Absorption Of Chemicals Research Articles

Elucidating impacts of partitioning and transmembrane permeability on absorption of chemicals in human gastrointestinal tract

Estimating the fraction absorbed (Fabs) of orally ingested chemicals in the human gastrointestinal tract is pivotal for assessing chemical concentrations in the systemic circulation and informing potential toxicological impacts, especially in the era of “new approach methods” targeting chemical screening and prioritization. Here, we present an input-parsimonious and computationally efficient approach to support the screening-level estimation of Fabs from partitioning (characterized using the octanol–water partition coefficient at pH 7.4, KOW) and transmembrane permeability (characterized using the Caco-2 apparent permeability, Papp,Caco-2), based on a mechanistic description of processes involved in chemical absorption:Fabs=1-e-164571-2.40×10-9+2.40×10-9∙KOW∙10.0075∙1Papp,Caco-2-10.001530.346+10.00115Our approach demonstrates satisfactory performance in predicting Fabs for 176 hydrophobic and hydrophilic organic chemicals, with a Pearson correlation coefficient greater than 0.75 and a root mean square error of approximately 15 % in absolute Fabs values between experimental measurements and predictions. Our results show that the Fabs of highly hydrophobic chemicals (KOW > 108) are closely dependent on partitioning, whereas the Fabs of relatively hydrophilic chemicals (KOW < 106) are sensitive to transmembrane permeability. We also demonstrate that transmembrane permeability and partitioning are not interdependent, and both should be treated as fundamental chemical properties in predicting Fabs.

Observations on the Tritiated Water and TEWL Skin Integrity Tests: Relevance to In Vitro Permeation Testing (IVPT).

The in vitro permeation test (IVPT) using ex vivo human skin is a sensitive and robust model system that has been vital in elucidating the fundamental parameters surrounding the absorption of both therapeutic agents and industrial chemicals through skin. FDA and OECD IVPT Guidances recommend that each skin section selected for study should be screened prior to use to ensure that the stratum corneum integrity is retained. Three methods are currently considered acceptable: 1) transepidermal water loss (TEWL), 2) electrical resistance, and 3) tritiated water (3H2O) absorption. A retrospective analysis of data from the authors' laboratory has been performed with the objective of addressing a number of questions regarding the 3H2O and TEWL integrity tests, and the population attributes of a large database consisting of 17,330 individual skin sections obtained from 459 skin donors. The applicability and usefulness of these tests, when compared to companion permeation data obtained from 25 topical drug products, has also been examined. Both integrity tests found water permeability to be equal in White and Hispanic races but higher than in Blacks, 3H2O being more discriminating than TEWL. Male skin is more permeable than female and there is a slight decrease in permeability with advancing age in both groups. Correlation between 3H2O absorption and drug absorption revealed a minimal relationship between the two in most cases, the Pearson correlation coefficient ranging from -0.417 to 0.953. Additionally, drug outliers were not always identified with a failing integrity test. The results call for a critical reexamination of the value of the 3H2O integrity test, and by extension, TEWL, for use in IVPT studies.

QM, Fukui function, molecular docking, molecular dynamics investigation on Human Estrogen Receptor (HER) with Clioquinol

Clioquinol is an antifungal medication that is used to treat skin diseases such as dermatitis, foot inflammation, sports itch, and ringworm The electron localization and delocalization indices in position space are further quantum chemical instruments that are commonly utilized to understand complex chemical bonding conditions in molecules and solids. LOL is carried out and it's the three-dimensional function of kinetic energy density, and its interpretation is based on the fact that is small in the bonding region. Fukui functions are chemical descriptors that can be used to explain how systems react to electron movement. Molecular docking determines the ligand binding affinity with protein receptors by utilizing the atomic-level coordination processes of molecular interactions that occur between them. A docking study was carried out for Human Estrogen Receptors with the ligand Cloquinol. Through the properties of the molecules, the ligand behavior is analyzed by using Molecular Dynamics. Absorption, Distribution, Metabolism, Excretion, and Toxicity of chemicals a crucial components in the discovery and development of novel medications. A good drug candidate should exhibit the right therapeutic dose, ADMET properties, and adequate efficacy against the therapeutic target.

A facile strategy for improving the hydrophobicity and photo-thermal conversion capability of biochar and its application in the absorption of hazardous chemicals and viscous oil

Biochar is considered as a promising adsorbent due to its unique porous structure, large surface area and lightweight nature. In this study, pomelo peel was used as raw material, and graphene oxide was introduced as a functional material. High-temperature carbonization was employed to achieve simultaneous carbonization of pomelo peel and thermal reduction of graphene oxide, resulting in the preparation of a porous sponge-like biochar with high hydrophobicity, thermal stability and photothermal conversion capability. This biochar was successfully applied to the efficient separation of various oil–water mixtures, demonstrating excellent cyclic adsorption stability. Furthermore, by harnessing its photothermal conversion effect, efficient absorption of viscous oil product was achieved. This study proposes a facile biochar preparation strategy that can expand its application in the field of oil spill emergency treatment and promote the utilization of agricultural waste.

Multitask learning for predicting pulmonary absorption of chemicals

Pulmonary absorption is an important route for drug delivery and chemical exposure. To streamline the chemical assessment process for the reduction of animal experiments, several animal-free models were developed for pulmonary absorption research. While Calu-3 and Caco-2 cells and their derived computational models were used in estimating pulmonary permeability, the ex vivo isolated perfused lung (IPL) models are considered more clinically relevant measurements. However, the IPL experiments are resource-consuming making it infeasible for the large-scale screening of potential inhaled toxicants and drugs. In silico models are desirable for estimating pulmonary absorption. This study presented a novel machine learning method that employed an extratrees-based multitask learning approach to predict the IPL absorption rate constant (kaIPL) of various chemicals. The shared permeability knowledge was extracted by simultaneously learning three relevant tasks of Caco-2 and Calu-3 cell permeability and IPL absorption rate. Seven informative physicochemical descriptors were identified. A rigorous evaluation of the developed prediction model showed good performance with a high correlation between predictions and observations (r = 0.84) in the independent test dataset. Two case studies of inhalation drugs and respiratory sensitizers revealed the potential application of this model, which may serve as a valuable tool for predicting pulmonary absorption of chemicals.

Critical Review of Lipstick Toxicity with Reference to Dushivisha

Sthavara poison of plant origin Jangama poison of animal origin and Garavisha artificial poisoning are the three categories of poison according to Ayurveda. There is no distinct classification for the Dushivisha but according to Ayurveda it is either Sthavara Jangama or Krtrima visha. When following therapy it loses some of its potency but does not completely lose its effects. For this reason it is classified in this category. When a human is exposed for an extended length of time repeatedly cumulative poison which is weaker and less potent in its action accumulates within the tissues of the person. The most popular cosmetic item lipstick is made up of several different chemicals. The majority of lipsticks are mixtures of chemicals including petroleum paraffins phthalates lead and other hazardous metals coal tar colors and fragrance. Long-term lipstick usage results in direct ingestion or absorption of harmful chemicals into the body through mucosal membrane or oral cavity. After prolonged use these accumulated chemicals start to exert detrimental effects on the body. Thus continuous exposure can result in harmful effects on the brain system as well as endocrine problems allergies and skin irritants. Ayurveda refers to this kind of poisoning as a Dushivisha.

Bridging toxicological properties of environmental chemicals between animals and humans using healthy organoid systems.

The application of organoids derived from animal tissues and human-induced pluripotent stem cells to safety assessments of environmental chemicals has been introduced over the last decade. One of the objectives of this approach is to develop an alternative method for animal toxicological studies, while another is to focus on the local reactions of chemicals in each organ/tissue. One of the most important goals is bridging the toxicological properties of chemicals between animals and humans, which may be compared on a level playing field using healthy organoids derived from both animals and humans in vitro, excluding species difference in the absorption, distribution, metabolism, and excretion properties of chemicals in vivo. An overview of the application of organoid systems to safety assessments of environmental chemicals, including general toxicology, developmental toxicology, carcinogenicity, and mutagenicity, was provided herein, and bridging strategies using both animal and human organoids are proposed as a future perspective.

Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions.

Quantitative structure permeation relationship (QSPR) models have gained prominence in recent years owing to their capacity to elucidate the influence of physicochemical properties on the dermal absorption of chemicals. These models facilitate the prediction of permeation coefficient (Kp) values, indicating the skin permeability of a chemical under infinite dose conditions. Conversely, obtaining dermal absorption rates (DAs) under finite dose conditions, which are crucial for skin product safety evaluation, remains a challenge when relying solely on Kp predictions from QSPR models. One proposed resolution involves using Kroes' methodology, categorizing DAs based on Kp values; however, refinement becomes necessary owing to discreteness in the obtained values. We previously developed a mathematical model using Kp values obtained from in vitro dermal absorption tests to predict DAs. The present study introduces a new methodology, Integrating Mathematical Approaches (IMAS), which combines QSPR models and our mathematical model to predict DAs for risk assessments without conducting in vitro dermal absorption tests. Regarding 40 chemicals (76.1 ≤ MW ≤ 220; -1.4 ≤ Log Ko/w ≤ 3.1), IMAS showed that 65.0% (26/40) predictions of DA values were accurate to within twofold of the observed values in finite dose experiments. Compared to Kroes' methodology, IMAS notably mitigated overestimation, particularly for hydrophilic chemicals with water solubility exceeding 57.0 mg/cm3. These findings highlight the value of IMAS as a tool for skin product risk assessments, particularly for hydrophilic compounds.

Hydrogen‐Bonded Organic Frameworks Based on Endless‐Stacked Amides for Iodine Capture and Detection

AbstractRecently, hydrogen‐bonded organic frameworks (HOFs) have emerged as a rapidly advancing class of porous materials with significant potential for applications in the absorption and detection of various chemicals. Here, the unique ability of amide groups to form endless‐stacking H‐bonds is implemented in the design of HOFs. Starting from benzene‐1,3,5‐tricarboxamide and amide‐containing tribenzocyclynes as foundational building blocks, a diverse range of HOFs featuring 1D, 2D, or 3D hydrogen‐bonded frameworks has been synthesized. Among those, all three porous HOFs, HOF_B‐Hex, HOF_T‐Pr and HOF_T‐Hex exhibited permanent porosity, thereby demonstrating the effectiveness of amide‐based HOFs strategy. Notably, HOF_T‐Hex stands out with a 42% pore volume and an impressive iodine capture efficiency of 6.4 g g−1. The iodine capture capacity is influenced not only by pore volume but also by the presence of accessible π‐electrons within the material (i.e., electrons not engaged in a π–π stacking interaction. Furthermore, some of these HOFs exhibited fluorescent responses to iodine positioning them as highly promising materials for both the capture and sensing of iodine.

A compartment model to predict in vitro finite dose absorption of chemicals by human skin

Dermal uptake is an important and complex exposure route for a wide range of chemicals. Dermal exposure can occur due to occupational settings, pharmaceutical applications, environmental contamination, or consumer product use. The large range of both chemicals and scenarios of interest makes it difficult to perform generalizable experiments, creating a need for a generic model to simulate various scenarios. In this study, a model consisting of a series of four well-mixed compartments, representing the source solution (vehicle), stratum corneum, viable tissue, and receptor fluid, was developed for predicting dermal absorption. The model considers experimental conditions including small applied doses as well as evaporation of the vehicle and chemical. To evaluate the model assumptions, we compare model predictions for a set of 26 chemicals to finite dose in-vitro experiments from a single laboratory using steady-state permeability coefficient and equilibrium partition coefficient data derived from in-vitro experiments of infinite dose exposures to these same chemicals from a different laboratory. We find that the model accurately predicts, to within an order of magnitude, total absorption after 24 h for 19 of these chemicals. In combination with key information on experimental conditions, the model is generalizable and can advance efficient assessment of dermal exposure for chemical risk assessment.

The Application of a Physiologically Based Toxicokinetic Model in Health Risk Assessment.

Toxicokinetics plays a crucial role in the health risk assessments of xenobiotics. Classical compartmental models are limited in their ability to determine chemical concentrations in specific organs or tissues, particularly target organs or tissues, and their limited interspecific and exposure route extrapolation hinders satisfactory health risk assessment. In contrast, physiologically based toxicokinetic (PBTK) models quantitatively describe the absorption, distribution, metabolism, and excretion of chemicals across various exposure routes and doses in organisms, establishing correlations with toxic effects. Consequently, PBTK models serve as potent tools for extrapolation and provide a theoretical foundation for health risk assessment and management. This review outlines the construction and application of PBTK models in health risk assessment while analyzing their limitations and future perspectives.

Explore the Dosimetric Relationship between the Intake of Chemical Contaminants and Their Occurrence in Blood and Urine.

The dosimetric relationship between the human intake dose of a chemical contaminant (an "external dose") and its concentrations in bodily fluids such as blood and urine (related to an "internal dose"), often characterized by a dose-to-concentration ratio, has critical applications in exposure science, toxicology, and risk assessment, especially in the "new approach methods" era. However, there is a lack of a mechanistic, systematic understanding of how such a dosimetric relationship depends on fundamental chemical properties, such as partition coefficients and biotransformation half-lives. Here, we investigate this issue using a well-evaluated toxicokinetic model, which links external and internal doses by quantifying the absorption and elimination of chemicals. Results are visualized in a series of chemical partitioning space plots, whereby a chemical's dose-to-concentration ratio can be approximately predicted based on its partitioning between air, water, and octanol phases. Our results indicate that when taken in equal doses, chemicals with low volatility and moderate to high hydrophobicity exhibit the highest concentrations in the blood, and chemicals undergoing significant biotransformation tend to exhibit lower concentrations in comparison to their counterparts undergoing negligible biotransformation but possessing similar partitioning properties. Chemicals with high hydrophilicity have the highest concentrations in urine. Such revealed property dependence is similar for both adults and children and for individuals with normal body weights and with obesity. Overall, insights gained from this study are important in predicting blood and urinary concentrations from exposure information and in determining the exposure rate that produces the blood or urinary concentrations observed in biomonitoring studies.

Review Article: Skin Condition and Skin Care in Premature Infants

Background: The majority of newborn skin care recommendations focus on concerns for healthy, full-term infants. Compared to mature infants, the skin of premature infants, those who are born at the gestational age of 37 weeks, is more vulnerable to injury, transepidermal water loss (TEWL), and transepidermal intoxication. There are no established guidelines for premature infant skin care. Discussion and review regarding this topic are needed. Purpose: To review the literature on skin conditions and skin care in premature infants. Review: The barrier function of premature skin is significantly compromised because the stratum corneum does not fully mature until late in the third trimester. Premature infants have immature skin with impaired barrier function characterized by high TEWL, increased absorption of chemicals, and increased risk of infection. Some particular issues in premature infant skin are controlling TEWL, avoiding mechanical damage, proper sterilization to control infection, awareness of percutaneous drug toxicity, appropriate bathing and umbilical cord care, and appropriate management of skin problems. Conclusion: Premature infant skin is more vulnerable due to immature development. Skin care for premature infants requires careful attention.

Microplastics Scoping Review of Environmental and Human Exposure Data

Scientific studies of microplastics have expanded since 2015, propelling the topic to the forefront of scientific inquiry. Microplastics are ubiquitous in the environment and pose a potential risk to human health. The purpose of this review is to organize microplastics literature into areas of scientific research, summarize the state of the literature and identify the current data gaps in knowledge to promote a better understanding of human exposure to microplastics and their potential health effects. We searched for published literature from eight databases. Our search focused on three categories: (1) microplastics in the environment, (2) adsorption and absorption of chemicals to microplastics, and (3) human exposure to microplastics in the environment. We screened all abstracts to select articles that focused on microplastics. We then screened the remaining articles using criteria outlined in a questionnaire to identify and assign articles to the three scoping review categories. After screening abstracts, we selected 1186 articles (19%) to thoroughly assess their appropriateness for inclusion in the final review. Of the 1186 articles, 903 (76.1%) belonged to the environmental category, 268 (22.6%) to the adsorption and absorption category, and 16 (1.3%) to the human exposure category. Water was the most frequently studied environmental medium (440 articles). Our assessment resulted in 572 articles selected for the final review. Of the 572 publications, 268 (48.2%) included a geographic component and 110 (19.2%) were the product of literature reviews. We also show that relatively few publications have investigated human health effects associated with exposures to microplastics.

A regression analysis using simple descriptors for multiple dermal datasets: Going from individual membranes to the full skin.

In silico methods to estimate and/or quantify skin absorption of chemicals as a function of chemistry are needed to realistically predict pharmacological, occupational, and environmental exposures. The Potts-Guy equation is a well-established approach, using multi-linear regression analysis describing skin permeability (Kp) in terms of the octanol/water partition coefficient (logP) and molecular weight (MW). In this work, we obtained regression equations for different human datasets relevant to environmental and cosmetic chemicals. Since the Potts-Guy equation was published in 1992, we explored recent datasets that include different skin layers, such as dermatomed (including dermis to a defined thickness) and full skin. Our work was consistent with others who have observed that fits to the Potts-Guy equation are stronger for experiments focused on the epidermis. Permeability estimates for dermatomed skin and full skin resulted in low regression coefficients when compared to epidermis datasets. An updated regression equation uses a combination of fitted permeability values obtained with a published 2D compartmental model previously evaluated. The resulting regression equation was: logKp = -2.55 + 0.65logP - 0.0085MW, R2 = 0.91 (applicability domain for all datasets: MW ranges from 18 to >584 g/mol and -4 to >5 for logP). This approach demonstrates the advantage of combining mechanistic with structural activity relationships in a single modeling approach. This combination approach results in an improved regression fit when compared to permeability estimates obtained using the Potts-Guy approach alone. The analysis presented in this work assumes a one-compartment skin absorption route; future modeling work will consider adding multiple compartments.

Physiologically based modelling of dermal absorption and kinetics of consumer-relevant chemicals: A case study with exposure to bisphenol A from thermal paper

Bisphenol A (BPA) is one of the best studied industrial chemicals in terms of exposure, toxicity, and toxicokinetics. This renders it an ideal candidate to exploit the recent advancements in physiologically based pharmacokinetic (PBPK) modelling to support risk assessment of BPA specifically, and of other consumer-relevant hazardous chemicals in general. Using the exposure from thermal paper as a case scenario, this study employed the multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) model available in the Simcyp® Simulator to simulate the dermal toxicokinetics of BPA at local and systemic levels. Sensitivity analysis helped to identify physicochemical and physiological factors influencing the systemic exposure to BPA. The iterative modelling process was as follows: (i) development of compound files for BPA and its conjugates, (ii) setting-up of a PBPK model for intravenous administration, (iii) extension for oral administration, and (iv) extension for exposure via skin (i.e., hand) contact. A toxicokinetic study involving hand contact to BPA-containing paper was used for model refinement. Cumulative urinary excretion of total BPA had to be employed for dose reconstruction. PBPK model performance was verified using the observed serum BPA concentrations. The predicted distribution across the skin compartments revealed a depot of BPA in the stratum corneum (SC). These findings shed light on the role of the SC to act as temporary reservoir for lipophilic chemicals prior to systemic absorption, which inter alia is relevant for the interpretation of human biomonitoring data and for establishing the relationship between external and internal measures of exposure.

Preparation of Certified Methodology for Testing Transdermal Absorption of Chemicals In Vitro

This publication presents the preparation of a certified methodology for in vitro transdermal absorption testing of chemicals and highlights the various pitfalls in their implementation. Vertical diffusion cells (Franz cells) were used to test the dermal absorption of caffeine, benzoic acid, and testosterone across a penetration membrane (porcine ear skin), while the receptor fluid samples were evaluated by HPLC. The designed methodology was certified in 2022 in the Good Laboratory Practice system and will be used at the VUOS Rybitví and at the Medical Faculty of the Charles University in Hradec Králové to assess the dermal absorption of various substances in the environment and occupational surroundings.

Validation of HepG2/C3A Cell Cultures in Cyclic Olefin Copolymer Based Microfluidic Bioreactors.

Organ-on-chip (OoC) technology is one of the most promising in vitro tools to replace the traditional animal experiment-based paradigms of risk assessment. However, the use of OoC in drug discovery and toxicity studies remain still limited by the low capacity for high-throughput production and the incompatibility with standard laboratory equipment. Moreover, polydimethylsiloxanes, the material of choice for OoC, has several drawbacks, particularly the high absorption of drugs and chemicals. In this work, we report the development of a microfluidic device, using a process adapted for mass production, to culture liver cell line in dynamic conditions. The device, made of cyclic olefin copolymers, was manufactured by injection moulding and integrates Luer lock connectors compatible with standard medical and laboratory instruments. Then, the COC device was used for culturing HepG2/C3a cells. The functionality and behaviour of cultures were assessed by albumin secretion, cell proliferation, viability and actin cytoskeleton development. The cells in COC device proliferated well and remained functional for 9 days of culture. Furthermore, HepG2/C3a cells in the COC biochips showed similar behaviour to cells in PDMS biochips. The present study provides a proof-of-concept for the use of COC biochip in liver cells culture and illustrate their potential to develop OoC.

Probiotics as a promising prophylactic tool to reduce levels of toxic or potentially toxic elements in bees

Bees are precious living beings for our planet. Thanks to their essential service of pollination, these insects allow the maintenance of biodiversity and the variety and amount of food available. Unfortunately, we are observing an increasingly devastating reduction of bee families and other pollinating insects for factors related to human activities, environmental pollution, diseases and parasites, compromise of natural habitats, and climate change. We show that probiotics can protect bees from element pollution. We collected bees, beeswax, honey, pollen, and propolis directly from hives in a rural area of central Italy to investigate the content of 41 elements in control (not supplemented with probiotics) and experimental (supplemented with probiotics) groups. Our data show a significantly lower concentration of some elements (Ba, Be, Cd, Ce, Co, Cu, Pb, Sn, Tl, and U) in experimental bees than in control groups, indicating a possible beneficial effect of probiotics in reducing the absorption of chemicals. This study presents the first data on element levels after probiotics have been fed to bees and provides the basis for future research in several activities relating to the environment, agriculture, economy, territory, and medicine.

Contribution of gut bacteria to arsenic metabolism in the first year of life in a prospective birth cohort

Gut bacteria are at the interface of environmental exposures and their impact on human systems, and may alter host absorption, metabolism, and excretion of toxic chemicals. We investigated whether arsenic-metabolizing bacterial gene pathways related to urinary arsenic concentrations. In the New Hampshire Birth Cohort Study, urine and stool samples were obtained at six weeks (n = 186) and one year (n = 190) of age. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB) were quantified in infant urine samples using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Total arsenic exposure (tAs) was summarized as Σ(iAs, MMA, DMA) and log2-transformed. Fecal microbial DNA underwent metagenomic sequencing and the relative abundance of bacterial gene pathways were grouped as KEGG Orthologies (KOs) using BioBakery algorithms. Arsenic metabolism KOs with >80% prevalence were log2-transformed and modeled continuously using linear regression, those with <10% were not evaluated and those with 10–80% prevalence were analyzed dichotomously (detect/non-detect) using logistic regression. In the first set of models, tAs was regressed against KO relative abundance or detection adjusting for age at sample collection and child's sex. Effect modification by delivery mode was assessed in stratified models. In the second set of models, the association between the relative abundance/detection of the KOs and arsenic speciation (%iAs, %MMA, %DMA) was quantified with linear regression. Urinary tAs was associated with the increased relative abundance/detection odds of several arsenic-related KOs, including K16509, an arsenate reductase transcriptional regulator, with stronger associations among six-week-olds than one-year-olds. K16509 was also associated with decreased %MMA and increased %DMA at six weeks and one year. Notably, many associations were stronger among operatively-delivered than vaginally-delivered infants. Our findings suggest associations between arsenic-metabolizing bacteria in the infant gut microbiome and urinary arsenic excretion.