.c.). Maternal and fetal blood and urine and amniotic fluid were collected over 72h and analyzed for bisphenols by HPLC-MS/MS. We observed significant differences in half-life, maximum concentration, and total body clearance in maternal circulation among bisphenols. Longer half-lives were observed in fetal vs. maternal circulation for all bisphenols. Fetal toxicokinetics differed among bisphenols with BPS having the longest fetal half-life. All bisphenols reached basal levels at 48h in maternal plasma, but were still detectable in amniotic fluid, fetal urine, and fetal plasma at 72h. In this first pregnancy toxicokinetic study of BPS and BPF we have demonstrated maternal and fetal oxicokinetic differences among all three bisphenols. Higher BPS persistence in the fetal compartment warrants studies into progeny adverse outcomes following gestational exposure. Additionally, toxicokinetic

Developmental programming: Sex‐specific programming of growth upon prenatal bisphenol A exposure

“…Consistent with the transplacental transfer of BPA seen in earlier studies (Balakrishnan, Henare, Thorstensen, Ponnampalam, & Mitchell, ; Gingrich et al, ; Ikezuki et al, ; Schonfelder et al, ), we observed transplacental transfer of BPA to the fetus with measurable concentrations of free BPA detectable in umbilical cord blood. In this assessment of chronic BPA exposure at two time points during pregnancy (GD65 and GD90 of a 147‐day gestation pregnancy), concentrations of free and total BPA in maternal circulation were comparable between GD65 and GD90, indicative of the short half‐life and fast clearance of BPA reported in earlier studies (Collet et al, ; Gingrich et al, ; Viguie et al, ) and supportive of a lack of an accummulation of BPA in the maternal compartment after chronic BPA exposure.…”

Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk

“…Eight non-pregnant adult sheep (Polypay × Dorset) were used as control. Pregnant sheep were housed indoors and their total mixed ration adjusted to energy requirements for pregnancy and lactation ( National Research Council, 2007 ) as previously described ( Gingrich et al, 2019 ). Offspring were housed with their mothers.…”

Plasticizers and Cardiovascular Health: Role of Adipose Tissue Dysfunction

“…Studies show that bisphenols cross the placenta and accumulate in fetal tissues at levels higher than maternal serum (Ikezuki et al, 2002;Gerona et al, 2013). This may be due to immature detoxification defences, leading to slower clearance of bisphenols from the fetal compartment, as demonstrated by studies in pregnant sheep (Corbel et al, 2015;Gingrich et al, 2019). The fetus is particularly vulnerable to the endocrine disrupting effects of bisphenols and other xenobiotics as it is undergoing critical developmental stages of organ maturation and setting of endocrine axes.…”