Publications by authors named "Timothy D Phillips"

69 Publications

Testing an Iron Oxide Nanoparticle-Based Method for Magnetic Separation of Nanoplastics and Microplastics from Water.

Nanomaterials (Basel) 2022 Jul 9;12(14). Epub 2022 Jul 9.

Department of Life Sciences, Texas A&M University, Corpus Christi, TX 78412, USA.

Nanoplastic pollution is increasing worldwide and poses a threat to humans, animals, and ecological systems. High-throughput, reliable methods for the isolation and separation of NMPs from drinking water, wastewater, or environmental bodies of water are of interest. We investigated iron oxide nanoparticles (IONPs) with hydrophobic coatings to magnetize plastic particulate waste for removal. We produced and tested IONPs synthesized using air-free conditions and in atmospheric air, coated with several polydimethylsiloxane (PDMS)-based hydrophobic coatings. Particles were characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), superconducting quantum interference device (SQUID) magnetometry, dynamic light scattering (DLS), X-ray diffraction (XRD) and zeta potential. The IONPs synthesized in air contained a higher percentage of the magnetic spinel phase and stronger magnetization. Binding and recovery of NMPs from both salt and freshwater samples was demonstrated. Specifically, we were able to remove 100% of particles in a range of sizes, from 2-5 mm, and nearly 90% of nanoplastic particles with a size range from 100 nm to 1000 nm using a simple 2-inch permanent NdFeB magnet. Magnetization of NMPs using IONPs is a viable method for separation from water samples for quantification, characterization, and purification and remediation of water.
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http://dx.doi.org/10.3390/nano12142348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315505PMC
July 2022

Development and characterization of chlorophyll-amended montmorillonite clays for the adsorption and detoxification of benzene.

Water Res 2022 Aug 22;221:118788. Epub 2022 Jun 22.

Interdisciplinary Faculty of Toxicology, Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. Electronic address:

After disasters, such as forest fires and oil spills, high levels of benzene (> 1 ppm) can be detected in the water, soil, and air surrounding the disaster site, which poses a significant health risk to human, animal, and plant populations in the area. While remediation methods with activated carbons have been employed, these strategies are limited in their effectiveness due to benzene's inherent stability and limited retention to most surfaces. To address this problem, calcium and sodium montmorillonite clays were amended with a mixture of chlorophyll (a) and (b); their binding profile and ability to detoxify benzene were characterized using in vitro, in silico, and well-established ecotoxicological (ecotox) bioassay methods. The results of in vitro isothermal analyses indicated that chlorophyll-amended clays showed an improved binding profile in terms of an increased binding affinity (K = 668 vs 67), increased binding percentage (52% vs 11%), and decreased rates of desorption (28% vs 100%), compared to the parent clay. In silico simulation studies elucidated the adsorption mechanism and validated that the addition of the chlorophyll to the clays increased the adsorption of benzene through Van der Waals forces (i.e., aromatic π-π stacking and alkyl-π interactions). The sorbents were also assessed for their safety and ability to protect sensitive ecotox organisms (Lemna minor and Caenorhabditis elegans) from the toxicity of benzene. The inclusion of chlorophyll-amended clays in the culture medium significantly reduced benzene toxicity to both organisms, protecting C. elegans by 98-100% from benzene-induced mortality and enhancing the growth rates of L. minor. Isothermal analyses, in silico modeling, and independent bioassays all validated our proof of concept that benzene can be sequestered, tightly bound, and stabilized by chlorophyll-amended montmorillonite clays. These novel sorbents can be utilized during disasters and emergencies to decrease unintentional exposures from contaminated water, soil, and air.
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http://dx.doi.org/10.1016/j.watres.2022.118788DOI Listing
August 2022

Inclusion of Montmorillonite Clays in Environmental Barrier Formulations to Reduce Skin Exposure to Water-Soluble Chemicals from Polluted Water.

ACS Appl Mater Interfaces 2022 May 10. Epub 2022 May 10.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, United States.

Dermal exposures to environmental chemicals can significantly affect the morphology and integrity of skin structure, leading to enhanced and deeper penetration of toxic chemicals. This problem can be magnified during disasters where hazardous water-soluble chemicals are readily mobilized and redistributed in the environment, threatening the health of vulnerable populations at the impacted sites. To address this issue, barrier emulsion formulations (EVB) have been developed consisting of materials that are generally recognized as safe, with the inclusion of medical grade carbon or calcium and sodium montmorillonite clays (CM and SM). In this study, the adsorption efficacy of five highly toxic and commonly occurring contaminants of concern, including important hydrophilic pesticides (glyphosate, acrolein, and paraquat) and per- and polyfluoroalkyl substances were characterized. EVB showed properties such as high stability, spreadability, low rupture strength, and neutral pH that were suitable for topical application on the skin. The in vitro adsorption results indicated that EVB and EVB-SM were effective, economically feasible, and favorable barrier formulations for hazardous chemical adsorption, as supported by high binding percentage, low desorption rates for an extended period of time, and high binding affinity. A pseudo-second-order kinetic model was best fitted for the adsorption process and the Freundlich model fit the adsorption isotherms with negative enthalpy values indicating spontaneous reactions that involve physisorption. The study, with varying temperatures and pH, showed that the adsorption reaction was exothermic and persistent. The results indicated that EVB and EVB-SM can be used as effective barriers to block dermal contact from water-soluble toxic pollutants during disasters.
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http://dx.doi.org/10.1021/acsami.2c04676DOI Listing
May 2022

Montmorillonite clay-based sorbents decrease the bioavailability of per- and polyfluoroalkyl substances (PFAS) from soil and their translocation to plants.

Environ Res 2022 04 4;205:112433. Epub 2021 Dec 4.

Veterinary Integrative Biosciences Department, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77845, USA. Electronic address:

Consumption of food and water contaminated with per- and polyfluoroalkyl substances (PFAS) presents a significant risk for human exposure. There is limited data on high affinity sorbents that can be used to reduce the bioavailability of PFAS from soil and translocation to plants and garden produce. To address this need, montmorillonite clay was amended with the nutrients carnitine and choline to increase the hydrophobicity of the sorbent and the interlayer spacing. In this study, the binding of PFOA (perfluorooctanoic acid) and PFOS (perfluorooctanesulfonic acid) to parent and amended clays was characterized. Isothermal analyses were conducted at pH 7 and ambient temperature to simulate environmentally-relevant conditions. The data for all tested sorbents fit the Langmuir model indicating saturable binding sites with high capacities and affinities under neutral conditions. Amended montmorillonite clays had increased capacities for PFOA and PFOS (0.51-0.71 mol kg) compared to the parent clay (0.37-0.49 mol kg). Molecular dynamics (MD) simulations suggested that hydrophobic and electrostatic interactions at the terminal fluorinated carbon chains of PFAS compounds were major modes of surface interaction. The safety and efficacy of the clays were confirmed in a living organism (Lemna minor), where clays (at 0.1% inclusion) allowed for increased growth compared to PFOA and PFOS controls (p ≤ 0.01). Importantly, soil studies showed that 2% sorbent inclusion could significantly reduce PFAS bioavailability from soil (up to 74%). Studies in plants demonstrated that inclusion of 2% sorbent significantly reduced PFAS residues in cucumber plants (p ≤ 0.05). These results suggest that nutrient-amended clays could be included in soil to decrease PFAS bioavailability and translocation of PFAS to plants.
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http://dx.doi.org/10.1016/j.envres.2021.112433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760172PMC
April 2022

Application of Edible Montmorillonite Clays for the Adsorption and Detoxification of Microcystin.

ACS Appl Bio Mater 2021 09 31;4(9):7254-7265. Epub 2021 Aug 31.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, United States.

Exposure to microcystins (MCs) in humans and animals commonly occurs through the consumption of drinking water and food contaminated with cyanobacteria. Although studies have focused on developing water filtration treatments for MCs using activated carbon, dietary sorbents to reduce the bioavailability of MCs from the stomach and intestines have not been reported. To address this need, edible calcium and sodium montmorillonite clays were characterized for their ability to bind MC containing leucine and arginine (MC-LR) under conditions simulating the gastrointestinal tract and compared with a medical-grade activated carbon. Results of in vitro adsorption isotherms and thermodynamics showed that binding plots for MC-LR on montmorillonites fit the Langmuir model with high binding capacity, affinity, Gibbs free energy, and enthalpy. The in silico results from molecular modeling predicted that the major binding mechanisms involved electrostatics and hydrogen bonds, and that interlayers were important binding sites. The safety and detoxification efficacy of the sorbents against MC-LR were validated in a battery of living organisms, including , , and The inclusion of 0.05% and 0.1% montmorillonite clays in hydra media significantly reduced MC-LR toxicity and protected hydra by 60-80%, whereas only slight protection was shown with the heat-collapsed clay. In the assay, montmorillonites significantly enhanced the growth of lemna, as supported by the increase in frond number, surface area, chlorophyll content, and growth rate, as well as the decrease in inhibition rate. Similar results were shown in the assay, where montmorillonite clays reduced MC-LR effects on body length and brood size. All 3 bioassays confirmed dose-dependent protection from MC-LR, validated the in vitro and in silico findings, and suggested that edible montmorillonites are safe and efficacious binders for MC-LR. Moreover, their inclusion in diets during algal blooming seasons could protect vulnerable populations of humans and animals.
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http://dx.doi.org/10.1021/acsabm.1c00779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570584PMC
September 2021

Evaluation of aflatoxin and fumonisin co-exposure in urine samples from healthy volunteers in northern Mexico.

Toxicol Rep 2021 4;8:1734-1741. Epub 2021 Oct 4.

Department of Physiology, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Autonoma de Nuevo Leon, General Escobedo, NL, 66050, Mexico.

Aflatoxins (AF) and fumonisins (FB) are common contaminants of maize and have been associated with cancer, immune suppression, and growth stunting. In this work, AFM and FB were measured in urine samples of healthy volunteers from the metropolitan area of Monterrey, Mexico, while AF and FB were detected in foods collected near the sampling zone. Urine samples from 106 adults were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry and toxins in foods were measured by fluorometry. The mean value of AFM and FB was 4.3 pg/mg creatinine from 76 samples (72 %), and 50 pg/mg creatinine from 75 samples (71 %), respectively. More than half of the samples (n = 56, 53 %) had detectable levels of both AFM and FB. No differences in toxin levels were found between males and females or between age groups, but AFM and FB levels were higher (p < 0.01) when detected as a single exposure compared to co-exposed. Some significant results were found when comparing AFM and FB levels among groups of people assigned to levels of food consumption. Food samples had average concentrations of 5.3 μg/kg for AF and 800 μg/kg for FB. The results showed that co-exposure to AF and FB is common in the metropolitan area of Monterrey.
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http://dx.doi.org/10.1016/j.toxrep.2021.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515162PMC
October 2021

Combining Experimental Isotherms, Minimalistic Simulations, and a Model to Understand and Predict Chemical Adsorption onto Montmorillonite Clays.

ACS Omega 2021 Jun 26;6(22):14090-14103. Epub 2021 May 26.

Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843-3122, United States.

An attractive approach to minimize human and animal exposures to toxic environmental contaminants is the use of safe and effective sorbent materials to sequester them. Montmorillonite clays have been shown to tightly bind diverse toxic chemicals. Due to their promise as sorbents to mitigate chemical exposures, it is important to understand their function and rapidly screen and predict optimal clay-chemical combinations for further testing. We derived adsorption free-energy values for a structurally and physicochemically diverse set of toxic chemicals using experimental adsorption isotherms performed in the current and previous studies. We studied the diverse set of chemicals using minimalistic MD simulations and showed that their interaction energies with calcium montmorillonite clays calculated using simulation snapshots in combination with their net charge and their corresponding solvent's dielectric constant can be used as inputs to a minimalistic model to predict adsorption free energies in agreement with experiments. Additionally, experiments and computations were used to reveal structural and physicochemical properties associated with chemicals that can be adsorbed to calcium montmorillonite clay. These properties include positively charged groups, phosphine groups, halide-rich moieties, hydrogen bond donor/acceptors, and large, rigid structures. The combined experimental and computational approaches used in this study highlight the importance and potential applicability of analogous methods to study and design novel advanced sorbent systems in the future, broadening their applicability for environmental contaminants.
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http://dx.doi.org/10.1021/acsomega.1c00481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190805PMC
June 2021

Aflatoxin Exposure Among Mothers and Their Infants from the Western Highlands of Guatemala.

Matern Child Health J 2021 Aug 4;25(8):1316-1325. Epub 2021 May 4.

College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA.

Objectives: We examined breast milk of mothers and urine of infants before and after introduction of supplementary foods for aflatoxin M (AFM) and the association between AFM with maternal and infant diet.

Methods: A prospective cohort study was conducted among mothers and infants ages 0-6 months and 7-12 months from June-October 2014. Sociodemographic, dietary, birth, and health data were collected. A breast milk sample was collected from each mother and a urine sample from each infant at baseline (time point 1) and monthly for 2 time points thereafter; samples collected at baseline and time point 3 were tested for AFM.

Results: Almost 5% of breast milk and 15.7% of urine samples tested AFM-positive. The median AFM in breast milk was 0.020 ng/mL and in urine 0.077 ng/mg creatinine. At time point 3, infants of 5 of the 6 mothers in each group who were AFM-positive in breast milk were also AFM-positive in urine. Mothers' consumption of cooked maize/maize dough ≥ 3 days per week (OR 2.96, 95% CI = 1.19-7.34) and mothers' consumption of tamales made from maize ≥ 3 days per week (OR 0.28, 95% CI = 0.10-0.73) were significantly associated with AFM in infant urine.

Conclusion: This is the first study in Guatemala documenting aflatoxin exposure in both breast milk of lactating mothers and infants´ urine during the first year of life. This may have important implications in understanding the multicausality of the high rates of stunting among children < 5 years old in Guatemala.
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http://dx.doi.org/10.1007/s10995-021-03151-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404172PMC
August 2021

Edible clay inclusion in the diet of oysters can reduce tissue residues of polychlorinated biphenyls.

Toxicol Environ Health Sci 2020 Dec 3;12(4):355-361. Epub 2020 Jun 3.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.

Objective: Polychlorinated biphenyls (PCBs) are lipophilic and persistent environmental pollutants that are readily absorbed and accumulated in high concentrations in fatty tissues of humans and animals. Invertebrate animals, such as oysters, are vulnerable and sensitive to PCB contamination.

Methods: Previously, our in vitro isothermal studies have shown that acid processed montmorillonites (APM) can effectively bind PCBs and Aroclors. Therefore, in a novel application of this work, a dietary strategy for shellfish was developed using APM, and its parent clay to reduce exposures to PCBs in oysters. PCB residues in oysters with clay treatment at different dietary inclusion rates and durations were measured and compared to a washout treatment.

Results: The efficacy and safety of this strategy were supported by a significant reduction of PCB residues with the inclusion of a low level of APM (0.05%) during a 4-day treatment. Moreover, this sorbent strategy reduced PCB residues in oysters in a dose- and time-dependent manner.

Conclusions: Based on our results, it is possible that clay-based sorbents such as APM, can be included in the diet to significantly reduce exposures to PCBs.
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http://dx.doi.org/10.1007/s13530-020-00058-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968863PMC
December 2020

Decreased bioavailability of aminomethylphosphonic acid (AMPA) in genetically modified corn with activated carbon or calcium montmorillonite clay inclusion in soil.

J Environ Sci (China) 2021 Feb 27;100:131-143. Epub 2020 Jul 27.

Veterinary Integrative Biosciences Department College of Veterinary Medicine and Biomedical Sciences, Texas A&M University College Station, TX 77845, USA. Electronic address:

The widespread use of pesticides has resulted in detectable residues throughout the environment, sometimes at concentrations well above regulatory limits. Therefore, the development of safe, effective, field-practical, and economically feasible strategies to mitigate the effects of pesticides is warranted. Glyphosate is an organophosphorus herbicide that is degraded to aminomethylphosphonic acid (AMPA), a toxic and persistent metabolite that can accumulate in soil and sediment and translocate to plants. In this study, we investigated the binding efficacy of activated carbon (AC) and calcium montmorillonite (CM) clay to decrease AMPA bioavailability from soil and AMPA translocation to plants. Adsorption isotherms and thermodynamic studies on AC and CM were conducted and showed tight binding (enthalpy values >-20 kJ/mol) for AMPA with high capacities (0.25 mol/kg and 0.38 mol/kg, respectively), based on derivations from the Langmuir model. A hydra assay was utilized to indicate toxicity of AMPA and the inclusion of 1% AC and CM both resulted in 90% protection of the hydra (**p ≤ 0.01). Further studies in glyphosate-contaminated soil showed that AC and CM significantly reduced AMPA bioavailability by 53% and 44%, respectively. Results in genetically modified (GM) corn showed a conversion of glyphosate to AMPA in roots and sprouts over a 10-day exposure duration. Inclusion of AC and CM reduced AMPA residues in roots and sprouts by 47%-61%. These studies collectively indicate that AC and CM are effective sorbents for AMPA and could be used to reduce AMPA bioavailability from soil and AMPA residues in GM corn plants.
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http://dx.doi.org/10.1016/j.jes.2020.06.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719843PMC
February 2021

Increase in aflatoxin exposure in two populations residing in East and West Texas, United States.

Int J Hyg Environ Health 2021 01 13;231:113662. Epub 2020 Nov 13.

Department of Environmental Health Science, The University of Georgia, Athens, GA, USA. Electronic address:

Although aflatoxin (AF) exposure has not been recognized as a major problem in the United States and other developed nations, recent global climate change may have a profound impact on distribution of toxigenic fungi growth and production of AFs in grain and groundnuts. Alterations in the contamination pattern can increase human dietary exposure, and further invoke public health concerns and associated disease risks. In this study, two populations from East and West Texas, known for their high risk of liver cancer, were examined for their AF exposure at three different time periods from 2004 to 2014. Serum samples (n = 1124) were collected from participants recruited for various studies from Bexar County and Lubbock County, TX, over the span of 2004 through 2014. The exposure biomarker, serum AFB-lysine adduct, was analyzed by HPLC-FLD and confirmed by LC-MS. Both populations showed a significant increase in detection rate, as well as median levels of serum AFB-lysine adduct over time, from 2.35 to 4.34 pg/mg albumin in East Texas (2007-2014), and 0.63-3.98 pg/mg albumin in West Texas (2004-2010). This observed shift in exposure likely represents a shift in the AF contamination pattern in the State of Texas, and may warrant further studies on risk assessment for the potential etiological effects of such increased exposures.
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http://dx.doi.org/10.1016/j.ijheh.2020.113662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771519PMC
January 2021

Testing the efficacy of broad-acting sorbents for environmental mixtures using isothermal analysis, mammalian cells, and H. vulgaris.

J Hazard Mater 2021 04 28;408:124425. Epub 2020 Oct 28.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. Electronic address:

The hazards associated with frequent exposure to polycyclic aromatic hydrocarbons (PAHs), pesticides, Aroclors, plasticizers, and mycotoxins are well established. Adsorption strategies have been proposed for the remediation of soil and water, although few have focused on the mitigation of mixtures. This study tested a hypothesis that broad-acting sorbents can be developed for diverse chemical mixtures. Adsorption of common and hazardous chemicals was characterized using isothermal analysis from Langmuir and Freundlich equations. The most effective sorbents included medical-grade activated carbon (AC), parent montmorillonite clay, acid-processed montmorillonite (APM), and nutrient-amended montmorillonite clays. Next, we tested the ability of broad-acting sorbents to prevent cytotoxicity of class-specific mixtures using 3 mammalian in vitro models (HLF, ESD3, and 3T3 cell lines) and the hydra assay. AC showed the highest efficacy for mitigating pesticides, plasticizers, PAHs, and mycotoxins. Clays, such as APM, were effective against pesticides, Aroclors, and mycotoxins, while amended clays were most effective against plasticizers. Finally, a sorbent mixture was shown to be broadly active. These results are supported by the high correlation coefficients for the Langmuir model with high capacity, affinity, and free energy, as well as the significant protection of cells and hydra (p < 0.05). The protection percentages in 3T3 cells and hydra showed the highest correlation as suggested by both Pearson and Spearman with r = 0.84 and rho = 0.73, respectively (p < 0.0001). Collectively, these studies showed that broad-acting sorbents may be effective in preventing toxic effects of chemical mixtures and provided information on the most effective sorbents based on adsorption isotherms, and in vitro and aquatic organism test methods.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904642PMC
April 2021

Enhanced adsorption of per- and polyfluoroalkyl substances (PFAS) by edible, nutrient-amended montmorillonite clays.

Water Res 2021 Jan 20;188:116534. Epub 2020 Oct 20.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. Electronic address:

Humans and animals are frequently exposed to PFAS (per- and polyfluoroalkyl substances) through drinking water and food; however, no therapeutic sorbent strategies have been developed to mitigate this problem. Montmorillonites amended with the common nutrients, carnitine and choline, were characterized for their ability to bind 4 representative PFAS (PFOA, PFOS, GenX, and PFBS). Adsorption/desorption isothermal analysis showed that PFOA, PFOS (and a mixture of the two) fit the Langmuir model with high binding capacity, affinity and enthalpy at conditions simulating the stomach. A low percentage of desorption occurred at conditions simulating the intestine. The results suggested that hydrophobic and electrostatic interactions, and hydrogen bonding were responsible for sequestering PFAS into clay interlayers. Molecular dynamics (MD) simulations suggested the key mode of interaction of PFAS was through fluorinated carbon chains, and confirmed that PFOA and PFOS had enhanced binding to amended clays compared to GenX and PFBS. The safety and efficacy of amended montmorillonite clays were confirmed in Hydra vulgaris, where a mixture of amended sorbents delivered the highest protection against a PFAS mixture. These important results suggest that the inclusion of edible, nutrient-amended clays with optimal affinity, capacity, and enthalpy can be used to decrease the bioavailability of PFAS from contaminated drinking water and diets.
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http://dx.doi.org/10.1016/j.watres.2020.116534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725962PMC
January 2021

Insights into the interactions of bisphenol and phthalate compounds with unamended and carnitine-amended montmorillonite clays.

Comput Chem Eng 2020 Dec 21;143. Epub 2020 Aug 21.

Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843, USA.

Montmorillonite clays could be promising sorbents to mitigate toxic compound exposures. Bisphenols A (BPA) and S (BPS) as well as phthalates, dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), are ubiquitous environmental contaminants linked to adverse health effects. Here, we combined computational and experimental methods to investigate the ability of montmorillonite clays to sorb these compounds. Molecular dynamics simulations predicted that parent, unamended, clay has higher binding propensity for BPA and BPS than for DBP and DEHP; carnitine-amended clay improved BPA and BPS binding, through carnitine simultaneously anchoring to the clay through its quaternary ammonium cation and forming hydrogen bonds with BPA and BPS. Experimental isothermal analysis confirmed that carnitine-amended clay has enhanced BPA binding capacity, affinity and enthalpy. Our studies demonstrate how computational and experimental methods, combined, can characterize clay binding and sorption of toxic compounds, paving the way for future investigation of clays to reduce BPA and BPS exposure.
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http://dx.doi.org/10.1016/j.compchemeng.2020.107063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591107PMC
December 2020

Tight sorption of arsenic, cadmium, mercury, and lead by edible activated carbon and acid-processed montmorillonite clay.

Environ Sci Pollut Res Int 2021 Feb 2;28(6):6758-6770. Epub 2020 Oct 2.

Veterinary Integrative Biosciences Department, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA.

Heavy metal exposure in humans and animals commonly occurs through the consumption of metal-contaminated drinking water and food. Although many studies have focused on the remediation of metals by purification of water using sorbents, limited therapeutic sorbent strategies have been developed to minimize human and animal exposures to contaminated water and food. To address this need, a medical grade activated carbon (MAC) and an acid processed montmorillonite clay (APM) were characterized for their ability to bind heavy metals and mixtures. Results of screening and adsorption/desorption isotherms showed that binding plots for arsenic, cadmium, and mercury sorption on surfaces of MAC (and lead on APM) fit the Langmuir model. The highest binding percentage, capacity, and affinity were shown in a simulated stomach model, and the lowest percentage desorption (< 18%) was shown in a simulated intestine model. The safety and protective ability of MAC and APM were confirmed in a living organism (Hydra vulgaris) where 0.1% MAC significantly protected the hydra against As, Cd, Hg, and a mixture of metals by 30-70%. In other studies, APM showed significant reduction (75%) of Pd toxicity, compared with MAC and heat-collapsed APM, suggesting that the interlayer of APM was important for Pb sorption. This is the first report showing that edible sorbents can bind mixtures of heavy metals in a simulated gastrointestinal tract and prevent their toxicity in a living organism. Graphical abstract.
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http://dx.doi.org/10.1007/s11356-020-10973-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855320PMC
February 2021

Potential Applications of Clay-Based Therapy for the Reduction of Pesticide Exposures in Humans and Animals.

Appl Sci (Basel) 2019 Dec 6;9(24). Epub 2019 Dec 6.

Veterinary Integrative Biosciences Department, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.

The risk of pesticide exposure in humans and animals may be magnified following natural and man-made disasters such as hurricanes and floods that can result in mobilization and redistribution of contaminated sediments. To develop broad-acting sorbents for mixtures of diverse toxins, we have processed calcium and sodium montmorillonite clays with high concentrations of sulfuric acid. These acid-processed montmorillonite clays (APMs) have shown limited hydration and swelling in water, higher surface areas, and lower trace metal levels than the parent clays, prior to processing. Isothermal analyses have indicated that newly developed APMs are highly active sorbents, with significantly increased binding capacities for a wide range of pesticides, including pentachlorophenol (PCP), 2,4,6-trichlorophenol (2,4,6-TCP), lindane, diazinon, linuron, trifluralin and paraquat. The safety and protective effects of APMs, against pesticide design mixtures, were confirmed in a living organism (). Further work is planned to confirm the safety of the APMs in long-term rodent studies. This is the first report of a sorbent material (other than carbon) with high binding efficacy for mixtures of these pesticides. Based on our results, APMs (and similar clays), may be able to decrease human and animal pesticide exposures during disasters and emergencies.
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http://dx.doi.org/10.3390/app9245325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494192PMC
December 2019

A high capacity bentonite clay for the sorption of aflatoxins.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2020 Feb 2;37(2):332-341. Epub 2019 Dec 2.

Department of Veterinary Integrative Biosciences, Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.

Previously a calcium bentonite clay (CB) has been shown to tightly bind aflatoxins , significantly reduce mortality and morbidity in animals, and decrease molecular biomarkers of aflatoxin exposure in humans and animals. Extensive studies have shown that CB is safe for human and animal consumption. In further work, we have investigated a highly active sodium bentonite (SB) clay (SB-E) with enhanced aflatoxin sorption efficacy compared to CB and other clays. Computational models and isothermal analyses were used to characterise toxin/clay surface interactions, predict mechanisms of toxin sorption, and gain insight into: 1) surface capacities and affinities, and 2) thermodynamics and sites of toxin/surface interactions. We have also used a toxin-sensitive living organism () to confirm the safety and predict the efficacy of SB-E against aflatoxin toxicity. Compared to CB, SB-E had a higher capacity for aflatoxin B (AfB) at pH 2 and 6.5. Results from this work suggest that high capacity clays such as SB-E can be used as effective aflatoxin enterosorbents to decrease short-term exposures in humans and animals when included in food and/or water during extended droughts and outbreaks of aflatoxicosis.
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http://dx.doi.org/10.1080/19440049.2019.1662493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989347PMC
February 2020

Strong Adsorption of Dieldrin by Parent and Processed Montmorillonite Clays.

Environ Toxicol Chem 2020 03 22;39(3):517-525. Epub 2020 Jan 22.

Veterinary Integrative Biosciences Department, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.

Widespread use of pesticides has resulted in the accumulation of pesticide residues in the environment due to their persistence and stability. To reduce potential exposures, we have developed broad-acting clay-based sorbents that can be included in the diet as enterosorbents to reduce the bioavailability and toxicity of chemicals. In the present study, parent and acid-processed calcium montmorillonite clays (CM and APM, respectively) were used to determine their potential as sorbents of the organochlorine insecticide dieldrin. We used adsorption isotherms, thermodynamics, and dosimetry studies to determine the capacities and affinities of the clays, the enthalpies of the binding reactions, and potential doses of sorbent that could protect against high exposures. Adsorption isotherms for APM fit a Langmuir model with high enthalpy (suggesting chemisorption) and high capacity (Q value = 0.45 mol kg ), indicating tight binding of dieldrin. Cultures of Hydra vulgaris were used to determine the ability of sorbents to protect a living organism from dieldrin toxicity. The inclusion of acid-processed clays resulted in the highest reduction of dieldrin toxicity (70%) in the hydra. Further work indicated that both CM and APM can significantly reduce the bioavailability of dieldrin from soil (p ≤ 0.01). These results suggest that APM (and similar clays) can be effective sorbents of dieldrin and may be included in the diet and/or soil to protect against environmental exposures. Environ Toxicol Chem 2020;39:517-525. © 2019 SETAC.
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http://dx.doi.org/10.1002/etc.4642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047628PMC
March 2020

Tall Fescue and Genetics Influence Root-Associated Soil Fungi in a Temperate Grassland.

Front Microbiol 2019 15;10:2380. Epub 2019 Oct 15.

Department of Plant and Soil Sciences, University of Kentucky, Lexington, KY, United States.

A constitutive, host-specific symbiosis exists between the aboveground fungal endophyte (Morgan-Jones & W. Gams) and the cool-season grass tall fescue ( (Schreb.) Darbysh.), which is a common forage grass in the United States, Australia, New Zealand, and temperate European grasslands. New cultivars of tall fescue are continually developed to improve pasture productivity and animal health by manipulating both grass and genetics, yet how these selected grass-endophyte combinations impact other microbial symbionts such as mycorrhizal and dark septate fungi remains unclear. Without better characterizing how genetically distinct grass-endophyte combinations interact with belowground microorganisms, we cannot determine how adoption of new -symbiotic cultivars in pasture systems will influence long-term soil characteristics and ecosystem function. Here, we examined how presence and host × endophyte genetic combinations control root colonization by belowground symbiotic fungi and associated plant nutrient concentrations and soil properties in a 2-year manipulative field experiment. We used four vegetative clone pairs of tall fescue that consisted of one endophyte-free (E-) and one -symbiotic (E+) clone each, where E+ clones within each pair contained one of four endophyte genotypes: CTE14, CTE45, NTE16, or NTE19. After 2 years of growth in field plots, we measured root colonization of arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE), extraradical AMF hyphae in soil, total C, N, and P in root and shoot samples, as well as C and N in associated soils. Although we observed no effects of presence or symbiotic genotype on total AMF or DSE colonization rates in roots, different grass-endophyte combinations altered AMF arbuscule presence and extraradical hyphal length in soil. The CTE45 genotype hosted the fewest AMF arbuscules regardless of endophyte presence, and E+ clones within NTE19 supported significantly greater soil extraradical hyphae compared to E- clones. Because AMF are often associated with improved soil physical characteristics and C sequestration, our results suggest that development and use of unique grass-endophyte combinations may cause divergent effects on long-term ecosystem properties.
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http://dx.doi.org/10.3389/fmicb.2019.02380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843077PMC
October 2019

Montmorillonites Can Tightly Bind Glyphosate and Paraquat Reducing Toxin Exposures and Toxicity.

ACS Omega 2019 Oct 17;4(18):17702-17713. Epub 2019 Oct 17.

Veterinary Integrative Biosciences Department, College of Veterinary Medicine and Biomedical Sciences and Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, United States.

Among the numerous contaminants of soil, glyphosate and paraquat are two of the most widely used herbicides that are commonly detected in the environment. Soil and sediment contaminated with glyphosate, paraquat, and other environmental toxins can be mobilized and redistributed to lawns, vegetable gardens, parks, and water supplies in vulnerable communities at the site of disasters such as hurricanes and flooding. Glyphosate and paraquat bind strongly to soils containing clays, making their bioavailability (bioaccessibility) from these types of soil very low. Because of their affinity for clay-based soils, it is possible that montmorillonite clays could be administered as a therapeutic agent in the diet of animals and humans to decrease short-term exposure and toxicity. In this study, we investigated the sorption mechanisms of glyphosate and paraquat onto active surfaces of calcium montmorillonite (CM) and sodium montmorillonite (SM) clays and derived binding parameters, including capacity, affinity, and enthalpy. Additionally, we used these parameters to predict the reduction in bioavailability under different pH and temperature conditions and to estimate the theoretical dose of clay that could protect against severe paraquat toxicity and lethality. Computational modeling and simulation studies depicted toxin sorption mechanisms at different pH values. Additionally, a toxin-sensitive living organism () was used to confirm the safety of the clay and its ability to protect against toxicity from glyphosate and paraquat. The high efficacy of CM and SM shown in this study supports the natural binding activity of glyphosate and paraquat to clay-based soils. Following disasters and medical emergencies, montmorillonite clays could be administered by capsules and tablets, or added to food and flavored water, to reduce toxin bioavailability and human and animal exposures.
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http://dx.doi.org/10.1021/acsomega.9b02051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822125PMC
October 2019

Strong adsorption of Polychlorinated Biphenyls by processed montmorillonite clays: Potential applications as toxin enterosorbents during disasters and floods.

Environ Pollut 2019 Dec 7;255(Pt 1):113210. Epub 2019 Sep 7.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA. Electronic address:

Polychlorinated biphenyls (PCBs) have been detected as prevalent environmental contaminants in water, food and biota. Previous studies in vitro have shown that a variety of sorbent materials, including carbon, can sorb PCBs; however, PCB sorbents that can be added to food or drinking water to decrease toxin bioavailability in humans and animals have not been reported. To address this problem, we have developed broad-acting and highly effective sorbents for PCBs using montmorillonite clays reported to be safe for consumption in animals and humans. In this study, calcium montmorillonite clays were acid processed (APMs) and the interactions of six PCB congeners (PCB 77, 126, 153, 157, 154 and 155) on the surfaces of APMs were characterized. Computational models and isothermal analyses were used to derive surface capacities and affinities, delineate mechanisms and predict the thermodynamics of sorption. To confirm the safety and predict the efficacy of APMs against individual PCBs and common mixtures (Aroclors 1254 and 1260), we have also used a living organism (Hydra vulgaris) that is sensitive to toxins. APMs significantly protected hydra against the toxicity of PCBs and Aroclors. This finding was supported by studies showing tight binding; high capacity, affinity, and enthalpy; and a low therapeutic dose.
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http://dx.doi.org/10.1016/j.envpol.2019.113210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878994PMC
December 2019

Development of broad-acting clays for the tight adsorption of benzo[a]pyrene and aldicarb.

Appl Clay Sci 2019 Feb 20;168:196-202. Epub 2018 Nov 20.

Veterinary Integrative Biosciences Department, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.

People and animals can be unintentionally exposed to complex mixtures of hazardous chemicals that can threaten the safety of food and water supplies following natural and man-made disasters and emergencies. Our research has focused on the development of broad-acting adsorbents that will tightly bind environmental contaminants in the gastrointestinal tract and decrease their bioavailability to humans and animals during these events. In this study, benzo[a]pyrene (BaP) and aldicarb were used as representative chemicals due to their high toxicity and extensive distribution in the environment. Both chemicals have been commonly detected in water and sediments in the US, and their distribution and concentrations can be enhanced during disasters. To address this problem, we have amended and functionalized montmorillonite clays with the nutrients, L-carnitine and choline to enhance their attraction for lipophilic toxins, such as BaP and aldicarb. Based on equilibrium isothermal analyses, we have demonstrated a significantly increased binding capacity (Qmax) and affinity (Kd) for BaP and aldicarb compared to the parent clay. Adsorption isotherms also showed that talc bound strongly to BaP with the highest Qmax, which was twice that of activated carbon. Additionally, cultures of adult hydra with a metabolism activation package were used as an toxicity indicator to confirm the ability of test adsorbents to protect against toxicity at low inclusion levels. We anticipate that the optimal adsorbents developed can be delivered in food and flavored water, or administered by sachet or capsule during emergencies and disasters to decrease human and animals exposures to environmental toxins.
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http://dx.doi.org/10.1016/j.clay.2018.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703832PMC
February 2019

Development of enterosorbents that can be added to food and water to reduce toxin exposures during disasters.

J Environ Sci Health B 2019 24;54(6):514-524. Epub 2019 Apr 24.

a Veterinary Integrative Biosciences Department, College of Veterinary Medicine and Biomedical Sciences , Texas A&M University , College Station , Texas , USA.

Humans and animals can be exposed to mixtures of chemicals from food and water, especially during disasters such as extended droughts, hurricanes and floods. Drought stress facilitates the occurrence of mycotoxins such as aflatoxins B (AfB) and zearalenone (ZEN), while hurricanes and floods can mobilize toxic soil and sediments containing important pesticides (such as glyphosate). To address this problem in food, feed and water, we developed broad-acting, clay-based enterosorbents that can reduce toxin exposures when included in the diet. In this study, we processed sodium and calcium montmorillonite clays with high concentrations of sulfuric acid to increase surface areas and porosities, and conducted equilibrium isothermal analyses and dosimetry studies to derive binding parameters and gain insight into: (1) surface capacities and affinities, (2) potential mechanisms of sorption, (3) thermodynamics (enthalpy) of toxin/surface interactions and (4) estimated dose of sorbent required to maintain toxin threshold limits. We have also used a toxin-sensitive living organism () to predict the safety and efficacy of newly developed sorbents. Our results indicated that acid processed montmorillonites were effective sorbents for AfB, ZEN and glyphosate, with high capacity and tight binding, and effectively protected hydra against individual toxins, as well as mixtures of mycotoxins.
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http://dx.doi.org/10.1080/03601234.2019.1604039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681816PMC
August 2019

NovaSil clay for the protection of humans and animals from aflatoxins and other contaminants.

Clays Clay Miner 2019 Feb 5;67(1):99-110. Epub 2019 Apr 5.

Interdisciplinary Toxicology Program and Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia 30602, USA.

Aflatoxin contamination of diets results in disease and death in humans and animals. The objective of the present paper was to review the development of innovative enterosorption strategies for the detoxification of aflatoxins. NovaSil clay (NS) has been shown to decrease exposures to aflatoxins and prevent aflatoxicosis in a variety of animals when included in their diets. Results have shown that NS clay binds aflatoxins with high affinity and high capacity in the gastrointestinal tract, resulting in a notable reduction in the bioavailability of these toxins without interfering with the utilization of vitamins and other micronutrients. This strategy is already being utilized as a potential remedy for acute aflatoxicosis in animals, and as a sustainable intervention diet. Animal and human studies have confirmed the apparent safety of NS and refined NS clay (with uniform particle size). Studies in Ghanaians at high risk of aflatoxicosis have indicated that NS (at a dose level of 0.25% w/w) is effective at decreasing biomarkers of aflatoxin exposure and does not interfere with levels of serum vitamins A and E, or iron or zinc. A new spinoff of this strategy is the development and use of broad-acting sorbents for the mitigation of environmental chemicals and microbes during natural disasters and emergencies. In summary, enterosorption strategies/therapies based on NS clay are promising for the management of aflatoxins and as sustainable public health interventions. The NS clay remedy is novel, inexpensive, and easily disseminated.
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http://dx.doi.org/10.1007/s42860-019-0008-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494129PMC
February 2019

Optimal Chemical Grouping and Sorbent Material Design by Data Analysis, Modeling and Dimensionality Reduction Techniques.

ESCAPE 2018 4;43:421-426. Epub 2018 Jul 4.

Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843, USA.

The ultimate goal of the Texas A&M Superfund program is to develop comprehensive tools and models for addressing exposure to chemical mixtures during environmental emergency-related contamination events. With that goal, we aim to design a framework for optimal grouping of chemical mixtures based on their chemical characteristics and bioactivity properties, and facilitate comparative assessment of their human health impacts through read-across. The optimal clustering of the chemical mixtures guides the selection of sorption material in such a way that the adverse health effects of each group are mitigated. Here, we perform (i) hierarchical clustering of complex substances using chemical and biological data, and (ii) predictive modeling of the sorption activity of broad-acting materials via regression techniques. Dimensionality reduction techniques are also incorporated to further improve the results. We adopt several recent examples of chemical substances of Unknown or Variable composition Complex reaction products and Biological materials (UVCB) as benchmark complex substances, where the grouping of them is optimized by maximizing the Fowlkes-Mallows (FM) index. The effect of clustering method and different visualization techniques are shown to influence the communication of the groupings for read-across.
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http://dx.doi.org/10.1016/B978-0-444-64235-6.50076-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284807PMC
July 2018

Modulation of pre-neoplastic biomarkers induced by sequential aflatoxin B and fumonisin B exposure in F344 rats treated with UPSN clay.

Food Chem Toxicol 2018 Apr 26;114:316-324. Epub 2018 Feb 26.

Department of Environmental Health Science, University of Georgia, Athens, GA, USA. Electronic address:

Populations consuming aflatoxin (AF) and fumonisin (FN)-contaminated foods may be at increased risk for hepatocellular carcinoma (HCC) and developmental disorders; consequently, development of intervention strategies to reduce AF/FN-induced liver disease and adverse health effects in humans could be very useful. Calcium montmorillonite clay (NovaSil) has been shown to absorb AF in vitro, in multiple animal models, as well as in human studies. In the present study, we aimed to evaluate whether uniform particle size NovaSil (UPSN) possessed an ability to modulate the co-carcinogenic potentials of aflatoxin B (AFB) and fumonisin B (FB) in F344 rats. Sequential treatment of FB following AFB synergistically induces preneoplastic alterations as well as liver damage, indicating that AFB acts as an initiator while FB as a promoter in the carcinogenesis model, confirming findings from previous studies. The enterosorbent agent UPSN clay at dose of up to 0.5% in diet was shown to be effective in modulating the toxicity and carcinogenicity of co-exposure to AFB and FB, as demonstrated by significant reduction in number and size of hepatic GST-P foci, in alterations indicative of liver toxicity, and in levels of AFB and FB biomarkers.
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http://dx.doi.org/10.1016/j.fct.2018.02.048DOI Listing
April 2018

Development of High Capacity Enterosorbents for Aflatoxin B1 and Other Hazardous Chemicals.

Chem Res Toxicol 2017 09 5;30(9):1694-1701. Epub 2017 Sep 5.

Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, Texas 77845, United States.

Previously, a calcium montmorillonite clay (NovaSil) included in the diet of animals has been shown to bind aflatoxin B1 (AfB1) and reduce the symptoms of aflatoxicosis. To investigate and improve the capacity and efficacy of clay-based materials as aflatoxin sorbents, we developed and tested calcium and sodium montmorillonite clays amended with nutrients including l-carnitine and choline. Also, we determined the sorption of AfB1 by isothermal analysis and tested the ability of these amended sorbents to protect adult hydra from AfB1 toxicity. The results showed that exchanging montmorillonite clays with l-carnitine and choline inhibited swelling of the clays and increased the sorption capacity and efficacy of clay surfaces for AfB1. Results from dehydroxylated and heat-collapsed clays suggested that AfB1 was primarily adsorbed in the clay interlayer, as predicted from thermodynamic calculations and computational modeling. The hydra bioassay further indicated that the modified clays can significantly protect adult hydra from AfB1 with as low as 0.005% clay inclusion. This enterosorbent therapy may also be applied to screen hazardous chemicals such as pesticides and PAHs based on similar sorption mechanisms. Taken together, enterosorbent therapy could be delivered in nutritional supplements, foods that are vulnerable to aflatoxin contamination, flavored liquids and animal feeds during emergencies and outbreaks of acute aflatoxicosis, and as a screening model for hazardous environmental chemicals.
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http://dx.doi.org/10.1021/acs.chemrestox.7b00154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684212PMC
September 2017

Early Access to Physical Therapy and Specialty Care Management for American Workers With Musculoskeletal Injuries.

J Occup Environ Med 2017 04;59(4):402-411

Spectrum Health Rehabilitation Services, Grand Rapids, Michigan (Dr Phillips); and Spectrum Health Rehabilitation Services, Grand Rapids, Michigan (Dr Shoemaker).

Objective: The aim of this study was to investigate the effect of very early access to physical therapy and specialty care management in a workers' compensation population.

Methods: A prospective pilot (n = 75) was conducted from 2012 to 2013 in which injured workers with musculoskeletal complaints received physical therapy and started care management during their initial occupational medicine clinic visit. Two retrospective comparator groups with workers' compensation claims from 2009 and 2012 were included in this study.

Results: When comparing 2009 data with the 2012 to 2013 prospective pilot study, statistically significant differences were noted in favor of the prospective pilot for total costs per claim, cost of indemnity, number of therapy visits, and time to access physical therapy. When compared with the 2012 nonpilot cohort, differences were not statistically significant.

Conclusions: Expedited access to physical therapy and care management can reduce duration of care, cost of claims, and therapy visits.
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http://dx.doi.org/10.1097/JOM.0000000000000969DOI Listing
April 2017

Pregnane X receptor regulates the AhR/Cyp1A1 pathway and protects liver cells from benzo-[α]-pyrene-induced DNA damage.

Toxicol Lett 2017 Jun 18;275:67-76. Epub 2017 Apr 18.

College of Veterinary Medicine, Hunan Agriculture University, Hunan, China; Department of Veterinary Physiology and Pharmacology, Texas A&M University, USA. Electronic address:

Pregnane X receptor (PXR) plays an important role in protecting cells from mutagenic DNA damages induced by endogenous and exogenous toxicants. This protective function is often attributed to the PXR-regulated metabolic detoxification. Here we report a novel potential mechanism that PXR reduces benzo-[α]-pyrene(BaP)-induced DNA damage through inhibiting the transcriptional activity of aryl hydrocarbon receptor (AhR) which plays a pivotal role in the bioactivation of BaP. We have utilized three well-characterized cell lines, i.e. Hepa1c1c7, AhR +/+; Bpr lacks AhR obligatory partner ARNT; Tao, lacks AhR, to analyze pivotal role of AhR/ARNT complex in mediating the BaP-induced DNA damages using comet assay (single-cell gel electrophoresis). We found that PXR activation could significantly inhibit BaP-induced DNA damage in the HepG2 cells as well as mouse hepatocytes. Using PXR-null and wild type mouse hepatocytes we showed that PXR activation by pregnenolone 16α-carbonitrile (PCN) significantly inhibited BaP-induced DNA damage and this protective effect was abolished in PXR-null hepatocytes. Mechanistically, PXR activation inhibited expression of AhR-target genes for CYP1A1, CYP1B1 and CYP1A2 that are required for BaP biotransformation in cultured liver cells, or in the livers of C57BL/6J mice. Using an AhR-responsive reporter assay as well as chromatin immunoprecipitation assay we found that PXR activation transcriptionally represses AhR-regulated gene expression. Furthermore, we found that PXR directly bound AhR at its DNA-binding domain, and this association may play a role in preventing of the AhR from binding to its target genes as shown in the ChIP assay. Taken together, our study has revealed a novel mechanism by which PXR protects liver cells from BaP-induced DNA damage through inhibiting the BaP biotransformation.
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http://dx.doi.org/10.1016/j.toxlet.2017.03.028DOI Listing
June 2017

Lifestyle and Clinical Correlates of Hepatocellular Carcinoma in South Texas: A Matched Case-control Study.

Clin Gastroenterol Hepatol 2017 08 23;15(8):1311-1312. Epub 2017 Mar 23.

Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, California.

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http://dx.doi.org/10.1016/j.cgh.2017.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071406PMC
August 2017
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