Genotoxicity

Micronucleus Induction by 5-Methoxypsoralen in the Photo Reconstructed Skin Micronucleus Assay: Development of a Human-Relevant NAM for Identifying Photo-genotoxic Substances

To address a lack of suitable non-animal tools to screen novel ingredients in personal care products for mutagenic/clastogenic activity after solar light exposure, we initiated a three-phase program to develop […]

Qualification of the human Reconstructed Intestine Micronuclei Cytome assay for site-of-contact genotoxic hazard identification

While valuable for hazard identification, in vitro genotoxicity tests that are conducted in 2D monolayer cell cultures possess limitations to accurately envisage in vivo outcomes and may result in unnecessary […]

Assessing nanotoxicity of food-relevant particles: A comparative analysis of cellular responses in cell monolayers versus 3D gut epithelial cultures

Engineered nanoparticles (NPs) are extensively used in the food industry, yet safety concerns remain. The lack of validated methodologies is a bottleneck towards resolving this uncertainty. Hence, the current study […]

Reconstructed human intestinal comet assay, a possible alternative in vitro model for genotoxicity assessment

The aim of the present study was to evaluate the compatibility of reconstructed 3D human small intestinal microtissues to perform the in vitro comet assay. The comet assay is a […]

Development of a micronucleus test using the EpiAirway™ organotypic human airway model

The use of organotypic human tissue models in genotoxicity has increased as an alternative to animal testing. Genotoxicity is generally examined using a battery of in vitro assays such as […]

Proteomic, Metabolomic, and Lipidomic Analyses of Lung Tissue Exposed to Mustard Gas

Sulfur mustard (HD) poses a serious threat due to its relatively simple production process. Exposure to HD in the short-term causes an inflammatory response, while long-term exposure results in DNA […]

Organotypic 3D primary human nasal tissue model for toxicological studies

The nasal mucosa serves as the first line of defense against inhaled chemicals, drugs, and respiratory infections. Here we developed a novel in vitro primary human cell-based 3D human nasal […]

Development of reconstructed intestinal micronucleus cytome (RICyt) assay in 3D human gut model for genotoxicity assessment of orally ingested substances

The micronucleus (MN) assay is widely used as part of a battery of tests applied to evaluate the genotoxic potential of chemicals, including new food additives and novel food ingredients. […]

Use of the EpiDerm 3D reconstructed skin micronucleus assay for fragrance materials

In order to evaluate the utility of the 3D reconstructed skin micronucleus assay (3DRSMN) to assess clastogenic/aneugenic potential of the fra- grance chemicals, a set of 22 fragrance materials were […]

Small Molecule IL-36γ Antagonist as a Novel Therapeutic Approach for Plaque Psoriasis

IL-36 cytokines are pro-inflammatory members of the IL-1 family that are upregulated in inflammatory disorders. Specifically, IL-36γ is highly expressed in active psoriatic lesions and can drive pro inflammatory processes […]

The 3D reconstructed skin micronucleus assay using imaging flow cytometry and deep learning: A proof-of-principle investigation

The reconstructed skin micronucleus (RSMN) assay was developed in 2006, as an in vitro alternative for genotoxicity evaluation of dermally applied chemicals or products. In the years since, significant progress […]

Experiments in the EpiDerm 3D Skin In Vitro Model and Minipigs In Vivo Indicate Comparatively Lower In Vivo Skin Sensitivity of Topically Applied Aneugenic Compounds

Risk management of in vitro aneugens for topically applied compounds is not clearly defined because there is no validated methodology to accurately measure compound concentration in proliferating stratum basale keratinocytes […]

Validation of the 3D reconstructed human skin micronucleus (RSMN) assay: an animal-free alternative for following-up positive results from standard in vitro genotoxicity assays

In vitro test batteries have become the standard approach to determine the genotoxic potential of substances of interest across industry sectors. While useful for hazard identification, standard in vitro genotoxicity […]

The 3D reconstructed skin micronucleus assay: considerations for optimal protocol design

Implementation of the seventh amendment to the EU Cosmetics Directive has driven much research into suitable in vitro alternative assays to support satisfactory risk assessments. One such assay is the […]

Evaluating the Inflammatory and Genotoxic Effects of Smokeless Tobacco Using a Human Organotypic Model of Oral Epithelium

In addition to the well-known effects of tobacco use on the causation of lung and cardiovascular disease, tobacco use is also implicated as a major cause of oral cavity disease […]

Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™)

Background: The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for […]

Validation of the In Vitro Reconstructed Skin Micronucleus Assay as a Potential Animal Alternative for Fragrance Materials

The in vitro reconstructed skin micronucleus assay is a skin-based assay which measures the clastogenicity and aneugenicity potential of chemical materials and mixtures. Reconstructed skin models are prepared from primary human cells and […]

The EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay: Historical control data and proof of principle studies for mechanistic assay adaptations

The in vitro human reconstructed skin micronucleus (RSMN) assay in EpiDerm is a promising novel animal alternative for evaluating genotoxicity of topically applied chemicals. It is particularly useful for assessing […]

FORSKOLIN PROTECTS KERATINOCYTES FROM UVB-INDUCED APOPTOSIS AND INCREASES DNA REPAIR INDEPENDENT OF ITS EFFECTS ON MELANOGENESIS.

This study by researchers in the Laboratory of Cell Biology, National Cancer Institute (National Institutes of Health) demonstrated that Mattek’s melanocyte/keratinocyte-containing MelanoDerm in vitro human skin tissue equivalent can be […]

UPDATE ON VALIDATION STATUS AND INDUSTRY UTILIZATION OF NORMAL HUMAN 3D (NHU-3D) ANIMAL ALTERNATIVE MODELS.

Progress in in vitro tissue engineering over the last several decades has contributed to a significant decrease in animal use for industrial risk and safety assessment of products and ingredients. […]

COLIPA VALIDATION OF THE RECONSTRUCTED HUMAN SKIN MICRONUCLEUS ASSAY (RSMN): A NOVEL MICRONUCLEUS ASSAY IN A 3D HUMAN SKIN MODEL.

This COLIPA-funded study by scientists at Procter and Gamble, Henkel AG and Co KGaA, L’Oreal, the Institute for In Vitro Sciences (IIVS), Unilever, Beiersdorf AG, KPSS (Kao Professional Salon Services), […]

ANALYSIS OF IONIZING RADIATION-INDUCED DNA DAMAGE AND REPAIR IN THREE-DIMENSIONAL HUMAN SKIN MODEL SYSTEM.

This study by researchers in the Columbia University College of Physicians and Surgeons Center for Radiological Research demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent and EpiDermFT […]

LONG-TERM BIOLOGICAL BYSTANDER EFFECTS OF MICROBEAM IRRADIATION IN 3D HUMAN TISSUE MODELS.

This study by researchers at the National Cancer Institute (NIH), University of Lethbridge (Canada) and Columbia University demonstrated that Mattek’s EpiDermFT and EpiAirway in vitro human tissue equivalents exhibited the […]

THE DEVELOPMENT OF AN IN VITRO SCREENING STRATEGY FOR TOPICALLY APPLIED PRODUCTS.

The objective of this study was the pharmaco-toxicological understanding of the constituents of an authenticated herbal mixture. The mixture was prepared by maceration in ethanol and subsequent dilution to produce […]

DERMAL PENETRATION AND METABOLISM OF p-AMINOPHENOL AND p-PHENYLENEDIAMINE: APPLICATION OF THE EPIDERM HUMAN RECONSTRUCTED EPIDERMIS MODEL.

This study by scientists at Procter & Gamble Co. demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent showed excellent correlation to in vivo results for skin penetration and […]

RECONSTITUTED 3-DIMENSIONAL HUMAN SKIN AS A NOVEL IN VITRO MODEL FOR STUDIES OF CARCINOGENESIS.

EpiDerm (Mattek Co., MA) is a reconstituted human skin equivalent which exhibits morphological and growth characteristics similar to human skin. This model has previously been utilized to evaluate the cytotoxicity […]

STUDIES OF BYSTANDER EFFECTS IN ARTIFICIAL HUMAN 3D TISSUE SYSTEMS USING A MICROBEAM IRRADIATION.

According to the target theory of radiation-induced effects (1), a central tenet of radiation biology, DNA damage occurs during or very shortly after irradiation of the nuclei in targeted cells, […]

THE COLIPA STRATEGY FOR THE DEVELOPMENT OF IN VITRO ALTERNATIVES: GENOTOXICITY.

This report by the COLIPA Genotoxicity Task Force, comprised of researchers from Wella AG, L’Oreal, Procter & Gamble, Henkel, and Unilever, presents details of a concept developed for testing dermally […]

CHARACTERIZATION OF THE EPIDERM™ HUMAN 3-D SKIN MODEL FOR GENOTOXICITY TESTING.

This study by scientists at Procter & Gamble, the Institute for In Vitro Sciences (IIVS) and Mattek Corp. demonstrated that a micronucleus assay based on Mattek’s EpiDerm in vitro human […]

DEVELOPMENT OF A NOVEL MICRONUCLEUS ASSAY USING THE HUMAN 3-D SKIN MODEL, EPIDERM™.

This study by scientists at Procter & Gamble Co. and the Institute for In Vitro Sciences (IIVS) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent […]

DEVELOPMENT OF A MICRONUCLEUS ASSAY IN THE EPIDERM HUMAN 3D SKIN MODEL.

This study by scientists at Procter & Gamble Co. and the Institute for In Vitro Sciences (IIVS) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent […]

FURTHER DEVELOPMENT OF A MICRONUCLEUS ASSAY USING THE HUMAN 3-D SKIN MODEL, EPIDERM™.

INVESTIGATION OF THE BIOTRANSFORMING CAPACITY OF HUMAN RECONSTRUCTED SKIN MODELS FOR GENOTOXICITY TESTING.

Skin penetration is a route of xenobiotic uptake in the body, however, less information is available about the fate of the penetrated xenobiotic in regard of metabolic turn over. The […]

METABOLICALLY COMPETENT HUMAN SKIN MODELS: ACTIVATION AND GENOTOXICITY OF BENZO[A]PYRENE.

The polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) is metabolized into a complex pattern of BP derivatives, among which the ultimate carcinogen (+)-anti-BP-7,8-diol-9,10- epoxide (BPDE) is formed to certain extents. Skin […]

EVALUATION OF XENOBIOTIC METABOLISM IN HUMAN RECONSTRUCTED SKIN MODELS FOR GENOTOXICITY TESTING.

Skin penetration and absorption is a major route of xenobiotic uptake. Skin maintains furthermore capacities to transform chemical substances which was previously shown by transcriptional expression analysis of metabolizing enzymes […]

DNA DOUBLE-STRAND BREAKS FORM IN BYSTANDER CELLS AFTER MICROBEAM IRRADIATION OF THREE-DIMENSIONAL HUMAN TISSUE MODELS.

This study by researchers at the National Cancer Institute (NIH), University of Lethbridge (Canada) and Columbia University demonstrated the ability to use Mattek’s EpiDermFT and EpiAirway in vitro human tissue […]

COMPARATIVE STUDIES ON THE BIOTRANSFORMATION OF BENZO[A]PYRENE IN HUMAN KERATINOCYTES, IN VITRO SKIN MODELS, AND SKIN EX VIVO: METABOLITE PATTERNS AS INDICATOR FOR THE METABOLIC CAPACITY OF SKIN EQUIVALENTS.

In vitro skin models are increasingly important for toxicological testing strategies to facilitate risk assessment and classification of chemicals. The reliability of these tests depends on the capacity of skin […]

A TIERED APPROACH TO THE USE OF ALTERNATIVES TO ANIMAL TESTING FOR THE SAFETY ASSESSMENT OF COSMETICS: GENOTOXICITY. A COLIPA ANALYSIS.

For the assessment of genotoxic effects of cosmetic ingredients, a number of well-established and regulatory accepted in vitro assays are in place. A caveat to the use of these assays […]

IMPROVING GENOTOXICITY TESTING: COMET ASSAY WITH 3D SKIN MODELS.

This study by scientists at Henkel, ECVAM, TNO, L’Oreal, COLIPA, Procter and Gamble – Cosmital SA, Unilever, Procter and Gamble US, Beiersdorf, KPSS (Kao Professional Salon Services), GlaxoSmithKline (GSK) and […]

AUTOMATION AND VALIDATION OF MICRONUCLEUS DETECTION IN THE 3D EPIDERM™ HUMAN RECONSTRUCTED SKIN ASSAY AND CORRELATION WITH 2D DOSE RESPONSES.

Recent restrictions on the testing of cosmetic ingredients in animals have resulted in the need to test the genotoxic potential of chemicals exclusively in vitro prior to licensing. However, as […]

FURTHER DEVELOPMENT OF THE EPIDERM 3D RECONSTRUCTED HUMAN SKIN MICRONUCLEUS (RSMN) ASSAY.

This study by scientists at Procter & Gamble Co., the Institute for In Vitro Sciences (IIVS), Advanced Testing Laboratory and Mattek Corp. demonstrated that an in vitro human reconstructed skin […]

COLIPA VALIDATION OF THE RECONSTRUCTED HUMAN SKIN MICRONUCLEUS ASSAY (RSMN): FURTHER PRE-VALIDATION STUDIES AND INVESTIGATIONS IN INCREASING TIME EFFICIENCY.

The European Cosmetics Association (COLIPA) has initiated a multi-laboratory project to establish and evaluate more predictive in vitro genotoxicity assays using 3D human tissues as replacements for current mammalian cell […]

INTRALABORATORY AND INTERLABORATORY EVALUATION OF THE EPIDERM 3D HUMAN RECONSTRUCTED SKIN MICRONUCLEUS (RSMN) ASSAY.

This study by scientists at Procter & Gamble Co., the Institute for In Vitro Sciences (IIVS), Advanced Testing Laboratory and Mattek Corp. demonstrated that an in vitro human reconstructed skin […]

THE USE OF 3D SKIN MODELS IN THE MICRONUCLEUS AND COMET ASSAYS: FURTHER PRE-VALIDATION STUDIES AND INVESTIGATIONS INTO INCREASING THROUGHPUT.

The European Cosmetic Association (COLIPA) has initiated a multi-laboratory project to establish and evaluate more predictive in vitro genotoxicity assays using 3D human tissues as replacements for current mammalian cell […]

GENOTOXICITY TESTING USING THE MICRONUCLEUS ASSAY IN THE EPIDERM™ HUMAN 3D SKIN MODEL.

This study by scientists at Procter & Gamble, the Institute for In Vitro Sciences (IIVS), and Mattek Corp. demonstrated that the Micronucleus Assay that utilizes Mattek’s EpiDerm in vitro human […]

THE USE OF HUMAN 3D EPIDERMAL MODELS FOR GENOTOXICITY TESTING: RESULTS WITH THE COMET ASSAY.

EU policy, including REACH and the Cosmetics Directive, implies the urgent need for reliable in vitro strategies with regards to the safety evaluation of chemicals. Currently used in vitro assays […]

USE OF THE COMET ASSAY TO DETECT GENOTOXIC EFFECTS IN RECONSTITUTED HUMAN SKIN.

This study by scientists at Procter & Gamble and Wella-Cosmital SA demonstrated that Mattek’s EpiDerm in vitro human tissue equivalent may provide an excellent platform for performing comet (genotoxicity) assays […]

THE RECONSTRUCTED SKIN COMET ASSAY SHOWS GOOD INTRA- AND INTER-LABORATORY REPRODUCIBILITY: RESULTS FROM THREE LABORATORIES.

EU policy marks the need for a broad replacement of animal tests in relation to the 7th Amendment to the Cosmetics Directive. For cosmetics ingredients as well as many chemicals, […]

IN VITRO GENOTOXICITY TESTING USING THE MICRONUCLEUS ASSAY IN CELL LINES, HUMAN LYMPHOCYTES AND 3D HUMAN SKIN MODELS.

The toxicological relevance of the micronucleus (MN) testis well defined: it is a multi-target genotoxic endpoint,assessing not only clastogenic and aneugenic events butalso some epigenetic effects, which is simple to […]

THE RECONSTRUCTED SKIN MICRONUCLEUS ASSAY (RSMN) IN EPIDERM™: DETAILED PROTOCOL AND HARMONIZED SCORING ATLAS.

The European Cosmetic Toiletry and Perfumery Association (COLIPA), along with contributions from the European Centre for the Validation of Alternative Methods (ECVAM), initiated a multi-lab international prevalidation project on the […]

γ-H2AX FORMATION IN THREE-DIMENSIONAL HUMAN SKIN AND CELL MODELS FOLLOWING INVITRO EXPOSURE TO SULFUR MUSTARD.

Sulfur mustard (2-2’-dichlorodiethyl sulfide, SM) is a cytotoxic chemical warfare agent known for its vesicating properties. SM exposure to human tissue results in DNA damage, eventually leading to cell and […]

CHARACTERIZATION OF ENZYME ACTIVITIES OF CYTOCHROME P450 ENZYMES, FLAVIN-DEPENDENT MONOOXYGENASES, N-ACETYLTRANSFERASES AND UDP-GLUCURONYLTRANSFERASES IN HUMAN RECONSTRUCTED EPIDERMIS AND FULL-THICKNESS SKIN MODELS.

With the perspective to use human reconstructed skin models for genotoxicity testing which require metabolic activation of xenobiotics, this study aimed to characterize activities of biotransforming enzymes within two human […]

ASSESSMENT OF AIRWAY GENOTOXICITY POTENTIAL USING THE EPIAIRWAY IN VITRO HUMAN AIRWAY MODEL AND THE COMET ASSAY.

Determination of genotoxic potential is an important consideration for safety assessment of chemicals that may be inhaled following exposure to consumer products, occupational chemicals or environmental pollutants.   Commonly used in […]

GENOTOXICITY TESTING USING THE NORMAL HUMAN CELL BASED 3D EPITHELIAL MODELS.

Safety assessment of new products for human use requires genotoxicity testing to ensure their non-carcinogenicity. Current in vitro genotoxicity assays have low specificity resulting in unacceptably high rates of false […]

The Cosmetics Europe strategy for animal-free genotoxicity testing: project status up-date

The Cosmetics Europe (formerly COLIPA) Genotoxicity Task Force has driven and funded three projects to help address the high rate of misleading positives in in vitro genotoxicity tests: The completed […]