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Toxicity

1033

Human 3D Colon Tissue Model for Toxicity and Microbiome studies

The human colon plays host to a wide variety of microbes living together in an ecosystem. Any damage or injury to the colonic epithelium disturbs this ecosystem which can in turn lead to inflammation and disease. The colonic epithelium is a dynamic structure with a self-renewing capacity and serves as an organ for reabsorption of […]
1029

Assessment of Skin Toxicity in an in Vitro Reconstituted Human Epidermis Model Using Deep Learning

Skin toxicity is a common safety concern associated with drugs that inhibit epidermal growth factor receptors as well as other targets involved in epidermal growth and differentiation. Recently, the use of a three-dimensional reconstructed human epidermis model enabled large-scale drug screening and showed potential for predicting skin toxicity. Although a decrease in epidermal thickness was […]
1022

Ocular side effects of systemic medications: utilization of the 3D human corneal epithelial tissue model

Many systemic medications administered at high doses have the potential to induce unwanted ocular effects, including light sensitivity, pain, or corneal edema that are due to inflammation and/or cytotoxicity. Current drug screening experiments utilize animal models which are not suitable for rapid drug screening, as they have poor species extrapolation, and lack standardization. There is […]
930

Microvesicating effects of sulfur mustard on an in vitro human skin model

Bis-(b-chloroethyl) sulfide (SM) is a potent skin vesicant previously used for chemical warfare. Progress in determination of the mechanistic basis of SM pathology, and development of prophylactic and/or therapeutic countermeasures to SM exposure has been hampered by lack of physiologically relevant models of human skin. The current work evaluated a newly developed tissue engineered full-thickness […]
908

Dicationic Amino Substituted Gemini Surfactants and their Nanoplexes: Improved Synthesis and Characterization of Transfection Efficiency and Corneal Penetration In Vitro

Purpose- To formulate and characterize nanoparticles from m-7NH-m gemini surfactants, synthesized by a new improved method, for non-invasive gene delivery including optimization of composition for transfection efficiency and corneal penetration. Methods – A one-pot, solvent-free, DMAP-free method was developed for the synthesis of m-7NH-m (m=12– 18) gemini surfactant series. Lipoplexes (LPXs) and nanoplexes (NPXs) of […]
879

Development of a Model for Assessment of Blue Light Activated Toxicity in EpiGingival™ and EpiGingival™-FT Tissues

Traditional phototoxicity models examine activation of test material by ultraviolet A (UVA) light. In these models, the ability of a test chemical to induce toxicity in cells or tissues after light exposure is compared to non-light exposed tissues. While UV-induced toxicity is of great concern, it is clear that lower energy light in the blue […]
853

Toxicity of Food Contact Paper Evaluated by Combined Biological and Chemical Methods

The study was focused on assessment of potential health risks of paper-based food contact materials (FCMs) in a step-wise approach using three toxicological bioassays in vitro and chemical analyses of migrating contaminants. 3T3 NRU cytotoxicity test showed high sensitivity to detect basal toxicity of FCMs extracts and served as a firstline test for selection of […]
845

Assessment of Alveolar Toxicity and Fibrotic Potential In Vitro using the Mattek EpiAlveolar™ Model

Pulmonary fibrosis (PF) is a debilitating, typically fatal, condition caused by a variety of factors including environmental or occupational exposures, drugs, radiation, and genetic predisposition. No current in vitro (immortalized cell lines), ex vivo, in silico or in vivo models of PF fully recapitulate all salient features of the human disease. In this study, a […]
841

Hyperosmolal vaginal lubricants markedly reduce epithelial barrier properties in a three-dimensional vaginal epithelium model

Most of the widely used vaginal lubricants in the U.S. and Europe are strongly hyperosmolal, formulated with high concentrations of glycerol, propylene glycol, polyquaternary compounds or other ingredients that make these lubricants 4 to 30 times the osmolality of healthy vaginal fluid. Hyperosmolal formulations have been shown to cause marked toxicity to human colorectal epithelia in vivo, and […]
814

Cytotoxicity of copper (II) oxide nanoparticles in rat and human intestinal cell models

Copper (II) oxide nanoparticles (CuO NPs) have a variety of commercial applications ranging from catalysts to semiconductors. There is a potential for human oral exposure to CuO NPs following accidental or intentional ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. CuO NPs are toxic to aquatic organisms but their mammalian toxicity is less well known. […]
810

Health Safety of Food Contact Paper Evaluated by in vitro Toxicological Methods

Paper and paperboard are widely used as food packaging materials intended for direct contact with foodstuffs and have to comply with a basic set of criteria concerning safety. A number of chemicals, such as slimicides, bleaching agents, and inks are used during the paper production process. Consequently, the total amounts of extractables might be high and the […]
799

In vitro systems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures

Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate with oral preneoplasia, cancer and inflammation (e.g. periodontitis). Alteration of smoking-related gene expression changes in oral epithelial cells is similar to that in bronchial and nasal epithelial cells. Using a systems toxicology approach, we have previously […]
794

Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol

Development of physiologically relevant test methods to analyse potential irritant effects to the respiratory tract caused by e-cigarette aerosols is required. This paper reports the method development and optimisation of an acute in vitro MTT cytotoxicity assay using human 3D reconstructed airway tissues and an aerosol exposure system. The EpiAirway™ tissue is a highly differentiated in vitro human […]
608

SULFUR MUSTARD TOXICITY FOLLOWING DERMAL EXPOSURE: ROLE OF OXIDATIVE STRESS, AND ANTIOXIDANT THERAPY.

Objective:  Sulfur mustard (bis-2-(chloroethyl) sulfide) is a chemical warfare agent (military code: HD) causing extensive skin injury. The mechanisms underlying HD-induced skin damage are not fully elucidated. This review will critically evaluate the evidence showing that oxidative stress is an important factor in HD skin toxicity. Oxidative stress results when the production of reactive oxygen […]
321

CONCORDANCE BETWEEN DIFFERENT IN VITRO CULTURE MODELS DESIGNED TO PREDICT VAGINAL IRRITATION AND/OR TOXICITY.

The safety profile of potential microbicides is equally, if not more important than anti-HIV activity. At the very least, candidates must not impair natural defences against HIV-1 infection or cause inflammation. In this study, researchers at St. George’s Hospital Medical School (UK) and the International Partnership for Microbicides (IPM) investigated the concordance between five different […]
468

PRECLINICAL EVALUATION OF LIME JUICE AS A TOPICAL MICROBICIDE CANDIDATE.

This study by researchers in the CONRAD (Contraceptive Research and Development) Program at Eastern Virginia Medical School and at St. George’s University/London demonstrated how Mattek’s EpiVaginal in vitro human cervico-vaginal tissue equivalent can be used pre-clinically to test potentially cytotoxic microbicide formulations in vitro. Background: The continued growth of the global HIV epidemic highlights the […]
655

IN VITRO EVALUATION OF AIRWAY TOXICITY USING THE EPIAIRWAY ORGANOTYPIC IN VITRO HUMAN AIRWAY MODEL.

Recent REACH legislation has heightened the need for validated in vitro airway toxicity models. However, in vitro determination of airway toxicity potential is problematic since submerged monolayer cell cultures are not amenable to dosing of vapors or water insoluble chemicals. The EpiAirway model is an organotypic air-liquid interface culture produced from normal human airway epithelial […]
566

EVALUATION OF IN VITRO MODELS FOR REACH TOXICITY TESTING: INDUCIBILITY OF XENOBIOTIC METABOLIZING ENZYME (XME) ACTIVITY IN IN VITRO HUMAN AIRWAY (EPIAIRWAY™) AND EPIDERMAL (EPIDERM™) MODELS.

Dermal and airway epithelia contain XMEs including phase I (oxidative) and phase II (conjugative) activities. These XMEs may play a role in biotransformation of drugs and chemicals, leading to altered drug activity or formation of toxic/mutagenic metabolites. Consideration of metabolic activity is therefore important for development of in vitro toxicity/genotoxicty assays required by REACH and […]
580

NON-ANIMAL METHODS FOR TOXICITY TESTING: EMERGING RESEARCH, METHODS & POLICIES.

Areas of emerging skin research include: studies on skin regeneration and the mechanisms involved in skin irritation and wound healing; modifying existing in vitro methods to make them acceptable for a broader range of testing applications; and, development of new methods for in vitro culture of skin cells, including co-cultures (keratinocytes + another type of […]
561

NON-ANIMAL APPROACHES FOR CONSUMER SAFETY RISK ASSESSMENTS: UNILEVER’S SCIENTIFIC RESEARCH PROGRAMME.

Non-animal based approaches to risk assessment are now routinely used for assuring consumer safety for some endpoints (such as skin irritation) following considerable investment in developing and applying new methods over the past 20 years. Unilever’s research programme into non-animal approaches for safety assessment is currently focused on the application of new technologies to risk […]
725

TOPICAL DELIVERY OF SIRNA-BASED SPHERICAL NUCLEIC ACID NANOPARTICLE CONJUGATES FOR GENE REGULATION

Topical application of nucleic acids offers many potential therapeutic advantages for suppressing genes in the skin, and potentially for systemic gene delivery. However, the epidermal barrier typically precludes entry of gene-suppressing therapy unless the barrier is disrupted. We now show that spherical nucleic acid nanoparticle conjugates (SNA-NCs), gold cores surrounded by a dense shell of […]
572

AN IN VITRO HUMAN AIRWAY MODEL FOR RAPID TOXICITY AND FORMULATION SCREENING OF NASAL DRUG DELIVERY SYSTEMS.

INTRODUCTION: Purpose: Nasal delivery of protein and other high molecular weight drugs is an attractive option to injection or oral delivery. However, nasal drug delivery is limited by potential irritation/toxicity issues, difficulties in achieving effective doses and rapidity of clearance from the nasal cavity. These difficulties are best addressed early in formulation development prior to […]
448

IN VITRO AND IN VIVO SCREENING OF INTRANASAL INSULIN FORMULATIONS.

This study by researchers at Nastech Pharmaceuticals demonstrated that Mattek’s EpiAirway in vitro human tissue equivalents can be used by pharmaceutical companies to develop intranasal drug formulations that provide improved permeation in vivo of Active Pharmaceutical Ingredients (API’s). Nasal delivery of insulin provides an attractive option for a non-invasive diabetes treatment. To identify a suitable […]
579

IN VITRO APPROACHES FOR PREDICTING IRRITATION POTENTIAL OF TOPICAL EXPOSURES TO THE SKIN AND EYES.

Outline: Focus on topical exposure toxicity measures …Skin ……Corrosion ……Irritation –Chemicals ……Mildness –Formulations …Eye ……Physiology and modes of action –eye irritation ……Human Reconstructed Tissues ………Ingredients ………Mild formulation assessment …BCOP ……Moderate formulation assessment histology Conclusions: Skin Irritation/Corrosion …Validated methods are in place for testing chemicals for corrosion and irritation (EU). …Methods for determining mildness of formulations […]
649

IL-18 SECRETION AS A MARKER FOR IDENTIFICATION OF CONTACT SENSITIZERS IN THE EPIDERM IN VITRO HUMAN SKIN MODEL.

Assessment of the allergic potential of chemicals has traditionally been conducted in animal models such as the local lymph node assay (LLNA). However, recent legislation has prohibited the use of animals for conducting such tests on cosmetics or cosmetic ingredients. Thus, animal alternative tests for contact sensitization are urgently needed. Interluekin-18 (IL-18) secretion has recently […]
775

SAFETY EVALUATION OF NANOSILVER USING RECONSTRUCTED HUMAN GIT TISSUES

In our pilot study focused on safety evaluation of nanosilver three novel commercially available  reconstructed human  tissues were used for mimicking the human gastrointestinal tract (GIT). The evaluated endpoints included tissue viability, cytokine release and penetration of silver into the tissue culture medium. The results confirmed no adverse effect of nanosilver on the viability of […]
567

XENOBIOTIC METABOLISM GENE EXPRESSION IN THE EPIDERM™ IN VITRO 3D HUMAN EPIDERMIS MODEL COMPARED TO HUMAN SKIN.

There is an urgent need to validate in vitro human skin models for use in safety testing. An important component of validation is characterizing the metabolizing capacity of these models. We report comparison of the expression of 139 genes encoding xenobiotic metabolizing enzymes in the EpiDerm™ model and human skin. In microarray analysis, the expression […]
680

NVC-422: TOWARDS DEVELOPING PRECLINICAL INFECTED TISSUE MODELS.

Background: P. aeruginosa and S. aureus are opportunistic human pathogens implicated in many clinical diseases of the eye and skin, including keratitis and impetigo, respectively. Infection can involve destruction of underlying tissue by toxins to exacerbate tissue damage, leading to erosive disease. Developing infected tissue models provide a platform for assessing antimicrobial efficacy and toxicity […]