Safety assessment for nail cosmetics: Framework for the estimation of systemic exposure through the nail plate.

All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety assessment. However, data on the exposure, especially via ungual route (nail plate) are limited.

Common fragrance chemicals activate dendritic cells in coculture with keratinocytes.

Background: Fragrances are important contact allergens; however, investigation of their skin sensitization potency has been challenging in new approach methods (NAMs). Many fragrance chemicals are susceptible to autoxidation or can be metabolized by enzymes constitutively expressed in skin keratinocytes. Strong sensitizers can be formed in both of these processes.

The 2-Methoxymethyl Modification of p -Phenylenediamine Reduces the Sensitization Risk for Hairdressers to Hair Dyes-An Occupational Hand Exposure-Based Risk Assessment.

Background: Allergic contact dermatitis involving the hands is a common occupational skin disease for hairdressers and the potent sensitizers p -phenylenediamine (PPD) and toluene-2,5-diamine (PTD) are associated with the development of occupational allergic contact dermatitis.

Objective: The aim of the study was to analyze whether the use of the moderate sensitizer 2-methoxymethyl-PPD (ME-PPD) in professional hair dyes is a suitable tool to reduce the occupational contact allergy risk for hairdressers.

Methods: Hand exposure of hairdressers (N = 11) to ME-PPD was analyzed under routine hair coloring conditions in commercial salons.

The HaCaT/THP-1 Cocultured Activation Test (COCAT) for skin sensitization: a study of intra-lab reproducibility and predictivity.

The Cocultured Activation Test (COCAT) consists of cocultured HaCaT (human keratinocyte cell line) and THP-1 cells (surrogate of antigen presenting cells). Individually, these cell lines are used to address key event 2 and 3 of the skin sensitization Adverse Outcome Pathway (AOP). Their exposure in coculture was found to have the potential to increase their response to sensitizing chemicals, enable the detection of pro-haptens and support the identification of skin sensitization potency.

Understanding the skin sensitization capacity of ascaridole: a combined study of chemical reactivity and activation of the innate immune system (dendritic cells) in the epidermal environment.

To improve the prediction of the possible allergenicity of chemicals in contact with the skin, investigations of upstream events are required to better understand the molecular mechanisms involved in the initiation of allergic reactions. Ascaridole, one of the compounds responsible for skin sensitization to aged tea tree oil, degrades into intermediates that evolve via different mechanisms involving radical species. We aimed at broadening the knowledge about the contribution of radical intermediates derived from ascaridole to the skin sensitization process by assessing the reactivity profile towards amino acids, identifying whether free radicals are formed in a reconstructed human epidermis (RHE) model and their biological properties to activate the immune system, namely dendritic cells in their natural context of human HaCaT keratinocytes and RHE.

Sensitization potential and potency of terpene hydroperoxides in the cocultured activation test method.

Background: Positive patch test reactions to mixtures of oxidized terpenes containing allergenic hydroperoxides are frequently reported. However, human sensitization data for these hydroperoxides are not available.

Objectives: To analyse and evaluate the human sensitization potential and potency of hydroperoxides in vitro by using human cells.

An in vitro coculture system for the detection of sensitization following aerosol exposure.

The aim of the study was to develop an in vitro model that mimics the alveolar-capillary barrier and that allows assessment of the respiratory sensitizing potential of respiratory sensitizers. The 3D in vitro model cultured at the air liquid interface consists of alveolar type II epithelial cells (A549), endothelial cells (EA.hy926), macrophage-like cells (PMA-differentiated THP-1) and dendritic-like cells (non-differentiated THP-1).

A coculture system composed of THP-1 cells and 3D reconstructed human epidermis to assess activation of dendritic cells by sensitizing chemicals after topical exposure.

A key event of the adverse outcome pathway for skin sensitization is the activation of dendritic cells (DC). To be most close to the in vivo situation, we combined for the first time reconstructed human epidermis (RHE) in coculture with THP-1 cells, as surrogate for DC. THP-1 cells were placed underneath RHE (SkinEthic™, OS-REp).

Allergy Alert Test for p-Phenylenediamine-Allergic Hair Dye Users.

Background: Contact dermatitis to hair dyes remains a health concern. Regulations in many countries require consumer self-testing for hair dyes, but no standardized procedure exists.

Objective: The aim of this study was to develop a self-test protocol for an allergy alert test (AAT) that can elicit a self-noticeable alert signal in p-phenylenediamine (PPD)-allergic consumers.

Cross-elicitation responses to 2-methoxymethyl-p-phenylenediamine in p-phenylenediamine-allergic individuals: Results from open use testing and diagnostic patch testing.

Background: Allergic contact dermatitis caused by p-phenylenediamine (PPD) is a health concern for hair dye users. Because of its lower sensitization potency, the PPD derivative 2-methoxymethyl-p-phenylenediamine (ME-PPD) has been developed as an alternative hair dye for primary prevention. However, cross-elicitation responses can occur in PPD-allergic subjects.

Skin sensitization quantitative risk assessment for occupational exposure of hairdressers to hair dye ingredients.

Occupational exposure of hairdressers to hair dyes has been associated with the development of allergic contact dermatitis (ACD) involving the hands. p-Phenylenediamine (PPD) and toluene-2,5-diamine (PTD) have been implicated as important occupational contact allergens. To conduct a quantitative risk assessment for the induction of contact sensitization to hair dyes in hairdressers, available data from hand rinsing studies following typical occupational exposure conditions to PPD, PTD and resorcinol were assessed.

Respiratory sensitization: toxicological point of view on the available assays.

Respiratory sensitization as a consequence of exposure to chemical products has increased over the last decades, leading to an increase of morbidity. The increased use of synthetic compounds resulted in an exponential growth of substances to which we are potentially exposed on a daily basis. Some of them are known to induce respiratory sensitization, meaning that they can trigger the development of allergies.

State-of-the-art and new options to assess T cell activation by skin sensitizers: Cosmetics Europe Workshop.

Significant progress has been made in the development and validation of non-animal test methods for skin sensitization assessment. At present, three of the four key events of the Adverse Outcome Pathway (AOP) are assessable by OECD-accepted in vitro methods. The fourth key event describes the immunological response in the draining lymph node where activated dendritic cells present major histocompatibility complex-bound chemically modified peptides to naive T cells, thereby priming the proliferation of antigen-specific T cells.

Recent progress in N-acetyltransferase research: 7th international workshop on N-acetyltransferases (NAT): workshop report.

The 7th International Workshop on N-Acetyltransferases (NAT), held from 18 to 20 June 2016, was hosted by Brunhilde Blömeke and her team at the Trier University (Germany). The workshop addressed important aspects and latest advancements in the fields of NAT enzymes, endogenous functions of NATs, NAT gene nomenclature, genetic polymorphisms, and their associations with diseases as well as their use in diagnosis. Representatives from the leading teams performing research on NATs presented their excellent work, discussed the latest results, and created new ideas in the field of N-acetyltransferase research.

Endothelial responses of the alveolar barrier in vitro in a dose-controlled exposure to diesel exhaust particulate matter.

Background: During the last 250 years, the level of exposure to combustion-derived particles raised dramatically in western countries, leading to increased particle loads in the ambient air. Among the environmental particles, diesel exhaust particulate matter (DEPM) plays a special role because of its omnipresence and reported effects on human health. During recent years, a possible link between air pollution and the progression of atherosclerosis is recognized.

Tolerance to a Hair Dye Product Containing 2-Methoxymethyl-P-Phenylenediamine in an Ethnically Diverse Population of P-Phenylenediamine-Allergic Individuals.

Background: Allergic contact dermatitis after exposure to p-phenylenediamine (PPD)-containing hair dye products is a common and important clinical problem. Because there is a high rate of cross-elicitation of allergic contact dermatitis to other important hair dye products (such as p-toluene diamine and other aminophenol hair dyes) in PPD-allergic patients, safer alternative dyes with excellent hair coloring options are needed.

Objective: This study aimed to study tolerance to Me-PPD in a PPD-allergic cohort.

Keratinocytes improve prediction of sensitization potential and potency of chemicals with THP-1 cells.

In vitro approaches to address key steps of chemical-induced skin sensitization have been developed, but there is uncertainty how keratinocytes, which play a crucial role not only regarding xenobiotic metabolism but also skin inflammation, impact on a chemical's potential and potency to activate dendritic cells. We investigated these aspects by coculturing THP-1 cells, as surrogate dendritic cells, with HaCaT keratinocytes. We tested our HaCaT/THP-1 model with a set of 14 sensitizers, containing 7 prohaptens, and 10 non-sensitizers.

The role of the antioxidant ascorbic acid in the elicitation of contact allergic reactions to p-phenylenediamine.

Background: An allergic contact reaction is accompanied by high oxidative stress in the skin. Pretreatment of the skin with antioxidative substances could reduce the elicitation reaction.

Objectives: To investigate, in a proof-of-principle study, whether pretreatment of the skin with the antioxidant ascorbic acid reduces the elicitation reaction to a p-phenylenediamine (PPD)-containing hair dye in sensitized subjects.

Real-time detection of p-phenylenediamine penetration into human skin by in vivo Raman spectroscopy.

Background: Penetration, autoxidation and N-acetylation of p-phenylenediamine (PPD) have been studied in vitro and ex vivo. However, a clear understanding of in vivo PPD penetration and the formation of PPD derivatives is lacking.

Objectives: To obtain insights into the in vivo penetration, clearance and formation of PPD derivatives in human skin.

Activation of the Endoperoxide Ascaridole Modulates Its Sensitizing Capacity.

The monoterpene ascaridole, a fairly stable endoperoxide found in essential oils such as tea tree oil can provoke allergic contact dermatitis which has been evidenced under patch test conditions. However, concomitantly we observed irritative skin reactions that demand further data underlining the sensitization potential of ascaridole. Here, we studied the effects of ascaridole on dendritic cell (DC) activation and protein reactivity, 2 key steps of chemical-induced skin sensitization.

N-acetylation of aromatic amines: implication for skin and immune cells.

Frequently, aromatic amine (AA) contact to the skin occurs via occupational or 'life style' exposure to hair dye intermediates and couplers, usually monocyclic p-phenylenediamines and meta-substituted aminophenols. The transport of AA from the outer surface to the systemic circulation predominantly follows the intracellular route. Skin tends to have relatively higher phase II compared to phase I xenobiotic metabolizing enzyme capacity, and levels are generally regarded as lower than those in liver.