Review of the safety of octocrylene used as an ultraviolet filter in cosmetics

Octocrylene or octocrilene is an organic ultraviolet (UV) filter which absorbs mainly UVB radiation and short UVA wavelengths. It is used in various cosmetic products to either provide an appropriate sun protection factor in sunscreen products or to protect cosmetic formulations from UV radiation. There is no discussion that UV filters are beneficial ingredients in cosmetics since they protect from skin cancer, but octocrylene has been recently incriminated to potentially induce adverse effects on the endocrine system in addition to having allergic and/or photoallergic potential. However, the substance has the advantage to work synergistically with other filters allowing a beneficial broad photoprotection, e.g. it stabilizes the UVA filter avobenzone (i.e. butylmethoxydibenzoylmethane). Like all chemicals used in cosmetics, the safety profile of octocrylene is constantly under assessment by the European Chemical Agency (ECHA) since it has been registered according to the European regulation Registration, Evaluation, Authorisation and Restriction of Chemicals. Summaries of safety data of octocrylene are publicly available on the ECHA website. This review aims to present the main safety data from the ECHA website, as well as those reported in scientific articles from peer-reviewed journals. The available data show that octocrylene does not have any endocrine disruption potential. It is a rare sensitizer, photocontact allergy is more frequent and it is considered consecutive to photosensitization to ketoprofen. Based on these results, octocrylene can be considered as safe when used as a UV filter in cosmetic products at a concentration up to 10%

Safety review of phenoxyethanol when used as a preservative in cosmetics

Phenoxyethanol, or 2-phenoxyethanol, has a large spectrum of antimicrobial activity and has been widely used as a preservative in cosmetic products for decades. It is effective against various Gram-negative and Gram-positive bacteria, as well as against yeasts, and has only a weak inhibitory effect on resident skin flora. According to the European Scientific Committee on Consumer Safety, phenoxyethanol is safe for all consumers \u2013 including children of all ages \u2013 when used as a preservative in cosmetic products at a maximum concentration of 1%. Adverse systemic effects have been observed in toxicological studies on animals but only when the levels of exposure were many magnitudes higher (around 200-fold higher) than those to which consumers are exposed when using phenoxyethanol-containing cosmetic products. Despite its widespread use in cosmetic products, phenoxyethanol is a rare sensitizer. It can be considered as one of the most well-tolerated preservatives used in cosmetic products

Interleukin-4 (IL-4) enhances and soluble interleukin-4 receptor (sIL-4R) inhibits histamine release from peripheral blood basophils and mast cells in vitro and in vivo

The aim of the study was to analyse the effect of interleukin-4 (IL-4) on allergen and anti-IgE mediated histamine release from basophils and human skin mast cells and to assess whether soluble recombinant interleukin-4 receptor (sIL4R) can inhibit these effects. Anti-IgE stimulated histamine release from peripheral blood basophils and mast cells of atopic donors was enhanced after preincubation with IL-4, whereas after preincubation with sIL-4R it was inhibited. These effects were even more pronounced when samples were stimulated with a clinically relevant allergen. In IL-4 preincubated skin mast cells, there was a similar enhancement of anti-IgE stimulated histamine release, which could again be inhibited by sIL-4R. The effects of IL-4 and sIL4R were dose- and time-dependent. Mice sensitized to ovalbumin and treated with soluble recombinant murine sIL-4R showed significantly reduced immediate-type cutaneous hypersensitivity responses compared with untreated mice. These in vivo effects were IgE independent, since there were no significant differences in total and allergen specific IgE/IgG1 antibody titres between treated and untreated mice. This indicates that IL4 exerts priming effects on histamine release by effector cells of the allergic response and that these effects are potently antagonized by soluble IL-4R both in vitro and in vivo

MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through β-Arrestin and Lack of Correlation with the FcεRI Pathway

Codeine stimulates skin mast cells and is therefore used in skin tests and as an inducer of experimental itch.MRGPRX2 responds to various drugs, including opioids, to elicit pseudoallergic reactions, but whether it represents the main opiate receptor of skin mast cells remains unknown. By combining a number of approaches, including the silencing of MRGPRX2, we now report that MRGPRX2 is indeed the dominant codeine receptor of dermal mast cells. Activation by codeine displayed profound subject variability and correlated with secretion elicited by compound 48/80 or substance P but not by FcεRI aggregation. Degranulation by codeine was attenuated by stem cell factor, whereas the opposite was found for FcεRI. Compound 48/80 or codeinealone was able to achieve maximum MRGPRX2 activation. MRGPRX2 was rapidly internalized on codeine binding in a b-arrestin-1‒dependent manner. Codeine-triggered b-arrestin activation was also established by the Tango assay. Prestimulation with MRGPRX2 agonists (but not C3a or FcεRI aggregation) resulted in refractoriness to further stimulation by the same or another MRGPRX2 ligand (cross desensitization). This was duplicated in a cell line (RBL-MRGPRX2). Collectively, codeine degranulates skin mast cells through MRGPRX2, at which it acts as a balanced ligand. It has yet to be determined whether codeine-induced refractoriness could be exploited to desensitize MRGPRX2 to prevent severe pseudoallergic reactions

Effects of allergen immunotherapy in the MASK-air study: a proof-of-concept analysis

info:eu-repo/semantics/publishedVersio

Cost Utility of Omalizumab Compared with Standard of Care for the Treatment of Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) negatively impacts patient quality of life and productivity and is associated with considerable indirect costs to society. OBJECTIVE: The aim of this study was to assess the cost utility of add-on omalizumab treatment compared with standard of care (SOC) in moderate or severe CSU patients with inadequate response to SOC, from the UK societal perspective. METHODS: A Markov model was developed, consisting of health states based on Urticaria Activity Score over 7 days (UAS7) and additional states for relapse, spontaneous remission and death. Model cycle length was 4 weeks, and total model time horizon was 20 years in the base case. The model considered early discontinuation of non-responders (response: UAS7 ≤6) and retreatment upon relapse (relapse: UAS7 ≥16) for responders. Clinical and cost inputs were derived from omalizumab trials and published sources, and cost utility was expressed as incremental cost-effectiveness ratios (ICERs). Scenario analyses included no early discontinuation of non-responders and an altered definition of response (UAS7 <16). RESULTS: With a deterministic ICER of £3183 in the base case, omalizumab was associated with increased costs and benefits relative to SOC. Probabilistic sensitivity analysis supported this result. Productivity inputs were key model drivers, and individual scenarios without early discontinuation of non-responders and adjusted response definitions had little impact on results. ICERs were generally robust to changes in key model parameters and inputs. CONCLUSIONS: In this, the first economic evaluation of omalizumab in CSU from a UK societal perspective, omalizumab consistently represented a treatment option with societal benefit for CSU in the UK across a range of scenarios

Influence heat-reflective coating on the decrease of heat losses of window constructions

Developed theoretical and methodological foundations of the optimal choice of space-planning and constructive decisions of low-rise buildings blocked type, aimed at improving efficiency of investment, energy and resource saving, creation of comfortable conditions for the population, ensure sustainable development of low-rise construction in the context of socio-economic priorities in the climatic zoning of the area of construction

The SCF/KIT axis in human mast cells: capicua acts as potent KIT repressor and ERK predominates PI3K

BACKGROUND: The SCF/KIT axis regulates nearly all aspects of mast cell (MC) biology. A comprehensive view of SCF-triggered phosphorylation dynamics is lacking. The relationship between signaling modules and SCF-supported functions likewise remains ill-defined. METHODS: MCs were isolated from human skin; upon stimulation by SCF, global phosphoproteomic changes were analyzed by LC-MS/MS and selectively validated by immunoblotting. MC survival was inspected by YoPro; BrdU incorporation served to monitor proliferation. Gene expression was quantified by RT-qPCR and cytokines by ELISA. Pharmacological inhibitors were supplemented by ERK1 and/or ERK2 knock-down. CIC translocation and degradation were studied in nuclear and cytoplasmic fractions. CIC's impact on KIT signaling and function was assessed following RNA interference. RESULTS: ≈5,400 out of ≈10,500 phosphosites experienced regulation by SCF. The MEK/ERK cascade was strongly induced surpassing STAT5>PI3K/Akt>p38>JNK. Comparison between MEK/ERK's and PI3K's support of basic programs (apoptosis, proliferation) revealed equipotency between modules. In functional outputs (gene expression, cytokines), ERK was the most influential kinase. OSM and LIF production was identified in skin MCs. Strikingly, SCF triggered massive phosphorylation of a protein not associated with KIT previously: CIC. Phosphorylation was followed by CIC's cytoplasmic appearance and degradation, the latter sensitive to protease- but not preoteasome-inhibition. Both shuttling and degradation were ERK-dependent. Conversely, CIC-siRNA facilitated KIT-signaling, functional outputs and survival. CONCLUSION: The SCF/KIT axis shows notable strength in MCs, and MEK/ERK as most prominent module. An inhibitory circuit exists between KIT and CIC. CIC stabilization in MCs may turn out as a therapeutic option to interfere with allergic and MC-driven diseases