Pharmacokinetics of bisphenol A in humans following dermal administration

Sasso, Alan F.; Pirow, Ralph; Andra, Syam S.; Church, Rebecca; Nachman, Rebecca; Linke, Susanne; Kapraun, Dustin F.; Schurman, Shepherd H.; Arora, Manish; Thayer, Kristina A.; Bucher, John R.; Birnbaum, Linda S.

doi:10.1016/j.envint.2020.106031

Cited by 35 publications

(9 citation statements)

References 31 publications

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“…Notably, a majority of PFASs retained in the skin layers (54.1–80.1% in the L group and 45.9–69.1% in the H group) were found in the stratum corneum (Figures c and S2). Because only PFASs stored in the viable epidermis and dermis may eventually reach the blood, and are thus considered systemically accessible, , our observations suggest that the stratum corneum acts as the first biological barrier to the penetration of PFASs into the systemic circulation. In addition, the penetration of PFASs through the stratum corneum was increased in the H group, especially for long-chain PFASs.…”

Section: Resultsmentioning

confidence: 88%

Insights into the Dermal Absorption, Deposition, and Elimination of Poly- and Perfluoroalkyl Substances in Rats: The Importance of Skin Exposure

Chen

et al. 2022

Environ. Sci. Technol.

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Humans are frequently exposed to poly- and perfluoroalkyl substances (PFASs) via direct skin contact with personal care and consumer products containing them. Here, we used a rat model to estimate the dermal penetration efficiency of 15 representative PFASs. After 144 h post-dosing, 4.1–18.0 and 5.3–15.1% of the applied PFASs in the low (L) and high (H) groups, respectively, were absorbed into the rats. PFAS absorption and permeation were parabolically associated with the perfluorinated carbon chain length (C F), peaking for perfluoroheptanoic acid (PFHpA). The lipid-rich stratum corneum of the skin barrier substantially suppressed the penetration of less hydrophobic short-chain PFASs, whereas the water-rich viable epidermis and dermis served as obstacles to hydrophobic long-chain PFAS permeation. However, the renal clearance (CLrenal) of the target PFAS decreased with increasing C F, suggesting that urinary excretion is crucial to eliminate less hydrophobic short-chain PFASs. Notably, the peak times of PFASs in the systemic circulation of rats (8–72 h) were remarkably longer than those after oral administration (1–24 h). These results suggest that dermal penetration can be long-lasting and contribute considerably to the body burden of PFASs, especially for those with moderate hydrophobicity due to their favorable skin permeation and unfavorable urinary excretion.

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Section: Resultsmentioning

confidence: 88%

Insights into the Dermal Absorption, Deposition, and Elimination of Poly- and Perfluoroalkyl Substances in Rats: The Importance of Skin Exposure

Chen

et al. 2022

Environ. Sci. Technol.

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“…Every oral human pharmacokinetic study has shown that the half-life of total BPA (free and conjugated) in adult humans is approximately 6 h ( Volkel et al, 2002 ; Thayer et al, 2015 ) and nearly 100% is eliminated through the urine within 24 h ( Volkel et al, 2002 ; Volkel et al, 2005 ; Teeguarden et al, 2015 ; Thayer et al, 2015 ). More recently, Sasso et al (2020) found the half-life of BPA via dermal exposure was slightly longer at approximately 20 h. Because humans can metabolize BPA rapidly, it is speculated that the high human exposure estimates (i.e., within the ng/ml range) may be erroneous, due to BPA contamination from the laboratory plastics used to collect, store, and process biological samples ( Doerge et al, 2011 ; Vandenberg et al, 2013 ). Although plastic contamination is a potential issue that could artificially inflate exposure estimates, an analysis of CDC data from the National Health and Nutrition Examination Survey proposed that the half-life of BPA may be longer than expected, and humans are ubiquitously exposed via multiple routes ( Stahlhut et al, 2009 ).…”

Section: Contaminants Of Immediate and Emerging Concern That May Cros...mentioning

confidence: 99%

The development and function of the brain barriers – an overlooked consideration for chemical toxicity

Bell

O’Shaughnessy²

2022

Front. Toxicol.

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It is well known that the adult brain is protected from some infections and toxic molecules by the blood-brain and the blood-cerebrospinal fluid barriers. Contrary to the immense data collected in other fields, it is deeply entrenched in environmental toxicology that xenobiotics easily permeate the developing brain because these barriers are either absent or non-functional in the fetus and newborn. Here we review the cellular and physiological makeup of the brain barrier systems in multiple species, and discuss decades of experiments that show they possess functionality during embryogenesis. We next present case studies of two chemical classes, perfluoroalkyl substances (PFAS) and bisphenols, and discuss their potential to bypass the brain barriers. While there is evidence to suggest these pollutants may enter the developing and/or adult brain parenchyma, many studies suffer from confounding technical variables which complicates data interpretation. In the future, a more formal consideration of brain barrier biology could not only improve understanding of chemical toxicokinetics but could assist in prioritizing environmental xenobiotics for their neurotoxicity risk.

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“…In the general population, approximately 1 μg of BPA is transferred per 1 finger after holding thermal paper for 5 s, with wet or greasy fingers increasing it to 23 μg per finger ( Biedermann et al, 2010 ). In the study of Sasso et al (2020) , the half-life of free d6-BPA after dermal contact was determined to be up to 17.6 h, which is three times longer than after oral administration. Bisphenols that enter the body after dermal contact are excreted more slowly.…”

Section: Exposure Routes Of Endocrine Disruptorsmentioning

confidence: 99%

Overview of the Mechanisms of Action of Selected Bisphenols and Perfluoroalkyl Chemicals on the Male Reproductive Axes

et al. 2021

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Male fertility has been deteriorating worldwide for considerable time, with the greatest deterioration recorded mainly in the United States, Europe countries, and Australia. That is, especially in countries where an abundance of chemicals called endocrine disruptors has repeatedly been reported, both in the environment and in human matrices. Human exposure to persistent and non-persistent chemicals is ubiquitous and associated with endocrine-disrupting effects. This group of endocrine disrupting chemicals (EDC) can act as agonists or antagonists of hormone receptors and can thus significantly affect a number of physiological processes. It can even negatively affect human reproduction with an impact on the development of gonads and gametogenesis, fertilization, and the subsequent development of embryos. The negative effects of endocrine disruptors on sperm gametogenesis and male fertility in general have been investigated and repeatedly demonstrated in experimental and epidemiological studies. Male reproduction is affected by endocrine disruptors via their effect on testicular development, impact on estrogen and androgen receptors, potential epigenetic effect, production of reactive oxygen species or direct effect on spermatozoa and other cells of testicular tissue. Emerging scientific evidence suggests that the increasing incidence of male infertility is associated with the exposure to persistent and non-persistent endocrine-disrupting chemicals such as bisphenols and perfluoroalkyl chemicals (PFAS). These chemicals may impact men’s fertility through various mechanisms. This study provides an overview of the mechanisms of action common to persistent (PFAS) and nonpersistent (bisphenols) EDC on male fertility.

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Pharmacokinetics of bisphenol A in humans following dermal administration

Cited by 35 publications

References 31 publications

Insights into the Dermal Absorption, Deposition, and Elimination of Poly- and Perfluoroalkyl Substances in Rats: The Importance of Skin Exposure

Insights into the Dermal Absorption, Deposition, and Elimination of Poly- and Perfluoroalkyl Substances in Rats: The Importance of Skin Exposure

The development and function of the brain barriers – an overlooked consideration for chemical toxicity

Overview of the Mechanisms of Action of Selected Bisphenols and Perfluoroalkyl Chemicals on the Male Reproductive Axes

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