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Environmental Health Perspectives Nov 2022
Topics: Alkanesulfonic Acids; Fluorocarbons; Alkanesulfonates
PubMed: 36331817
DOI: 10.1289/EHP12012 -
Environmental Health Perspectives Jun 2019Bisphenol S (BPS) has been widely substituted for bisphenol A (BPA) on thermal papers, but little is known about its skin absorption.
BACKGROUND
Bisphenol S (BPS) has been widely substituted for bisphenol A (BPA) on thermal papers, but little is known about its skin absorption.
OBJECTIVES
We compared the percutaneous absorption and biotransformation of BPS and BPA in vitro and in a controlled human trial.
METHODS
Absorption and biotransformation of BPS and BPA were monitored across reconstructed human epidermis at two environmentally relevant doses over 25 h. In the human trial, five male participants handled thermal receipts containing BPS and washed their hands after 2 h. Urine (0-48 h) and serum (0-7.5h) were analyzed for target bisphenols, and one participant repeated the experiment with extended monitoring. BPS data were compared with published data for isotope-labeled BPA ([Formula: see text]) in the same participants.
RESULTS
At doses of 1.5 and [Formula: see text] applied to reconstructed human epidermis, the permeability coefficient of BPS (0.009 and [Formula: see text], respectively) was significantly lower than for BPA (0.036 and [Formula: see text], respectively), and metabolism of both bisphenols was negligible. In participants handling thermal receipts, the quantities of BPS and [Formula: see text] on hands was significantly correlated with maximum urinary event flux ([Formula: see text]), but the slope was lower for BPS than BPA ([Formula: see text] and 1.1, respectively). As a proportion of total urinary bisphenol, free BPS [[Formula: see text]: [Formula: see text]] was higher than for free BPA ([Formula: see text]). Postexposure maximum urinary BPS concentrations (0.93 to [Formula: see text]; [Formula: see text]) were in the 93-98th percentile range of BPS in background Canadians ([Formula: see text]; [Formula: see text]).
CONCLUSION
Both the in vitro and human studies suggested lower percutaneous absorption of BPS compared with BPA, but a lower biotransformation efficiency of BPS should also be considered in its evaluation as a BPA substitute. https://doi.org/10.1289/EHP5044.
Topics: Benzhydryl Compounds; Epidermis; Hand; Humans; Male; Organ Culture Techniques; Paper; Phenols; Skin Absorption; Sulfones
PubMed: 31199677
DOI: 10.1289/EHP5044 -
Ecotoxicology and Environmental Safety Jun 2021Bisphenol A (BPA) is a ubiquitous industrial chemical found in everyday plastic products and materials. Due to scientific findings on the reproductive, developmental,...
Bisphenol A (BPA) is a ubiquitous industrial chemical found in everyday plastic products and materials. Due to scientific findings on the reproductive, developmental, and cellular defects caused by BPA and heightened public awareness, manufacturers have begun to use new chemicals in place of BPA in "BPA-free" products. These alternatives are chemical analogs of BPA and include dozens of new compounds that have undergone relatively little testing and oversight, including: bisphenol S (BPS), bisphenol AF (BPAF), and the recently developed tetramethyl bisphenol F (TMBPF; the monomer of valPure V70). Here, we used adult female rat adipose-derived stem cells (rASCs) and human mesenchymal stem cells (hMSCs) to compare the toxicities and potencies of these BPA alternatives in vitro. Rat and human stem cells were exposed to BPA (1-10 μM), 17β-estradiol (E2; 10 μM), BPS (1-100 μM), BPAF (3×10-30 μM), TMBPF (0.01-50 μM), or control media alone (with 0.01% ethanol) for varying time intervals from 10 min to 24 h. We found significantly decreased cell viability and massive apoptosis in rat and human stem cells treated with each BPA analog, as early as 10 min of exposure, and at low, physiologically relevant doses. BPAF showed extreme cytotoxicity in a dose-dependent manner (LC =0.014 μM (rASCs) and 0.009 μM (hMSCs)), whereas TMBPF showed a bimodal response, with low and high concentrations being the most toxic (LC =0.88 μM (rASCs) and 0.06 μM (hMSCs)). Activated caspase-6 levels increased in nearly all cells treated with the BPA analogs indicating the majority of cell death was due to caspase-6-mediated apoptosis. These results in both rat and human stem cells underscore the toxicity and potency of these BPA analogs, and establish a rank order of potency of: BPAF>TMBPF>BPA>BPS. Further, these and other recent findings indicate that these newer BPA analogs may be 'regrettable substitutions,' being worse than the original parent compound and lacking proper testing and regulation. This work brings to light the need for further toxicological characterization, better regulation, greater public awareness, and the development of safer, more sustainable chemicals and non-plastic products.
Topics: Animals; Apoptosis; Benzhydryl Compounds; Cell Survival; Environmental Pollutants; Estradiol; Female; Humans; Phenols; Rats; Stem Cells; Sulfones; Toxicity Tests
PubMed: 33866271
DOI: 10.1016/j.ecoenv.2021.112210 -
Environmental Health Perspectives Jul 2023Nontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.
BACKGROUND
Nontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.
OBJECTIVES
We characterized levels of nine exogenous and endogenous chemicals in maternal and cord blood identified, selected, and confirmed in prior NTA steps, including linear and branched isomers perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), monoethylhexyl phthalate, 4-nitrophenol, tetraethylene glycol, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid. We evaluated relationships between maternal and cord levels and between gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy in a diverse pregnancy cohort in San Francisco.
METHODS
We collected matched maternal and cord serum samples at delivery from 302 pregnant study participants from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculated distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used adjusted logistic regression to calculate the odds of GDM and hypertensive disorders of pregnancy associated with an interquartile range increase in maternal chemical exposures.
RESULTS
We detected linear PFOS, PFHxS, octadecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. Correlations ranged between and 0.9. We observed strong correlations between cord and maternal levels of PFHxS, linear PFOS, and branched PFOS (, 0.8, and 0.8, respectively). An interquartile range increase in linear and branched PFOS, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid was associated with increased odds ratio (OR) of GDM [ (95% CI: 0.89, 2.01), 1.24 (95% CI: 0.86, 1.80), 1.26 (95% CI: 0.93, 1.73), 1.24 (95% CI: 0.86, 1.80), and 1.23 (95% CI: 0.87, 1.75), respectively]. Tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [ (95% CI: 0.90, 1.86)].
DISCUSSION
We identified both exogenous and endogenous chemicals seldom quantified in pregnant study participants that were also related to pregnancy complications and demonstrated the utility of NTA to identify chemical exposures of concern. https://doi.org/10.1289/EHP11546.
Topics: Pregnancy; Female; Humans; Cross-Sectional Studies; Cohort Studies; Hypertension, Pregnancy-Induced; Pregnancy Complications; Diabetes, Gestational; Alkanesulfonic Acids; Alkanesulfonates; Fluorocarbons; Deoxycholic Acid; Environmental Pollutants
PubMed: 37466315
DOI: 10.1289/EHP11546 -
Environmental and Molecular Mutagenesis Jul 2022Bisphenol A (BPA), a recognized endocrine-disrupting chemical, is used in the production of epoxy and polycarbonate resins. Since human exposure to BPA has been...
Bisphenol A (BPA), a recognized endocrine-disrupting chemical, is used in the production of epoxy and polycarbonate resins. Since human exposure to BPA has been associated with increased cancer susceptibility, the market has shifted to products often labeled as "BPA free" containing BPA analogs such as bisphenol F (BPF) and bisphenol S (BPS). However, the European legislation on BPF and BPS is still unclear. This study analyzed the effects of BPA, BPF, and BPS exposure on human peripheral blood mononuclear cells by using in vitro micronucleus assay. Furthermore, it investigated the impact of bisphenols exposure on human endogenous retroviruses (HERVs) expression, which is implicated with the pathogenesis of several human diseases. The micronucleus assay revealed a significant genotoxic effect in peripheral blood cells after exposure to BPA and BPF at concentrations of 0.1, 0.05, and 0.025 μg/ml, and to BPS at 0.1 and 0.05 μg/ml. In addition, BPA exposure seems to upregulate the expression of HERVs, while a downregulation was observed after BPF and BPS treatments. Overall, our data showed the toxic effect of BPA and its analogs on circulating cells in the blood and demonstrated that they could modulate the HERVs expression.
Topics: Benzhydryl Compounds; Endogenous Retroviruses; Genomics; Humans; Leukocytes, Mononuclear; Phenols; Sulfones
PubMed: 36054626
DOI: 10.1002/em.22499 -
Environment International Feb 2023Epidemiologic studies of serum per- and polyfluoroalkyl substances (PFAS) and antibody response to vaccines have suggested an adverse association, but the consistency... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epidemiologic studies of serum per- and polyfluoroalkyl substances (PFAS) and antibody response to vaccines have suggested an adverse association, but the consistency and magnitude of this association remain unclear.
OBJECTIVE
The goal of this systematic review was to determine the size of the association between a doubling in perfluoroalkyl substances (PFAS) serum concentration and difference in log antibody concentration following a vaccine, with a focus on five PFAS: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA).
DATA SOURCE
We conducted online searches of PubMed and Web of Science through May 17, 2022 and identified 14 eligible reports published from 2012 to 2022.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
We included studies conducted in humans, including mother-child pairs, which examined serum PFAS concentration in relation to serum concentration of antibody to a specific antigen following a vaccine.
STUDY APPRAISAL AND SYNTHESIS METHODS
We used the risk of bias assessment for non-randomized studies of exposure and certainty assessment method proposed by Morgan et al. (2019). Using a multilevel meta-regression model, we quantitatively synthesized the data.
RESULTS
The 14 reports represented 13 unique groups of subjects; the frequency of studies of a given antibody was Tetanus (n = 7); followed by Diphtheria (6); Measles (4); Rubella (3); Haemophilus influenzae type b and Influenza A H1N1 (2 each); and Hepatitis A, Hepatitis B, Influenza A H2N3, Influenza B, and Mumps (1 each). There were approximately 4,830 unique participants included in the analyses across the 14 reports. The models of coefficients between antibody concentration and the five principal PFAS showed homogeneity of associations across antibody types for each principal PFAS. In the models with all antibodies treated as one type, evidence of effect modification by life stage was present for PFOA and PFOS, and for consistency, all associations were evaluated for all ages and for children. The summary associations (coefficients for difference in log[antibody concentration] per doubling of serum PFAS) with 95% confidence intervals that excluded zero ("statistical support"), and certainty of evidence ratings were as follows: for PFOA and all antibodies treated as one type in all ages, -0.06 (-0.10, -0.01; moderate) and in children, -0.10 (-0.16, -0.03; moderate); for Diphtheria in children, -0.12 (-0.23, -0.00; high); for Rubella in all ages, -0.09 (-0.17, -0.01; moderate), and for Tetanus in children, -0.12 (-0.24, -0.00; moderate). For PFOS the summary associations were, for all antibodies treated as one type in all ages, -0.06 (-0.11, -0.01; moderate) and in children, -0.10 (-0.18, -0.03; moderate); for Rubella in all ages, -0.09 (-0.15, -0.03; high) and in children, -0.12 (-0.20, -0.04; high). For PFHxS the summary associations were, for all antibodies treated as one type in all ages, -0.03 (-0.06, -0.00; moderate) and in children, -0.05 (-0.09, -0.00; low); and for Rubella in children, -0.07 (-0.11, -0.02; high). Summary associations for PFNA and PFDA did not have statistical support, but all PFAS studied tended to have an inverse association with antibody concentrations.
LIMITATIONS AND CONCLUSIONS
Epidemiologic data on immunosuppression and five principal PFAS suggest an association, with support across antibodies against multiple types of antigens. Data on Diphtheria, Rubella, and Tetanus were more supportive of an association than for other antibodies, and support was greater for associations with PFOA, PFOS, and PFHxS, than for PFNA or PFDA. The data on any specific antibody were scarce. Confounding factors that might account for the relation were not identified. Nearly all studies evaluated were judged to have a low or moderate risk of bias.
Topics: Humans; Infant, Newborn; Infant; Environmental Pollutants; Tetanus; Diphtheria; Influenza A Virus, H1N1 Subtype; Influenza, Human; Fluorocarbons; Vaccines; Alkanesulfonic Acids; Alkanesulfonates; Rubella
PubMed: 36764183
DOI: 10.1016/j.envint.2023.107734 -
Molecules (Basel, Switzerland) May 2023Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the...
Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the factors responsible for the distribution of sulfonamides in the living organism. Although these drug compounds have been in use for more than half a century, knowledge about their behavior is still limited. Physiological activity is currently attributed to the sulfanyl radical. Our study is devoted to the spectral properties of aqueous solutions of sulfaguanidine, in which the formation of complexes with an H-bond and a protonated form takes place. The nature of the fluorescent state of sulfaguanidine was interpreted using computational chemistry, the electronic absorption method and the luminescence method. The structure of sulfaguanidine includes several active fragments: aniline, sulfonic and guanidine. To reveal the role of fragments in the physiological activity of the studied antibiotic, we calculated and compared the effective charges of the fragments of aniline and sulfaguanidine molecules. Chromophore groups were identified in molecules, which determine the intermolecular interaction between a molecule and a proton-donor solvent. The study also revealed the impact of sulfone and guanidine groups, as well as complexation, on the effective charge of the antibiotic fragment responsible for physiological activity and luminescent ability.
Topics: Sulfaguanidine; Luminescence; Anti-Bacterial Agents; Sulfonamides; Sulfanilamide; Aniline Compounds; Guanidines
PubMed: 37241901
DOI: 10.3390/molecules28104159 -
Current Topics in Medicinal Chemistry 2016The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a... (Review)
Review
The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented.
Topics: Chemistry, Pharmaceutical; Drug Discovery; Humans; Penicillins; Sulfides; Sulfonamides; Sulfones; Sulfur Compounds
PubMed: 26369815
DOI: 10.2174/1568026615666150915111741 -
Nature Communications Sep 2020Natural biomolecules such as peptides and DNA can dynamically self-organize into diverse hierarchical structures. Mimicry of this homopolymer self-assembly using...
Natural biomolecules such as peptides and DNA can dynamically self-organize into diverse hierarchical structures. Mimicry of this homopolymer self-assembly using synthetic systems has remained limited but would be advantageous for the design of adaptive bio/nanomaterials. Here, we report both experiments and simulations on the dynamic network self-assembly and subsequent collapse of the synthetic homopolymer poly(propylene sulfone). The assembly is directed by dynamic noncovalent sulfone-sulfone bonds that are susceptible to solvent polarity. The hydration history, specified by the stepwise increase in water ratio within lower polarity water-miscible solvents like dimethylsulfoxide, controls the homopolymer assembly into crystalline frameworks or uniform nanostructured hydrogels of spherical, vesicular, or cylindrical morphologies. These electrostatic hydrogels have a high affinity for a wide range of organic solutes, achieving >95% encapsulation efficiency for hydrophilic small molecules and biologics. This system validates sulfone-sulfone bonding for dynamic self-assembly, presenting a robust platform for controllable gelation, nanofabrication, and molecular encapsulation.
Topics: Alkenes; Hydrogels; Hydrophobic and Hydrophilic Interactions; Polypropylenes; Static Electricity; Sulfones
PubMed: 32994414
DOI: 10.1038/s41467-020-18657-5 -
Bioconjugate Chemistry Jan 2018The attachment of two different functionalities in a site-selective fashion represents a great challenge in protein chemistry. We report site specific dual...
The attachment of two different functionalities in a site-selective fashion represents a great challenge in protein chemistry. We report site specific dual functionalizations of peptides and proteins capitalizing on reactivity differences of cysteines in their free (thiol) and protected, oxidized (disulfide) forms. The dual functionalization of interleukin 2 and EYFP proceeded with no loss of bioactivity in a stepwise fashion applying maleimide and disulfide rebridging allyl-sulfone groups. In order to ensure broader applicability of the functionalization strategy, a novel, short peptide sequence that introduces a disulfide bridge was designed and site-selective dual labeling in the presence of biogenic groups was successfully demonstrated.
Topics: Allyl Compounds; Animals; Bacterial Proteins; Cell Line; Cysteine; Humans; Interleukin-2; Luminescent Proteins; Maleimides; Mice; Models, Molecular; Peptides; Proteins; Recombinant Proteins; Staining and Labeling; Sulfhydryl Compounds; Sulfones
PubMed: 29231709
DOI: 10.1021/acs.bioconjchem.7b00675