Synthesis and Behavior of 1,4- and 2,5-(C) Isotopomers of Phenylenediamine in Reconstructed Human Epidermis Using High Resolution Magic Angle Spinning NMR.

-Phenylenediamine (PPD) has been classified as a strong skin allergen, but when it comes to toxicological concerns, benzoquinone diamine (BQDI), the primary oxidation derivative of PPD, is frequently considered and was shown to covalently bind nucleophilic residues on model peptides. However, tests in solution are far from providing a reliable model, as the cutaneous metabolism of PPD is not covered. We now report the synthesis of two C substituted isotopomers of PPD, 1,4-(C)-phenylenediamine and 2,5-(C)-phenylenediamine , and the investigation of their reactivity in reconstructed human epidermis (RHE) using the high resolution magic angle spinning (HRMAS) NMR technique.

Autoxidized citronellol: Free radicals as potential sparkles to ignite the fragrance induced skin sensitizing pathway.

Citronellol, one of the most used fragrance compounds worldwide, is one ingredient of Fragrance Mix II used to assess skin allergy to fragrances in dermatitis patients. Pure citronellol is non-allergenic. Main issue is it autoxidizes when exposed to air becoming then allergenic.

Limonene and linalool hydroperoxides review: Pros and cons for routine patch testing.

Limonene and linalool are among the most common fragrance terpenes used in everyday products. They are pre-haptens, forming hydroperoxides (Lim-OOHs, Lin-OOHs) upon oxidation and inducing frequent positive patch test reactions in patients with dermatitis, and yet they are not routinely tested in Europe. This review evaluates current patch testing with Lim-OOHs and Lin-OOHs by asking whether hydroperoxide patch testing is warranted, examining the difficulties or challenges related to reading and interpreting hydroperoxide patch test results with currently available material, and assessing their relevance.

Electron paramagnetic resonance and spin trapping to detect free radicals from allergenic hydroperoxides in contact with the skin: From the molecule to the tissue.

A major research topic consists of revealing the contribution of radical-mediated reactions in dermatological diseases related to xenobiotic-induced stress to succeed risk-assessment procedures protecting producers and consumers. Allergic contact dermatitis is the clinically relevant consequence of skin sensitization, one of the most critical occupational and environmental health issues related to xenobiotics exposure. The first key event identified for the skin sensitization process to a chemical is its aptitude to react with epidermal proteins and form antigenic structures that will further trigger the immune response.

Bikini textile contact dermatitis: A Sherlockian approach revealing 2,4-dichlorophenol as a potential textile contact allergen.

Background: Different textile constituents may act as allergens and/or irritants and provoke textile contact dermatitis (TCD).

Objectives: To report a case of TCD caused by ethylene glycol monododecyl ether and 2,4-dichlorophenol, present in a bikini.

Methods: A woman presented with an eczematous, pruritic rash in the area of the bikini straps and back.

In Situ Alkylation of Reconstructed Human Epidermis by Methyl Methanesulfonate: A Quantitative HRMAS NMR Chemical Reactivity Mapping.

Allergic contact dermatitis (ACD) is a reaction of the immune system resulting from skin sensitization to an exogenous hazardous chemical and leading to the activation of antigen-specific T-lymphocytes. The adverse outcome pathway (AOP) for skin sensitization identified four key events (KEs) associated with the mechanisms of this pathology, the first one being the ability of skin chemical sensitizers to modify epidermal proteins to form antigenic structures that will further trigger the immune system. So far, these interactions have been studied in solution using model nucleophiles such as amino acids or peptides.

Mechanistic Insights on Skin Sensitization to Linalool Hydroperoxides: EPR Evidence on Radical Intermediates Formation in Reconstructed Human Epidermis and C NMR Reactivity Studies with Thiol Residues.

Linalool is one of the most commonly used fragrance terpenes in consumer products. While pure linalool is considered as non-allergenic because it has a very low skin sensitization potential, its autoxidation on air leads to allylic hydroperoxides that have been shown to be major skin sensitizers. These hydroperoxides have the potential to form antigens radical mechanisms.

Formation of methyl radicals derived from cumene hydroperoxide in reconstructed human epidermis: an EPR spin trapping confirmation by using C-substitution.

Dermal exposure to cumene hydroperoxide (CumOOH) during manufacturing processes is a toxicological issue for the industry. Its genotoxicity, mutagenic action, ability to promote skin tumour, capacity to induce epidermal hyperplasia, and aptitude to induce allergic and irritant skin contact dermatitis are well known. These toxic effects appear to be mediated through the activation to free radical species such as hydroxyl, alkoxyl, and alkyl radicals characterised basically by electron paramagnetic resonance (EPR) and spin-trapping (ST) techniques.

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.

Exposure source for skin sensitizing hydroperoxides of limonene and linalool remains elusive: An analytical market surveillance.

Positive patch test reactions of dermatological patients to oxidized samples of linalool and limonene are frequently reported. The sensitizing ingredients in the oxidation mixtures are hydroperoxides (HP). It is not clear whether fragranced consumer products are a relevant exposure source for HP.

Association Between Severe Acute Contact Dermatitis Due to Nigella sativa Oil and Epidermal Apoptosis.

Importance: Nigella sativa oil (NSO) is widely used for cosmetic and culinary purposes. Cases of severe acute contact dermatitis due to NSO are poorly described, with no histologic description.

Objectives: To describe the clinical and histologic features of severe acute contact dermatitis due to NSO and investigate the components responsible for such eruptions.

Isothiazolinones are still widely used in paints purchased in five European countries: a follow-up study.

Background: An increasing incidence of contact allergy to methylisothiazolinone (MI) has been seen, caused, in particular, by cosmetic products and paints. A study from 2015 showed that 93.0% of paints bought in five European countries contained MI.

Editor's Highlight: Fragrance Allergens Linalool and Limonene Allylic Hydroperoxides in Skin Allergy: Mechanisms of Action Focusing on Transcription Factor Nrf2.

Allergic contact dermatitis is regarded as the most frequent expression of immunotoxicity in humans. Many odorant terpenes commonly used in fragrance compositions are considered as weak skin sensitizers, whereas some of their autoxidation products, allylic hydroperoxides, are classified as strong sensitizers according to the local lymph node assay. However, the mechanism of their effects on the immune system remains unclear.

Self-testing for contact allergy to hair dyes - a 5-year follow-up multicentre study.

Background: In 2011, a multicentre study was conducted in order to determine how hair dye manufacturers instructed consumers to perform a self-test prior to dyeing their hair, in order to identify individuals who are likely to react upon subsequent hair dyeing. A number of concerns were raised concerning the variability in instructions between products and producers, and the safety and validity of this tool.

Objectives: To perform a 5-year follow-up study in order to determine whether manufacturers still recommend a self-test, and if so, whether the procedures have been changed.

Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens.

Allergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant.

In situ chemical behaviour of methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI) in reconstructed human epidermis: a new approach to the cross-reactivity issue.

Background: Methylisothiazolinone (MI) [with methylchloroisothiazolinone (MCI) in a ratio of 1:3, a well-recognized allergenic preservative] was released as an individual preservative in the 2000s for industrial products and in 2005 for cosmetics. The high level of exposure to MI since then has provoked an epidemic of contact allergy to MI, and an increase in MI/MCI allergy. There are questions concerning the MI/MCI cross-reaction pattern.

Methylisothiazolinone and benzisothiazolinone are widely used in paint: a multicentre study of paints from five European countries.

Background: In view of the current epidemic of contact allergy to methylisothiazolinone (MI), it is important to clarify the extent of use of MI and related isothiazolinones in paints currently available for the consumer and worker in Europe.

Objectives: To elucidate the use and concentrations of MI, methylchloroisothiazolinone (MCI) and benzisothiazolinone (BIT) in paints on the European retail market.

Methods: Wall paints (n = 71) were randomly purchased in retail outlets in five European countries.

An immune response study of oakmoss absolute and its constituents atranol and chloroatranol.

Background: Atranol and chloroatranol are the main allergens of oakmoss absolute. However, the immune responses induced by these substances are poorly characterized.

Objectives: To characterize immune responses induced by atranol, chloroatranol and oakmoss absolute in mice.

Reactivity of chemical sensitizers toward amino acids in cellulo plays a role in the activation of the Nrf2-ARE pathway in human monocyte dendritic cells and the THP-1 cell line.

Allergic contact dermatitis resulting from skin sensitization is an inflammatory skin disease linked to the use of chemicals termed haptens. Chemical reactivity is necessary for a chemical to be a sensitizer, allowing both covalent binding to proteins and maturation of dendritic cells (DCs) by mimicking "danger signals." The aim of this study was to evaluate how the reactivity of chemical sensitizers toward amino acids translates into a biological response using the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway, which was assessed by the induction of three Nrf2 target genes (ho-1, nqo1, and il-8) and Nrf2 protein accumulation.

In chemico evaluation of prohapten skin sensitizers: behavior of 2-methoxy-4-(¹³C)methylphenol in the peroxidase peptide reactivity assay (PPRA) as an alternative to animal testing.

In chemico methods, based on the assessment of a hapten's reactivity toward peptides, have been proposed as alternative methods for the assessment of the skin sensitizing potential of chemicals. However, even with these approaches showing promise, a major drawback is the activation of prohaptens, i.e.