In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths

Perfluoroalkyl carboxylic acids (PFCAs), such as perfluorooctanoic acid (PFOA, C8), are a group of industrial chemicals that are detected in the serum of people throughout the world. Long-chain PFCAs (C9 to C13) have high lipophilicity, therefore they may have a high transfer rate to breast milk. This study investigated the lactational transfer of PFCAs with carbon chain lengths of 8 to 13 in mice. Lactating dams were given a single intravenous administration of PFCAs (C8 to C13) during the postnatal period (8–13 days after delivery). Milk was collected from the dam 24 h after administration using a milking device built in-house. Plasma was obtained from the dam at the same time as milk collection. The observed milk/plasma (M/P) concentration ratios were 0.32 for C8, 0.30 for C9, 0.17 for C10, 0.21 for C11, 0.32 for C12, and 0.49 for C13. These results indicate that the M/P concentration ratio is not related to the lipophilicity of PFCAs. However, estimated relative daily intake, an indicator of how much PFCA is transferred from dams to pups per body weight, increased with chain length: 4.16 for C8, 8.98 for C9, 9.35 for C10, 9.51 for C11, 10.20 for C12, and 10.49 for C13, which may be related to the lower clearance of long-chain PFCAs. These results indicate the importance of future risk assessment of long-chain PFCAs.

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Subacute dermal toxicity of perfluoroalkyl carboxylic acids: comparison with different carbon-chain lengths in human skin equivalents and systemic effects of perfluoroheptanoic acid in Sprague Dawley rats

Archives of Toxicology ◽

10.1007/s00204-019-02634-z ◽

2019 ◽

Vol 94 (2) ◽

pp. 523-539 ◽

Cited By ~ 3

Author(s):

Ji-Seok Han ◽

Sumi Jang ◽

Hwa-Young Son ◽

Yong-Bum Kim ◽

Younhee Kim ◽

...

Keyword(s):

Carboxylic Acids ◽

Human Skin ◽

Carbon Chain ◽

Systemic Effects ◽

Sprague Dawley ◽

Dermal Toxicity ◽

Skin Equivalents ◽

Sprague Dawley Rats ◽

Chain Lengths

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Synthesis and Characterization of Novel Copolymeric Resveratrol Conjugates

Journal of Chemistry ◽

10.1155/2015/245625 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Yan-Jing Ng ◽

Heather A. E. Benson ◽

David H. Brown ◽

Yan Chen

Keyword(s):

Micelle Formation ◽

Rat Plasma ◽

The Body ◽

Poly Ethylene Glycol ◽

Poly Ethylene ◽

The Stability ◽

Chain Lengths ◽

Cardioprotective Drug

Resveratrol (RSV), naturally found in plants, is known to have health benefits and has been proposed as a potential anticancer and cardioprotective drug. However, due to its molecular structure, it undergoes rapid metabolism in the body resulting in low bioavailability. Novel polymeric methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) RSV conjugates with varying PCL chain lengths have been synthesised and formulated into micelles and/or nanoparticles for preliminaryin vitrostability studies. RSV conjugated with mPEG2000-PCL9500 was found to have improved solubility and stability of RSV as compared to RSV alone. The length of the PCL chain was found to affect the micelle formation, hence the stability in physiological buffers and rat plasma.

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Toxicity of perfluorinated carboxylic acids for aquatic organisms

Interdisciplinary Toxicology ◽

10.2478/v10102-010-0014-2 ◽

2010 ◽

Vol 3 (2) ◽

pp. 73-75 ◽

Cited By ~ 2

Author(s):

Miloň Tichý ◽

Radka Valigurová ◽

Radomír Čabala ◽

Rut Uzlová ◽

Marián Rucki

Keyword(s):

Standard Deviation ◽

Acute Toxicity ◽

Aqueous Solutions ◽

Carboxylic Acids ◽

Aquatic Organisms ◽

Carbon Chain ◽

Tubifex Tubifex ◽

Large Standard Deviation ◽

Significant Difference ◽

Perfluorinated Carboxylic Acids

Toxicity of perfluorinated carboxylic acids for aquatic organismsToxicity of perfluorinated carboxylic acids with carbon chain C8to C12were tested with oligochaetaTubifex tubifex.Toxicity was evaluated as the exposure time ET50from onset of damage of the oligochaeta in saturated aqueous solutions. The ET50fluctuated between 25 and 257 minutes. No statistically significant difference was found among the C8, C9and C12acids (ET50between 143 and 257 minutes with large standard deviation). The acids with carbon chain C10and C11induced the effect significantly quicker (25 to 47 minutes). No acute toxicity measured in the three-minute test was observed in any case.

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Predicting the Effects of Per- and Polyfluoroalkyl Substance Mixtures on Peroxisome Proliferator-Activated Receptor Alpha Activity in Vitro

10.1101/2021.09.30.462638 ◽

2021 ◽

Author(s):

Greylin Nielsen ◽

Wendy J. Heiger-Bernays ◽

Jennifer J. Schlezinger ◽

Thomas F. Webster

Keyword(s):

Carboxylic Acids ◽

Receptor Activity ◽

Luciferase Reporter ◽

Peroxisome Proliferator ◽

Sulfonic Acids ◽

Peroxisome Proliferator Activated Receptor ◽

Full Agonist ◽

Partial Agonists ◽

Perfluorinated Carboxylic Acids

AbstractHuman exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous, with mixtures of PFAS detected in drinking water, food, household dust, and other exposure sources. Animal toxicity studies and human epidemiology indicate that PFAS may act through shared mechanisms including activation of peroxisome proliferator activated receptor α (PPARα). However, the effect of PFAS mixtures on human relevant molecular initiating events remains an important data gap in the PFAS literature. Here, we tested the ability of modeling approaches to predict the effect of diverse PPARα ligands on receptor activity using Cos7 cells transiently transfected with a full length human PPARα (hPPARα) expression construct and a peroxisome proliferator response element-driven luciferase reporter. Cells were treated for 24 hours with two full hPPARα agonists (pemafibrate and GW7647), a full and a partial hPPARα agonist (pemafibrate and mono(2-ethylhexyl) phthalate), or a full hPPARα agonist and a competitive antagonist (pemafibrate and GW6471). Receptor activity was modeled with three additive approaches: effect summation, relative potency factors (RPF), and generalized concentration addition (GCA). While RPF and GCA accurately predicted activity for mixtures of full hPPARα agonists, only GCA predicted activity for full and partial hPPARα agonists and a full agonist and antagonist. We then generated concentration response curves for seven PFAS, which were well-fit with three-parameter Hill functions. The four perfluorinated carboxylic acids (PFCA) tended to act as full hPPARα agonists while the three perfluorinated sulfonic acids (PFSA) tended to act as partial agonists that varied in efficacy between 28-67% of the full agonist, positive control level. GCA and RPF performed equally well at predicting the effects of mixtures with three PFCAs, but only GCA predicted experimental activity with mixtures of PFSAs and a mixture of PFCAs and PFSAs at ratios found in the general population. We conclude that of the three approaches, GCA most accurately models the effect of PFAS mixtures on hPPARα activity in vitro.HighlightsPerfluorinated carboxylic acids are full human PPARα agonistsPerfluorinated sulfonic acids are partial human PPARα agonistsGCA predicts human PPARα activity for mixtures of full and partial agonistsGCA predicts human PPARα activity for mixtures of agonists and competitive antagonistsGCA accurately predicts human PPARα activity in response to PFAS mixtures

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Morphology, Ionic-Molecular Interaction and Ionic Conductivity Behavior of PMMA/ENR 50 Electrolytes Containing Carboxylic Acids Modified SiO2 Fillers

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.821.419 ◽

2019 ◽

Vol 821 ◽

pp. 419-425

Author(s):

Mohamad Zamri Sharil Fadli ◽

Abdul Latif Famiza ◽

Mohd Azuan Siti Izzati Husna

Keyword(s):

Ionic Conductivity ◽

Carboxylic Acids ◽

Octanoic Acid ◽

Silanol Group ◽

Carbon Chain ◽

Dodecanoic Acid ◽

Casting Method ◽

Acid Modification ◽

Lithium Tetrafluoroborate ◽

Chain Lengths

Carboxylic acids of various carbon chain lengths (Cn); i.e. butanoic acid (C4), octanoic acid (C8), dodecanoic acid (C12) and hexadecanoic acid (C16) have been used to organically modify silicon dioxide (SiO2). The acid modification involve replacing the hydrogen atom of the silanol group (Si-OH) of SiO2 with the RnCOO-of the acid via esterification technique. SiO2 and acid modified SiO2 (MoCn-SiO2) were used as filler in preparation of polymethyl methacrylate/50% epoxidized natural rubber electrolytes containing SiO2 (PEL-SiO2) and MoCn-SiO2 (PEL-MoCn-SiO2) via solvent casting method with lithium tetrafluoroborate (LiBF4) as dopant salt. Field-emission scanning electron microscopy (FESEM) analysis of PEL-SiO2 and PEL-MoCn-SiO2 films show LiBF4 accumulated to the fillers. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed formation of hydrogen bonding between LiBF4 with fillers and polymers in the polymer electrolyte films. Interestingly, the ionic conductivity of PEL-MoCn-SiO2 films increases as the Cn of acids increased with the highest ionic conductivity of 5.56 x 10-7 Scm-1 was achieved in PEL-MoC12-SiO2 film.

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Evaluation of Single and Joint Toxicity of Perfluorinated Carboxylic Acids and Copper to Metal-Resistant Arthrobacter Strains

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16010135 ◽

2019 ◽

Vol 16 (1) ◽

pp. 135 ◽

Cited By ~ 1

Author(s):

Yanping Cai ◽

Haiyan Chen ◽

Huilun Chen ◽

Haiqing Li ◽

Shuo Yang ◽

...

Keyword(s):

Chain Length ◽

Carbon Chain ◽

Growth Rate Constant ◽

Carbon Chain Length ◽

Natural Environments ◽

Joint Toxicity ◽

Perfluorinated Carboxylic Acids ◽

Arthrobacter Strain ◽

Series Of Experiments ◽

Chain Lengths

Perfluorocarboxylic acid compounds (PFCAs) and copper have been regarded as ubiquitous environmental contaminants in aquatic ecosystems worldwide. However, data on their possible joint toxic effects on microorganisms are still lacking. To study the combined effects of four PFCAs with different carbon chain lengths and copper, a series of experiments were conducted to explore the acute toxicity of these PFCAs in the absence and presence of copper on a metal-resistant Arthrobacter strain GQ-9 by microcalorimetry. The thermokinetic parameters, including growth rate constant (k), inhibitory ratio (I), and half inhibitory concentration (IC50), were calculated and compared using the data obtained from the power-time curves. Our work revealed that GQ-9 is more resistant to perfluorooctanoic acid (PFOA) than Escherichia coli. The single and joint toxicity of PFCAs with copper are dose- and carbon chain length-dependent. The longer the carbon chain length of PFCAs, the higher the toxicity. In addition, PFCAs interacted synergistically with copper. This work could provide useful information for the risk assessment of co-exposure to perfluorinated compounds and heavy metals in natural environments.

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Characterization of complexes formed between debranched starch and fatty acids having different carbon chain lengths

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2020.11.198 ◽

2021 ◽

Vol 167 ◽

pp. 595-604

Author(s):

Hao Lu ◽

Zhen Yang ◽

Mengting Yu ◽

Na Ji ◽

Lei Dai ◽

...

Keyword(s):

Fatty Acids ◽

Carbon Chain ◽

Chain Lengths

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Analysis of structure–cytotoxicity in vitro relationship (SAR) for perfluorinated carboxylic acids

Toxicology in Vitro ◽

10.1016/j.tiv.2007.04.020 ◽

2007 ◽

Vol 21 (6) ◽

pp. 1206-1211 ◽

Cited By ~ 61

Author(s):

Konrad Kleszczyński ◽

Paweł Gardzielewski ◽

Ewa Mulkiewicz ◽

Piotr Stepnowski ◽

Andrzej C. Składanowski

Keyword(s):

Carboxylic Acids ◽

Perfluorinated Carboxylic Acids

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Comprehensive Characterization of Toxicity of Fermentative Metabolites on Microbial Growth

10.1101/169482 ◽

2017 ◽

Author(s):

Brandon Wilbanks ◽

Cong T. Trinh

Keyword(s):

Energy Density ◽

Carboxylic Acids ◽

Microbial Growth ◽

Carbon Chain ◽

Toxic Effects ◽

Alkyl Esters ◽

E Coli ◽

Metabolite Concentrations ◽

Comprehensive Characterization

ABSTRACTBackgroundVolatile carboxylic acids, alcohols, and esters are natural fermentative products, typically derived from anaerobic digestion. These metabolites have important functional roles to regulate cellular metabolisms and broad use as food supplements, flavors and fragrances, solvents, and fuels. Comprehensive characterization of toxic effects of these metabolites on microbial growth under similar conditions is very limited.ResultsWe characterized a comprehensive list of 32 short-chain carboxylic acids, alcohols, and esters on microbial growth ofEscherichia coliMG1655 under anaerobic conditions. We analyzed toxic effects of these metabolites onE. colihealth, quantified by growth rate and cell mass, as a function of metabolite types, concentrations, and physiochemical properties including carbon chain lengths and associated functional groups, chain branching features, hydrophobicity, and energy density. Strain characterization reveals these metabolites exerted distinct toxic effects onE. colihealth. We find that higher concentrations and/or longer carbon lengths of metabolites cause more severe growth inhibition. For the same carbon lengths and metabolite concentrations, alcohols are most toxic followed by acids then esters. We also discover that branched chain metabolites are less toxic than linear chain metabolites for the same carbon lengths and metabolite concentrations. Remarkably, shorter alkyl esters (e.g., ethyl butyrate) are found to be less toxic than longer alkyl esters (e.g., butyl acetate) for the same carbon lengths and metabolite concentrations. Regardless of metabolite types, longer chain metabolites are less soluble and have higher energy densities but are more toxic to microbial growth.ConclusionsMetabolite hydrophobicity, correlated with carbon chain length, associated functional group, chain branching feature, and energy density, is a good quantitative index to evaluate toxic effect of a metabolite on microbial health. The results provide better understanding of degrees of toxicity of fermentative metabolites on microbial growth and further help selection of desirable metabolites and hosts for industrial fermentation to overproduce them.

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