Human relevance of in vivo and in vitro skin irritation tests for hazard classification of pesticides.

Test methods to inform hazard characterization and labeling of pesticides to protect human health are typically conducted using laboratory animals, and for skin irritation/corrosion the rabbit Draize test is currently required by many regulatory agencies. Although the Draize test is generally regarded to provide protective classifications for human health, new approach methodologies (NAMs) have been developed that offer more human relevant models that circumvent the uncertainty associated with species differences that exist between rabbits and humans. Despite wide applicability and use of these test methods across a broad range of chemicals, they have not been widely adopted for testing pesticides and pesticidal formulations.

Promoting New Approach Methodologies (NAMs) for research on skin color changes in response to environmental stress factors: tobacco and air pollution.

Aging is one of the most dynamic biological processes in the human body and is known to carry significant impacts on individuals' self-esteem. Skin pigmentation is a highly heritable trait made possible by complex, strictly controlled cellular and molecular mechanisms. Genetic, environmental and endocrine factors contribute to the modulation of melanin's amount, type and distribution in the skin layers.

Evaluation of a tiered in vitro testing strategy for assessing the ocular and dermal irritation/corrosion potential of pharmaceutical compounds for worker safety.

Introduction: Irritation reactions are a frequently reported occupational illness. The potential adverse effects of pharmaceutical compounds (PCs) on eye and skin can now be assessed using validated in vitro methods.

Objectives: Our overall aim is to reduce animal testing by replacing the historically utilized in vivo test methods with validated in vitro test methods which accurately determine the ocular and dermal irritation/corrosion potential of PCs to inform worker safety within the pharmaceutical space.

In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials.

Biphasic pro-melanogenic and pro-apoptotic effects of all-trans-retinoic acid (ATRA) on human melanocytes: time-course study.

Background: The effects of retinoids on melanogenesis and their mechanism as depigmenting agents in topical therapy have not been fully elucidated. Conflicting data about their impact on melanogenic pathways have been reported.

Objective: To investigate the effects of all-trans-retinoic acid (ATRA) on normal human melanocytes from Caucasian subjects.

Vaginal irritation models: the current status of available alternative and in vitro tests.

Mucosal surfaces, such as the vaginal epithelium, are natural barriers to infection that are constantly exposed to bacteria and viruses, and are therefore potential sites of entry for numerous pathogens. The vaginal epithelium can be damaged mechanically, e.g.

New insights on therapy with vitamin D analogs targeting the intracellular pathways that control repigmentation in human vitiligo.

Vitiligo is a progressive depigmenting disorder affecting 0.5-2% of the population worldwide in which destruction of functional melanocytes from epidermis is a composite of multiple processes influencing melanocyte function and survival. A number of studies have recently reported that the treatment with vitamin D compounds or their combination with ultraviolet light or corticosteroids enhances repigmentation in vitiligo; however, the causal relationship at the cellular and molecular levels has not so far been investigated.

Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease.

Tyrosinase is a key enzyme in the synthesis of melanin in skin and hair and has also been proposed to contribute to the formation of neuromelanin (NM). The presence of NM, which is biochemically similar to melanin in peripheral tissues, identifies groups of neurons susceptible in Parkinson's disease (PD). Whether tyrosinase is beneficial or detrimental to neurons is unclear; whilst the enzyme activity of tyrosinase generates dopamine-quinones and other oxidizing compounds, NM may form a sink for such radical species.