Irritation

Development of Sensitive In Vitro Protocols for the Biocompatibility Testing of Medical Devices and Pharmaceuticals Intended for Contact with the Eyes: Acute Irritation and Phototoxicity Assessment

This study introduces a novel in vitro methodology that employs the 3-D reconstructed tissue model, EpiOcular, to assess the irritation and phototoxicity potential of medical devices and drugs in contact with the eye. Our study evaluated diverse test materials, including medical devices, ophthalmological solutions and an experimental drug (cemtirestat), for their potential to cause eye […]

Vaginal irritation testing—prospects of human organotypic vaginal tissue culture models

Personal lubricants intended for local or systemic delivery via the vaginal route can induce vaginal irritation, damage the vaginal epithelial barrier which can enhance microbial entry, induce infammation, and alter the microbiome of the vaginal ecosystem. Therefore, manufacturers of personal lubricants and medical devices are required to show biocompatibility and safety assessment data to support […]

In Vitro Irritation Assay and Regulatory Acceptance Two Years after ISO 10993-23:2021 Release

Medical device biological safety testing is transitioning away from the use of animals to more technologically advanced and reliable in vitro alternative methods. The irritation potential of medical devices has historically been evaluated by rabbit testing; however, ISO 10993-23:2021 offers a validated alternative by using reconstructed human epidermis (RhE) as the first consideration. Regulatory agencies […]

Pre-validation of an in vitro skin irritation test for medical devices using the reconstructed human tissue model EpiDerm™

Assessment of dermal irritation is an essential component of the safety evaluation of medical devices. Reconstructed human epidermis (RhE) models have replaced rabbit skin irritation testing for neat chemicals and their mixtures (OECD Test Guideline 439). However, this guideline cannot be directly applied to the area of medical devices (MD) since their non-toxicity assessment is […]

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 […]

Infection and Replication of Influenza Virus at the Ocular Surface

Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell […]

CON4EI: CONsortium for in vitro Eye Irritation testing strategy – EpiOcular™ time-to-toxicity (EpiOcular ET-50) protocols for hazard identification and labeling of eye irritating chemicals

Assessment of acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. The objective of the CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for eye irritation assessment for all drivers of classification. A set of 80 reference chemicals (38 liquids and […]

In Vitro Skin Models and Their Predictability in Defining Normal and Disease Biology, Pharmacology, and Toxicity

In vitro skin model systems are increasingly being used both in the early evaluation of therapeutic drug candidates and in confirmatory mechanistic studies. The most commonly used of these in vitro model systems are reconstituted human epidermis (RHE) models. These RHE skin models consist solely of epidermal keratinocytes, which comes with some limitations but also with the advantage […]

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. […]

Eye irritation testing of nanomaterials using the EpiOcular™ eye irritation test and the bovine corneal opacity and permeability assay

Background: Assessment of eye irritation hazard has long been a core requirement in any chemical legislation. Nevertheless, publications focusing on the eye damaging potential of nanomaterials are scarce. Traditionally, eye irritation testing was performed using rabbits. The OECD Test Guideline 437 Bovine Corneal Opacity and Permeability (BCOP) test method allows determining severely irritating substances without animals, and the […]

Application of Mattek In Vitro Reconstructed Human Skin Models for Safety, Efficacy Screening, and Basic Preclinical Research

During the past three decades, great progress has been achieved in the development of in vitro reconstructed human epidermal (RhE) tissue models. This technology is now available via various manufacturers of commercially available tissue models, and has provided opportunities for researchers worldwide to reduce or even completely avoid in vivo experimentation for screening and prediction of cutaneous […]

Antibacterial modification of an injectable, biodegradable, non-cytotoxic block copolymer-based physical gel with body temperature-stimulated sol-gel transition and controlled drug release

Biomaterials are being extensively used in various biomedical fields; however, they are readily infected with microorganisms, thus posing a serious threat to the public health care. We herein presented a facile route to the antibacterial modification of an important A-B-A type biomaterial using poly (ethylene glycol) methyl ether (mPEG)- poly(-caprolactone) (PCL)-mPEG as a typical model. […]

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 […]

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 […]

EPIVAGINAL TISSUE MODEL FOR PRECLINICAL SCREENING OF SINGLE OR REPEAT EXPOSURE TO VAGINALLY APPLIED CHEMICALS/FORMULATIONS.

A predictive test system for assessing the vaginal irritation potential of chemicals and formulations will have far reaching application in the testing of feminine care products. The vaginal mucosa is commonly exposed to chemicals and therapeutic agents that may result in irritation/inflammation which can make women susceptible to infections such as HIV-1 and HSV-2. Hence, […]

ENHANCED ANTIVIRAL ACTIVITY OF ACYCLOVIR LOADED INTO NANOPARTICLES.

The activity of antivirals can be enhanced by their incorporation in nanoparticulate delivery systems. Peculiar polymeric nanoparticles, based on a β-cyclodextrin-poly (4-acryloylmorpholine) monoconjugate (β-CD-PACM), are proposed as acyclovir carriers. The experimental  procedure  necessary to obtain the acyclovir-loaded nanoparticles  using  the  solvent displacement  preparation  method   will be described   in  this  chapter.   Fluorescent labeled   nanoparticles are prepared […]

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 […]

ORGANOTYPIC HUMAN VAGINAL-ECTOCERVICAL TISSUE MODEL FOR IRRITATION STUDIES OF SPERMICIDES, MICROBICIDES, AND FEMININE-CARE PRODUCTS.

This study by scientists at Boston University School of Medicine and Mattek Corp. demonstrated that Mattek’s EpiVaginal in vitro human cervico-vaginal tissue equivalent is a highly reproducible, non-animal means to assess the irritation potential of topically applied contraceptives, microbicides and vaginal care products. EpiVaginal, a three-dimensional organotypic vaginal-ectocervical (VEC) tissue model, has been developed to […]

AN IN VITRO MODEL OF HUMAN AIRWAY EPITHELIUM (EPIAIRWAY) FOR IN VITRO METABOLISM, TOXICITY SCREENING AND DRUG DELIVERY APPLICATIONS.

This study by Mattek Corp. scientists demonstrated that the EpiAirway in vitro human tracheal/bronchial tissue equivalent possesses the in vivo-like physical and biochemical attributes necessary for evaluating the delivery of drugs, metabolism, airway irritation, and toxicity potential of environmental/occupational chemicals. In vitro airway models are urgently needed as alternatives to animal testing for compliance with […]

HUMAN VAGINAL-ECTOCERVICAL TISSUE MODEL FOR MICROBICIDE IRRITATION STUDIES.

Infection through the vaginal-ectocervical (VEC) tissue is believed to be the main route for the heterosexual transmission of the human immunodeficiency virus (HIV) in women. Recently, a tissue culture-based model of the VEC (EpiVaginal) has been developed. Normal, human VEC epithelial and dendritic cell co-cultures were used to form a three-dimensional tissue using specially formulated […]

HUMAN TISSUE MODEL FOR VAGINAL IRRITATION STUDIES.

Recently, EpiVaginal™, a tissue culture-based model of the vaginal epithelium, has been developed. Normal, human ectocervico-vaginal (ECV) epithelial cells were induced to form a three-dimensional tissue using specially formulated serum free medium. The in vitro tissue reproduces many of the histological, ultrastructural, and protein expression properties of native tissue, including a multilayered three-dimensional morphology, inter-digitation […]

SAFETY STUDY OF AN ANTIMICROBIAL PEPTIDE LACTOCIN 160, PRODUCED BY THE VAGINAL LACTOBACILLUS RHAMNOSUS.

This study by researchers at the Royal Institute of Technology (Sweden), Rutgers University, Rush Medical Center, Health Promoting Naturals, Inc., and The Women’s Hospital of Texas demonstrated the ability to use Mattek’s EpiVaginal in vitro human organotypic vaginal-ectocervical tissue model to determine the irritation potential of an antimicrobial peptide. Purpose: To evaluate the safety of […]

HUMAN VAGINAL—ECTOCERVIAL TISSUE MODEL TO TEST THE IRRITATION POTENTIAL OF CONTRACEPTIVE AND VAGINAL-CARE PRODUCTS.

DEVELOPMENT OF AN IN VITRO ALTERNATIVE ASSAY METHOD FOR VAGINAL IRRITATION.

The vaginal mucosa is commonly exposed to chemicals and therapeutic agents that may result in irritation and/or inflammation. In addition to acute effects, vaginal irritation and inflammation can make women more susceptible to infections such as HIV-1 and herpes simplex virus 2 (HSV-2). Hence, the vaginal irritation potential of feminine care formulations and vaginally administered […]

PRE-VALIDATION OF RECONSTRUCTED EPIVAGINAL TISSUE MODEL TO SCREEN IRRITATION POTENTIAL OF CHEMICALS.

ASSAY DEVELOPMENT FOR IN VITRO EVALUATION OF INHALATION 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 […]

A HIGH-THROUGHPUT IN VITRO MODEL OF HUMAN TRACHEAL/ BRONCHIAL EPITHELIUM (EPIAIRWAY™) FOR PRE-CLINICAL SAFETY AND EFFICACY TESTING OF PHARMACEUTICALS.

This study by scientists at Mattek Corp. demonstrated that Mattek’s EpiAirway in vitro 3-D human tracheal/bronchial tissue equivalent can be produced in a 96-well high-throughput microwell plate format in a highly reproducible manner, enabling the use of this format for in vitro irritation/toxicity screening, high content cell and molecular biology assays, as well as drug […]

INHIBITION OF CRYSTALLIZATION IN DRUG-IN-ADHESIVE-TYPE TRANSDERMAL PATCHES.

In this study the ability of various additives to inhibit crystallization of two model drugs, captopril and levonorgestrel, in acrylate and silicone adhesives was investigated. Among the various additives tested, PVP was found to be the most effective in inhibiting the crystallization of both drugs. Incorporation of PVP in patches (PVP stabilized patches) allowed incorporation […]

OPTIMISATION OF THE EPIDERM TEST PROTOCOL FOR THE UPCOMING ECVAM VALIDATION STUDY ON IN VITRO SKIN IRRITATION TESTS.

*An ECVAM-funded prevalidation study (PV) was conducted during 1999 and 2000 to identify in vitro tests capable of reliably distinguishing between skin irritants (I) and non-irritants(NI) according to European Union risk phrases (“R38” or no classification). The tests evaluated were EpiDerm™, EPISKIN™, PREDISKIN™, the non-perfused pig ear method, and the mouse skin integrity function test […]

INITIAL CHARACTERIZATION OF A NEW MODEL FOR DERMAL IRRITANCY TESTING.

A model of the human epidermis, EpiDerm™, based on neonatal foreskin-derived normal human epidermal keratinocytes (NHEK) has recently been introduced by Mattek Corporation. Cultured using serum free media in easily handled Millicell® CM (Millipore Corp.) cell culture inserts, the model allows application of liquid and solid test materials (potential dermal irritants) directly to the apical […]

NEW EPIDERMAL MODEL FOR DERMAL IRRITANCY TESTING.

A model of the human epidermis, EpiDerm™, based on neonatal, foreskin-derived normal human epidermal keratinocytes (NHEK) has been developed over the past 18 months at Mattek Corporation. Cultured in easily handled Millicell® CM (Millipore Corp.) cell culture inserts, the model allows application of liquid and solid test materials (potential dermal irritants) directly to the stratum […]

SAFETY TESTING OF REMERGENT™ SKINCARE PRODUCTS.

Remergent products are manufactured by AGI Dermatics under rigorous quality control procedures to ensure safety. Testing begins with the important functional ingredients, which are subjected to the most stringent tests in the industry. The finished Remergent products were subjected to safety testing by two in vitro tests to screen for dermal and ocular irritancy, and […]

ORGANOTYPIC HUMAN ORAL TISSUE MODELS FOR EVALUATION OF ORAL CARE PRODUCTS.

Oral irritation can result from exposure of the soft tissue to dentifrice and oral rinse formulations. In vitro tissue models (Mattek Corporation) produced from normal human oral keratinocytes were exposed to common oral care excipients, dentifrice supernatants and mouth rinses to determine the potential irritation of oral care excipients/formulations, including SLS, poloxamer, NaF dentifrice, and […]

IN VITRO SAFETY PROFILE OF PERSONAL CARE PRODUCTS – USE OF AN IN VITRO TESTING PLATFORM BASED ON A RECONSTRUCTED VAGINAL TISSUE MODEL

One of the common goals of industry is to confirm the safety of their products. Ethical concerns have led to the use of alternative testing methods in lieu of traditional testing methods. Several studies have shown good correlation between alternative test methods, traditional testing methods and human exposure. In the current study, the safety profile […]

VAGINAL FORMULATION – HOW INNOCUOUS ARE THEY TO THE VAGINAL EPITHELIAL IMMUNE FUNCTION?

This study by researchers in the Harvard Medical School Dept. of Obstetrics and Gynecology demonstrated that Mattek’s EpiVaginal in vitro human cervico-vaginal tissue equivalent is an excellent tissue model for performing both immunoinflammatory characterization and safety assessment of vaginal products. Problem: The disruption of the epithelial barrier and activation of inflammatory pathways may lead to […]

IRRITATION TESTING OF CONTRACEPTIVE AND FEMININE-CARE PRODUCTS USING EPIVAGINAL, AN IN VITRO HUMAN VAGINAL-ECTOCERVICAL TISSUE MODEL.

ORGANOTYPIC HUMAN ORAL TISSUE MODELS FOR TOXICOLOGICAL STUDIES.

This study by researchers at Procter & Gamble Co., the University of Iowa and Mattek Corp. demonstrated that Mattek’s EpiOral and EpiGingival human oral cavity tissue equivalents can be used to screen the irritation potential of newly developed oral care products and will be useful to study the innate immunity, biology and pathology of the […]

PSORIASIN (S100A7) IS A MAJOR ANTIMICROBIAL COMPONENT OF THE FEMALE GENITAL TRACT.

This study by researchers at the Medical University of Vienna and University Hospital Schleswig-Holstein demonstrated that Mattek’s EpiVaginal in vitro 3-D human cervico-vaginal tissue equivalent can be used to confirm psoriasin expression when the tissue was exposed to IL-1alpha and to secreted components of E. coli. Psoriasin has been shown to be the major Escherichia […]

SPERMICIDAL ACTIVITY OF THE SAFE NATURAL ANTIMICROBIAL PEPTIDE SUBTILOSIN.

This study by researchers at Rutgers University, Rush University Medical Center, The Royal Institute of Technology, Health Promoting Naturals, Inc., and The Women’s Hospital of Texas demonstrated that Mattek’s EpiVaginal in vitro human cervico-vaginal tissue equivalent can be used to accurately mimic the results of prolonged exposure of novel compounds to this human tissue type […]

FOLLOW-UP TO THE ECVAM PREVALIDATION STUDY ON IN VITRO TESTS FOR ACUTE SKIN IRRITATION.

The European Centre for the Validation of Alternative Methods (ECVAM) Skin Irritation Task Force was established in 1996, to review the status of the development and validation of alternative tests for skin irritation and corrosion, and to identify appropriate non-animal tests for predicting human skin irritation that were sufficiently well-developed to be prevalidated and validated […]

ASSESSMENT OF SKIN ABSORPTION AND METABOLISM OF ARACHIDONIC ACID & GLYCERYL ARACHIDONATE USING IN VITRO DIFFUSION CELL TECHNIQUES.

Arachidonic acid (AA), has been used in cosmetics as a surfactant-cleansing and emulsifying agent. Glyceryl arachidonate (GA), a skin conditioning agent and emollient, may be partially metabolized by ester hydrolysis in skin to AA. Based on the Cosmetic Ingredient Review (CIR) Panel’s concern that there was a lack of dermal absorption data for AA, in […]