Development of an LC-MS/MS method for the simultaneous quantification of 11 perfluoroalkyl compounds in mouse plasma for toxicokinetic applications.

Following regulatory pressure, the manufacture of long-chain per- and polyfluoroalkyl substances (PFAS) has been phased out, and alternatives such as short-chain homologs and ether-PFAS have replaced the bioaccumulative long-chain PFAS. However, data are lacking regarding the toxicokinetic (TK) properties of certain PFAS, particularly emergent substitutes for long-chain compounds. Additionally, the existing analytical methods used for TK studies measure a single compound or only a few simultaneously.

Short-Half-Life Chemicals: Maternal Exposure and Offspring Health Consequences-The Case of Synthetic Phenols, Parabens, and Phthalates.

Phenols, parabens, and phthalates (PPPs) are suspected or known endocrine disruptors. They are used in consumer products that pregnant women and their progeny are exposed to daily through the placenta, which could affect offspring health. This review aims to compile data from cohort studies and in vitro and in vivo models to provide a summary regarding placental transfer, fetoplacental development, and the predisposition to adult diseases resulting from maternal exposure to PPPs during the gestational period.

Herd-level associations between the proportion of elevated prepartum nonesterified fatty acid concentrations and postpartum diseases, reproduction, or culling on dairy farms.

The objectives of this herd-level prospective observational cohort study were to describe the proportion of cows with elevated prepartum nonesterified fatty acid concentrations (PropElevNEFA) in dairy herds and to assess the herd-level associations between PropElevNEFA and postpartum diseases, reproductive performance, and culling. From November 2018 to December 2020, a convenience sample of 49 herds was enrolled in this study. Blood sampling (16 to 29 cows per herd) was performed during the week before and during the 2 wk following calving to quantify the concentration of nonesterified fatty acids (NEFA) and β-hydroxybutyrate acids (BHBA), respectively.

Importance of relative binding of bisphenol A and bisphenol S to plasma proteins for predicting their in vivo potencies.

Many studies suggest that the potential impact of bisphenol S (BPS) as an endocrine disruptor is comparable to that of bisphenol A (BPA). However, in vitro-to-in vivo and from animal to human extrapolations require knowledge of the plasma free fraction of the active endocrine compounds. The present study aimed to characterise BPA and BPS binding to plasma proteins both in humans and different animal species.

Contribution of Reliable Chromatographic Data in QSAR for Modelling Bisphenol Transport across the Human Placenta Barrier.

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as BPAF, BPAP, BPB, BPF, BPP, BPS, and BPZ. However, these alternatives are under surveillance for potential endocrine disruption, particularly during the critical period of fetal development. Despite their structural analogies, these BPs differ greatly in their placental transport efficiency.

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

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.

Association between prepartum nonesterified fatty acid serum concentrations and postpartum diseases in dairy cows.

The objective of the present study was to quantify the relationships between prepartum nonesterified fatty acid (NEFA) concentrations and the development of subsequent diseases or culling and to identify the optimal thresholds allowing identification of animals at high risk of developing postpartum diseases or being culled. A total of 1,299 Holstein cows from 50 commercial herds located around Saint-Hyacinthe (QC, Canada) were enrolled in this observational study. Blood samples were collected from enrolled cows between 1 and 14 d before calving for serum NEFA quantification.

Gestational exposure to bisphenol A induces region-specific changes in brain metabolomic fingerprints in sheep.

Fetal brain development depends on maternofetal thyroid function. In rodents and sheep, perinatal BPA exposure is associated with maternal and/or fetal thyroid disruption and alterations in central nervous system development as demonstrated by metabolic modulations in the encephala of mice. We hypothesized that a gestational exposure to a low dose of BPA affects maternofetal thyroid function and fetal brain development in a region-specific manner.

Are BPA Substitutes as Obesogenic as BPA?

Metabolic diseases, such as obesity, Type II diabetes and hepatic steatosis, are a significant public health concern affecting more than half a billion people worldwide. The prevalence of these diseases is constantly increasing in developed countries, affecting all age groups. The pathogenesis of metabolic diseases is complex and multifactorial.

Regulatory and academic studies to derive reference values for human health: The case of bisphenol S.

The close structural analogy of bisphenol (BP) S with BPA, a recognized endocrine-disrupting chemical and a substance of very high concern in the European Union, highlights the need to assess the extent of similarities between the two compounds and carefully scrutinize BPS potential toxicity for human health. This analysis aimed to investigate human health toxicity data regarding BPS, to find a point of departure for the derivation of human guidance values. A systematic and transparent methodology was applied to determine whether European or international reference values have been established for BPS.

Miniaturized Electrochemical Sensors to Monitor Fetal Hypoxia and Acidosis in a Pregnant Sheep Model.

Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously.

Comparison of the materno-fetal transfer of fifteen structurally related bisphenol analogues using an ex vivo human placental perfusion model.

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by a variety of alternatives in consumer products. Due to their structural similarity to BPA, these alternatives are under surveillance, however, for potential endocrine disruption. Understanding the materno-fetal transfer of these BPA-related alternatives across the placenta is therefore crucial to assess prenatal exposure risks.

Lifetime dietary exposure to bisphenol A in the general population and during pregnancy: Foetal exposure and health risk assessment.

Bisphenol A is a well-known chemical substance triggering reprotoxic and endocrine disruptor effects. Pregnancy is considered as a critical period of exposure to BPA because of the foetal sensitivity to endocrine disruption. Because of its wide use in food packaging, BPA is found in common foods and in infant formulae.

A new LC/MS method for specific determination of human systemic exposure to bisphenol A, F and S through their metabolites: Application to cord blood samples.

Due to restriction of the use of BPA, several structural analogues such as BPS and BPF have been proposed for its replacement in many consumer products. This has increased the prevalence of BPS and BPF in urine from tested cohorts. However, these substitutes have similar endocrine disrupting properties to BPA, particularly on reproductive and metabolic functions, which suggests that fetal exposure to these analogues could be of concern for human health.

Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO nanoparticles in an ex vivo placental perfusion model.

Background: Titanium dioxide (TiO) is broadly used in common consumer goods, including as a food additive (E171 in Europe) for colouring and opacifying properties. The E171 additive contains TiO nanoparticles (NPs), part of them being absorbed in the intestine and accumulated in several systemic organs. Exposure to TiO-NPs in rodents during pregnancy resulted in alteration of placental functions and a materno-foetal transfer of NPs, both with toxic effects on the foetus.

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

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.

Toward a better understanding of the effects of endocrine disrupting compounds on health: Human-relevant case studies from sheep models.

There are many challenges to overcome in order to properly understand both the exposure to, and effects of, endocrine disruptors (EDs). This is particularly true with respect to fetal life where ED exposures are a major issue requiring toxicokinetic studies of materno-fetal exchange and identification of pathophysiological consequences. The sheep, a large, monotocous, species, is very suitable for in utero fetal catheterization allowing a modelling approach predictive of human fetal exposure.

Toxicokinetics of bisphenol S in rats for predicting human bisphenol S clearance from allometric scaling.

Previous data obtained in piglets suggested that despite structural analogy with Bisphenol A (BPA), Bisphenol S (BPS) elimination may proceed more slowly, resulting in a much higher systemic exposure to unconjugated BPS than to BPA. Interspecies allometric scaling was applied to predict the toxicokinetic (TK) parameters of BPS, namely plasma clearance in humans from values obtained in animals, and thus contribute to assessment of the human internal exposure to BPS. Allometric scaling was performed using mean BPS plasma clearance values measured in rats after intravenous administration of 5 mg BPS /kg body weight (BW) and those previously obtained in piglets and sheep using identical IV BPS dosing and analytical procedures.

Evidence for Bisphenol B Endocrine Properties: Scientific and Regulatory Perspectives.

Background: The substitution of bisphenol A (BPA) by bisphenol B (BPB), a very close structural analog, stresses the need to assess its potential endocrine properties.

Objective: This analysis aimed to investigate whether BPB has endocrine disruptive properties in humans and in wildlife as defined by the World Health Organization (WHO) definition used in the regulatory field, that is, ) adverse effects, ) endocrine activity, and ) plausible mechanistic links between the observed endocrine activity and adverse effects.

Methods: We conducted a systematic review to identify BPB adverse effects and endocrine activities by focusing on animal models and mechanistic studies.

Dietary exposure to perfluoroalkyl acids, brominated flame retardants and health risk assessment in the French infant total diet study.

Perfluoroalkyl acids (PFAAs) and brominated flame retardants (BFRs) are widely used and present in human food. Due to the increased susceptibility to pollutants of the young children, we conducted a total diet study focusing on this population. Around 200 baby and common food composite samples, prepared "as consumed", have been analysed for PFAAS, hexabromocyclododecanes, polybrominated biphenyls, polybrominated diphenyl ethers and tetrabromobisphenol A.

Is bisphenol S a safer alternative to bisphenol A in terms of potential fetal exposure ? Placental transfer across the perfused human placenta.

The aim of our study was to evaluate the bidirectional transfer of Bisphenol S (BPS) and its main metabolite, BPS Glucuronide (BPSG), using the model of perfused human placenta and to compare the obtained values with those of Bisphenol A (BPA) and BPA Glucuronide. Fourteen placentas at term were perfused in an open dual circuit with deuterated BPS (1 and 5 μM) and non-labelled BPSG (2.5 μM) and a freely diffusing marker antipyrine (800 ng/ml) in the presence of albumin (25 mg/ml).