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Pharmaceuticals and personal care products (PPCPs) exhibit varying biodegradability during the acidogenic and methanogenic phases of anaerobic digestion. However, there is limited information regarding the end products generated during these processes. This work investigates the biotransformation products (BTPs) generated in a two-phase (TP) acidogenic-methanogenic (Ac-Mt) bioreactor using advanced suspect and nontarget strategies. Fourteen BTPs were confidently identified from ten parent PPCPs including carbamazepine (CBZ), naproxen (NPX), diclofenac (DCF), ibuprofen (IBU), acetaminophen (ACT), metoprolol (MTP), sulfamethoxazole (SMX), ciprofloxacin (CIP), methylparaben (MPB) and propylparaben (PPB). These BTPs were linked with oxidation reactions such as hydroxylation, demethylation and epoxidation. Their generation was related to organic acid production, since all metabolites were detected during acidogenesis, with some being subsequently consumed during methanogenesis, e.g., aminothiophenol and kynurenic acid. Another group of BTPs showed increased concentrations under methanogenic conditions, e.g., hydroxy-diclofenac and epoxy-carbamazepine. The most PPCPs showed high removal efficiencies (> 90 %) - SMX, CIP, NPX, MTP, ACT, MPB, PPB, while DCF, CBZ and IBU demonstrated higher persistence - DCF (42 %); CBZ (40 %), IBU (47 %). The phase separation of anaerobic digestion provided a deeper understanding of the biotransformation pathways of PPCPs, in addition to enhancing the biodegradability of the most persistent compounds, i.e., DCF, CBZ and IBU., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Anaerobic digestion in two sequential phases, acidogenesis and methanogenesis, has been shown to be beneficial for enhancing the biomethane generation from wastewater. In this work, the application of glycerol (GOH) as a fermentation co-substrate during the wastewater treatment was evaluated on the biodegradation of different pharmaceuticals and personal care products (PPCPs). GOH co-digestion during acidogenesis led to a significant increase in the biodegradation of acetaminophen (from 78 to 89%), ciprofloxacin (from 25 to 46%), naproxen (from 73 to 86%), diclofenac (from 36 to 48%), ibuprofen (from 65 to 88%), metoprolol (from 45 to 59%), methylparaben (from 64 to 78%) and propylparaben (from 68 to 74%). The heterotrophic co-metabolism of PPCPs driven by glycerol was confirmed by the biodegradation kinetics, in which k bio (biodegradation kinetics constant) values increased from 0.18 to 2.11 to 0.27-3.60 L g -1 -VSS d -1 , for the operational phases without and with GOH, respectively. The assessment of metabolic pathways in each phase revealed that the prevalence of aromatic compounds degradation, metabolism of xenobiotics by cytochrome P 450 , and benzoate degradation routes during acidogenesis are key factors for the enzymatic mechanisms linked to the PPCPs co-metabolism. The phase separation of anaerobic digestion was effective in the PPCPs biodegradation, and the co-fermentation of glycerol provided an increase in the generation potential of biomethane in the system (energetic potential of 5.0 and 6.3 kJ g -1 -COD removed , without and with GOH, respectively). This study showed evidence that glycerol co-fermentation can exert a synergistic effect on the PPCPs removal during anaerobic digestion mediated by heterotrophic co-metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The wide application of benzophenones (BPs), such as benzophenone-3 (BP3), as an ingredient in sunscreens, cosmetics, coatings, and plastics, has led to their global contamination in aquatic environments. Using the marine diatom Chaetoceros neogracilis as a model, this study assessed the toxic effects and mechanisms of BP3 and its two major metabolites (BP8 and BP1). The results showed that BP3 exhibited higher toxicity on C. neogracilis than BP8 and BP1, with their 72-h median effective concentrations being 0.4, 0.8 and 4 mg/L, respectively. Photosynthesis efficiencies were significantly reduced after exposure to environmentally relevant concentrations of the three benzophenones, while cell viability, membrane integrity, membrane potential, and metabolic activities could be further impaired at their higher concentrations. Comparative transcriptomic analysis, followed by gene ontology and KEGG pathway enrichment analyses unraveled that all the three tested benzophenones disrupted photosynthesis and nitrogen metabolism of the diatom through alteration of similar pathways. The toxic effect of BP3 was also attributable to its unique inhibitory effects on eukaryotic ribosome biosynthesis and DNA replication. Taken together, our findings underscore that benzophenones may pose a significant threat to photosynthesis, oxygen production, primary productivity, carbon fixation, and the nitrogen cycle of diatom in coastal waters worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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. Based on the physicochemical properties of human nails and permeability data of topical onychomycosis drugs, the nail plate is considered a good barrier to chemicals. We examine factors impacting penetration of nail care ingredients through the nail plate, including properties of the nails of the ingredients and formulations. The molecular weight, vapor pressure, logP, water solubility, and keratin binding, as well as formulations properties e.g., polymerization of acrylate monomers are considered important factors affecting penetration. To estimate systemic exposure of nail care ingredients through the nail plate, a standardized framework is applied that quantifies the impacts of these properties on penetration with an adjustment factor for each of these influencing properties. All the adjustment factors are then consolidated to derive an integrated adjustment factor which can be used for calculation of the systemic exposure dose for the ingredient. Several case studies are presented to reflect how this framework can be used in the exposure assessment for nail cosmetic products., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Triclosan has been extensively used as a preservative in cosmetics and personal care products. However, its accumulation represents a real environmental threat. Thus, its phytotoxic impact needs more consideration. Our study was conducted to highlight the phytotoxic effect of triclosan on the growth, ROS homeostasis, and detoxification metabolism of two different plant species i.e., legumes (Glycine max) and grass (Avena sativa). Moreover, we investigated the potentiality of plant growth-promoting bacteria (ST-PGPB) in mitigating the phytotoxic effect of triclosan. Triclosan induced biomass (fresh and dry weights) reduction in both plants, but to a higher extent in oats. This decline was associated with a noticeable increment in the oxidative damage (e.g., MDA and H 2 O 2 ) and detoxification metabolites such as metallothionein (MTC), phytochelatins (PCs), and glutathione-S-transferase (GST). This elevation was associated with a remarkable reduction in both enzymatic and non-enzymatic antioxidants. On the other hand, the bioactive strain of ST-PGPB, Salinicoccus sp. JzA1 significantly alleviated the harmful effect of triclosan on both soybean and oat plants by enhancing their biomass, photosynthesis, as well as levels of minerals (K, Ca, P, Mn, and Zn). In parallel, a striking quenching in oxidative damage and an obvious improvement in non-enzymatic (polyphenols, tocopherols, flavonoids) and enzymatic antioxidants were observed. Furthermore, Salinicoccus sp. JzA1 augmented the detoxification metabolism by enhancing the levels of phytochelatins, metallothionein, and glutathione-S-transferase (GST) activity in a species-specific manner which is more apparent in soybean rather than in oat plants. To this end, stress mitigating impact of Salinicoccus sp. JzA1 provides a basis to improve the resilience of crop species under cosmetics and personal care products toxicity., Competing Interests: Declaration of competing interest All the authors disclosed that there is no any financial or personal relationship that may be perceived as influencing their work., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Previous research has emphasized the effects of lifestyle and genetics on ageing. However, the association between exposure to phthalates, which are extensively used in cosmetics and personal care products, and ageing is still unclear., Method: Data for 4711 subjects from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010 were incorporated in the present study. The acceleration of the Klemera-Doubal method-biological age (KDM-BA) and phenotypic Age (PhenoAge) were measured by the composite of 13 biomarkers. Multiple-linear and weighted-quantile sum (WQS) regression models were constructed to explore the relationships of single- and combined-phthalate exposures, as indicated by urinary phthalate metabolites, with KDM-BA and PhenoAge. A generalized additive model (GAM) was fitted to explore the potential nonlinear relationships among the above variables., Results: Except for mono-(carboxynonyl), all urinary phthalate metabolites were associated with biological ageing, with correlation coefficients ranging from 0.241 to 0.526; however, mono-ethyl presented a negative correlation. The WQS models revealed mixed effects of combined urinary phthalate metabolites on ageing, with a 0.22-year ((95 % CI) 0.09, 0.32) increase in KDM-BA acceleration and a 0.27-year ((95 % CI) 0.13, 0.37) increase in PhenoAge acceleration for each decile increase in urinary phthalate metabolites. Moreover, MCPP, MEOHP, and MBzP seemed to be the top three phthalates in terms of biological ageing, with weights of 33.3 % and 32.2 %, 29.2 % and 17.2 %, and 21.5 % and 30.1 % in KDM-BA and PhenoAge acceleration, respectively., Conclusion: Single-phthalate exposure was mostly associated with the ageing process, and combined-phthalate exposure presented mixed effects on biological ageing, emphasizing phthalate exposure as a significant risk factor for ageing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pharmaceuticals and personal care products (PPCPs) ubiquitously occur in the environment, resulting in detrimental effects on human health and other organisms. With the application of compost, manure and biosolids and the reclamation of treated wastewater, PPCP contaminants are introduced into the terrestrial and aquatic environments, giving rise to potential accumulation in plants. As PPCPs represent a range of chemicals with diversified physicochemical properties, their uptake and bioaccumulation in the plant show great differences, which have drawn increasing attention from both research communities and the general public in recent years. To date, there are few quantitative assessments of the potential of plants to take up and translocate PPCPs, and available data on metabolism of PPCPs are also limited. Therefore, by assembling the literature, this review summarizes the uptake and accumulation pattern of PPCPs within plants, and explicitly clarifies the plant uptake and translocation processes from the perspective of the root and foliar uptake, short-distance and long-distance transport. The main factors influencing the uptake and transfer of PPCPs are also shed light on in this review. These factors include chemical hydrophobicity, ionization properties, pH, molecular size, lipid and carbohydrate content, transpiration rates, etc. Furthermore, related enzymes, transformation products and the role of plant-bacteria partnership in the metabolic process are elucidated. Moreover, the plant development, physiological and biochemical responses to the exposure to the PPCPs are summarized. Finally, on the basis of the results presented, research gap areas and questions have been also identified with future perspectives. Overall, this paper presents information for a more comprehensive understanding of the uptake, accumulation, translocation and metabolism of PPCPs in plants, and could be a valuable guideline to the key physiological and biochemical process of PPCPs from entering the plant and their phytotoxicity when assessing the risk of PPCPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dermal drug delivery has emerged as a promising alternative to traditional methods of drug administration due to its non-invasive nature and ease of use. However, the stratum corneum, the outermost layer of the skin, presents a significant barrier to drug penetration. Niosomes, self-assembled vesicular structures composed of nonionic surfactants and cholesterol, have been extensively investigated as a means of overcoming this barrier and improving the efficacy of dermal drug delivery. This review summarizes the current state of research on the use of niosomes in dermal drug delivery in cosmetics, with a particular focus on their formulation, characterization, and application in the delivery of various drug classes. The review highlights the advantages of niosomes over conventional drug delivery methods, including improved solubility and stability of drugs, controlled release, and enhanced skin permeation. The review also discusses the challenges associated with niosome-based drug delivery, such as their complex formulation and optimization, and the need for further studies on their long-term safety and toxicity.

Topical administration of active substances may be promoted by optimizing not only the vehicle formulation but also the application protocol. The formulation aspects are widely studied in the literature while a few works are dedicated to the development of application methods. In this context, we studied an application protocol usable as a part of skincare routine by investigating the effect of massage on the skin penetration of retinol. Retinol is a lipophilic molecule widely used as an anti-ageing firming agent in cosmetic formulations. Massage was applied to pig skin explants mounted to Franz diffusion cells after or before the deposit of the retinol-loaded formulation. Thetype of skin massage (roll or rotary type) and its duration were varied.The massage protocol had a significant influence on retinol skin penetration. Due to its highly lipophilic character, retinol accumulated into the stratum corneum but, depending on the massage protocol, a significant retinol concentration was obtained after 4 h in epidermis and dermis layers. Results showed that the roll-type massage was significantly more efficient than the rotary process that exhibited little effect on retinol cutaneous penetration. Such results could be interesting for the development of massage devices in association with cosmetic formulations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Demand on natural products that contain biological ingredients mimicking growth factors and cytokines made natural polysaccharides popular in pharmaceutical and cosmetic industries. Levan is the β-(2-6) linked, nontoxic, biocompatible, water-soluble, film former fructan polymer that has diverse applications in pharmacy and cosmeceutical industries with its moisturizing, whitening, anti-irritant, anti-aging and slimming activities. Driven by the limited reports on few structurally similar levan polymers, this study presents the first systematic investigation on the effects of structurally different extremophilic Halomonas levan polysaccharides on human skin epidermis cells. In-vitro experiments with microbially produced linear Halomonas levan (HL), its hydrolyzed, (hHL) and sulfonated (ShHL) derivatives as well as enzymatically produced branched levan (EL) revealed increased keratinocyte and fibroblast proliferation (113-118 %), improved skin barrier function through induced expressions of involucrin (2.0 and 6.43 fold changes for HL and EL) and filaggrin (1.74 and 3.89 fold changes for hHL and ShHL) genes and increased type I collagen (2.63 for ShHL) and hyaluronan synthase 3 (1.41 for HL) gene expressions together with fast wound healing ability within 24 h (100 %, HL) on 2D wound models clearly showed that HL and its derivatives have high potential to be used as natural active ingredients in cosmeceutical and skin regenerating formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are phospholipidic bi-layer enclosed nanoparticles secreted naturally by all cell types. They are attracting increasing attention in the fields of nanomedicine, nutraceutics and cosmetics as biocompatible carriers for drug delivery, with intrinsic properties beneficial to human health. Scientific work now focuses on developing techniques for isolating EVs that can translate into industrial-scale production and meet rigorous clinical requirements. The science of EVs is ongoing, and many pitfalls must be addressed, such as the requirement for standard, reproducible, inexpensive, and Good Manufacturing Practices (GMP) adherent EV processing techniques. Researchers are exploring the use of alternative sources to EVs derived from mammalian cultures, such as plant EVs, as well as the use of bacteria, algae and milk. Regarding the downstream processing of EVs, many alternative techniques to the ultracentrifugation (UC) protocols most commonly used in the laboratory are emerging. In the context of process scale-up, membrane-based processes for isolation and purification of EVs are the most promising, either as stand-alone processes or in combination with chromatographic techniques. This review discusses current trends on EVs source selection and EVs downstream processing techniques, with a focus on plant-derived EVs and membrane-based techniques for EVs enrichment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nanotechnology suggests different innovative solutions to augment the worth of cosmetic products through the targeted delivery of content that manifests scientific innovation in research and development. Different nanosystems, like liposomes, niosomes, microemulsions, solid lipid nanoparticles, nanoform lipid carriers, nanoemulsions, and nanospheres, are employed in cosmetics. These nanosystems exhibit various innovative cosmetic functions, including site-specific targeting, controlled content release, more stability, improved skin penetration and enhanced entrapment efficiency of loaded compounds. Thus, cosmeceuticals are assumed as the highest-progressing fragment of the personal care industries that have progressed drastically over the years. In recent decades, cosmetic science has widened the origin of its application in different fields. Nanosystems in cosmetics are beneficial in treating different conditions like hyperpigmentation, wrinkles, dandruff, photoaging and hair damage. This review highlights the different nanosystems used in cosmetics for the targeted delivery of loaded content and commercially available formulations. Moreover, this review article has delineated different patented nanocosmetic formulation nanosystems and future aspects of nanocarriers in cosmetics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To measure progress and evaluate performance of the newest UB/UC/P&G skin penetration model we simulated an 18-compound subset of finite dose in vitro human skin permeation data taken from a solvent-deposition study of cosmetic-relevant compounds (Hewitt et al., J. Appl. Toxicol. 2019, 1-13). The recent model extension involved slowly reversible binding of solutes to stratum corneum keratins. The selected subset was compounds that are liquid at skin temperature. This set was chosen to distinguish between slow binding and slow dissolution effects that impact solid phase compounds. To adequately simulate the physical experiments there was a need to adjust the evaporation mass transfer coefficient to better represent the diffusion cell system employed in the study. After this adjustment the model successfully predicted both dermal delivery and skin surface distribution of 12 of the 18 compounds. Exceptions involved compounds that were cysteine-reactive, highly water-soluble or highly ionized in the dose solution. Slow binding to keratin, as presently parameterized, was shown to significantly modify the stratum corneum kinetics and diffusion lag times, but not the ultimate disposition, of the more lipophilic compounds in the dataset. Recommendations for further improvement of both modeling methods and experimental design are offered., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The cosmetic industry is dynamic and ever-evolving. Especially with the introduction and incorporation of nanotechnology-based approaches into cosmetics for evincing novel formulations that confers aesthetic as well as therapeutic benefits. Nanocosmetics acts via numerous delivery mechanisms which involves lipid nanocarrier systems, polymeric or metallic nanoparticles, nanocapsules, dendrimers, nanosponges,etc. Each of these, have particular characteristic properties, which facilitates increased drug loading, enhanced absorption, better cosmetic efficacy, and many more. This article discusses the different classes of nanotechnology-based cosmetics and the nanomaterials used for their formulation, followed by outlining the categories of nanocosmetics and the scope of their utility pertaining to skin, hair, nail, lip, and/or dental care and protection thereof. This review also highlights and discusses about the key drivers of the cosmetic industry and the impending need of corroborating a healthy regulatory framework, refocusing attention towards consumer needs and trends, inculcating sustainable techniques and tenets of green ecological principles, and lastly making strides in nano-technological advancements which will further propel the growth of the cosmetic industry., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Microalgae are complex photosynthetic organisms found in marine and freshwater environments that produce valuable metabolites. Microalgae-derived metabolites have gained remarkable attention in different industrial biotechnological processes and pharmaceutical and cosmetic industries due to their multiple properties, including antioxidant, anti-aging, anti-cancer, phycoimmunomodulatory, anti-inflammatory, and antimicrobial activities. These properties are recognized as promising components for state-of-the-art cosmetics and cosmeceutical formulations. Efforts are being made to develop natural, non-toxic, and environmentally friendly products that replace synthetic products. This review summarizes some potential cosmeceutical applications of microalgae-derived biomolecules, their mechanisms of action, and extraction methods.

Objective: The cosmetic industry endeavours to strengthen the greener and safer claims of processes to respond to the high demand from customers for natural and environmentally friendly products. High-frequency ultrasonication technology (HFUT) is a physical process enabling the stabilization of emulsions without requiring additional ingredients, such as emulsifying surfactants (ES) to be introduced into the formulations. In this study, key formulation characteristics of an emulsion synthesized by HFUT and a reference emulsion (RE) were compared, as well as the permeation kinetics of caffeine, used as a model active cosmetic ingredient, from both types of emulsions., Methods: The pH, droplet size and viscosity of emulsions prepared by the HFUT and the RE were determined and compared. The permeation of caffeine from the HFUT emulsion and the RE applied to the surface of reconstructed human epidermis (RHE) models was compared., Results: The ES-free formulations prepared by HFUT displayed a nearly 2-fold lower average droplet size and over 3-fold greater viscosity, compared to the RE. Despite these differences, the absence of ES in the HFUT emulsion did not significantly alter the permeation kinetics of caffeine through RHE. The caffeine steady-state flux, lag time and permeability coefficients differed by 20%-30% only., Conclusion: This study demonstrates the potential of the HFUT to yield topical cosmetic products with lower requirements ingredients-wise, without losing efficacy, supporting the possible implementation of the technology in the cosmetic industry., (© 2022 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Objective: The human epidermis is formed by the proliferation and differentiation of keratinocytes adjacent to the basement membrane. The outermost layer, the stratum corneum, is equipped with a barrier function that prevents water evaporation, and intercellular lipids play an important role in this barrier function. When the barrier is functioning normally, evaporation is prevented; however, when barrier function is impaired, moisture evaporates, resulting in dry and rough skin. Therefore, maintenance of normal barrier function is critical for maintaining normal skin function. Peroxisome proliferator-activated receptor α (PPARα) is mainly not only involved in lipid metabolism in the liver but is also expressed in the epidermis and is involved in inducing keratinocyte differentiation, promoting lipid production, maintaining barrier function and suppressing skin inflammation. Hence, compounds that activate PPARα are expected to control skin function. Therefore, we identified PPARα activators from among extracts of natural resources that have been approved for use in humans and analysed the effects of these extracts on skin function., Methods: First, extracts of 474 natural resources were screened using a PPARα activator screening cell line independently constructed in our laboratory. Next, reporter assays were performed using the Gal4-chimera system to evaluate whether these extracts act as ligands for PPARα. We then analysed their effect on primary normal human epidermal keratinocyte cells by using real-time RT-PCR. Finally, we evaluated PPARα activation effect by the combination of these extracts., Results: We identified 36 extracts having the effect of activating PPARα. In particular, #419, a Typha angustifolia spike extract, showed concentration-dependent transcriptional activation through PPARα-LBD and was considered to be likely to contain a compound that is a ligand of PPARα. #419 increased the expression of PPARα target genes and genes related to skin function in primary cultured human epidermal keratinocytes. Finally, the use of #419 in combination with nine extracts increased PPAR activity more than twice as much as #419 alone treatment., Conclusions: These results showed that the reporter cell line could be useful for discovering extracts of natural resources and that the identified Typha angustifolia spike extract could be used in cosmetics that activate PPARα, which expected to improve skin function., (© 2022 The Authors. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Propylidene phthalide (PP) is a cosmetic ingredient used in the fragrance industry and regulated for the limited content of 0.01% in cosmetic products in Korea. The aim of this study was to determine PP dermal absorption rate according to the Korea Ministry of Food and Drug Safety (MFDS) guidelines using in vitro Franz diffusion system. An analytical method in assessing PP was developed through method validation using LC-MS/MS. Linearity, precision, and accuracy were acceptable based upon MFDS guidelines. The stability of PP in receptor fluid (50% ethanol) at 32°C was sufficient up to 24 hr. Cream formulation (o/w) was topically applied to excised rat skin at a dose of 113 mg/cm 2 containing 0.7% PP. The time points for receptor fluid collection were set at 0, 1, 2, 4, 8, 12, and 24 hr. After 24 hr, the remaining formulation on the skin and stratum corneum (SC) were collected through swabbing with an alcohol cotton and tape stripping, respectively. The collected samples (swabbed-remained formulation, SC, and skin) were extracted using acetonitrile for 24 hr. Total dermal absorption rate of PP was approximately 24% in cream formulation. These findings may be used for further exposure evaluation of PP in human consumers.

Kombucha is a beverage made by fermenting sugared tea using a symbiotic culture of bacteria belonging to the genus Acetobacter, Gluconobacter, and the yeasts of the genus Saccharomyces along with glucuronic acid, which has health-promoting properties. The paper presents the evaluation of ferments as a potential cosmetic raw material obtained from Yerba Mate after different fermentation times with the addition of Kombucha. Fermented and unfermented extracts were compared in terms of chemical composition and biological activity. The antioxidant potential of obtained ferments was analyzed by evaluating the scavenging of external and intracellular free radicals. Cytotoxicity was determined on keratinocyte and fibroblast cell lines, resulting in significant increase in cell viability for the ferments. The ferments, especially after 14 and 21 days of fermentation showed strong ability to inhibit (about 40% for F21) the activity of lipoxygenase, collagenase and elastase enzymes and long-lasting hydration after their application on the skin. Moreover, active chemical compounds, including phenolic acids, xanthines and flavonoids were identified by HPLC/ESI-MS. The results showed that both the analyzed Yerba Mate extract and the ferments obtained with Kombucha may be valuable ingredients in cosmetic products., (© 2021. The Author(s).)

Skin appearance is essential for self-esteem and quality of life; consequently, skin care products represent a huge market. In particular, cosmeceuticals constitute a hybrid category of skin care formulations, at the interphase of cosmetics and pharmaceuticals, rationally designed to target (patho) physiological mechanisms aiming to enhance skin health and appearance. Cosmeceuticals are marketed as anti-ageing, anti-wrinkle, hair regrowth, skin whitening and wound healing agents with special emphasis on scar-free healing. An overview on recent cutting-edge advances concerning the discovery and development of enhanced performance cosmeceuticals by drug repositioning approaches is presented here. In this context, we propose "target repositioning," a new term, to highlight that druggable protein targets implicated in multiple diseases (hubs in the diseasome) can be exploited to accelerate the discovery of molecularly targeted cosmeceuticals that can promote skin health as an added benefit, which is a novel concept not described before. In this direction, emphasis is placed on the role of mouse models, for often untreatable skin diseases, as well as recent breakthroughs on monogenic rare skin syndromes, in promoting compound repositioning to innovative cosmeceuticals., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Naturally occurring peptides found in the human skin can serve particular biological activities and play roles as signaling molecules of various physiological processes such as homeostasis, growth, defense or immunity. Their great biological activity resulted in a growing interest in the pharmaceutical industry. Researchers consider peptides either promising compounds with potential application for human diagnosis, therapy or cosmetics. Peptides are becoming interesting cosmetic ingredients with the functions to reduce premature skin aging, improve the barrier function of skin, moisturize the skin, protect it from UV damage, and anti-inflammatory properties that alleviate acne and irritation. Till now, peptides of different origins were investigated in formulation developed to enhance collagen or elastin production, increase fibroblast proliferation, improve wound healing or skin condition. Most of them are obtained by chemical synthesis or by partial digestion of animal proteins. Short and easily synthesized peptides with alternative amino acid sequence, and combinations have created a new field of molecules inspired by nature and implemented in the cosmetic industry. Nowadays, peptides are cheaper and easier to produce in large quantities. The efficient process development methods allow obtaining nearly unlimited sequences, which makes them functionally preferred. Generally, cosmetic peptides are categorized as carrier peptides, neurotransmitter- affecting peptides, enzyme inhibitor peptides and signal peptides. The use of signal peptides in cosmetics increased over a few years. These molecules trigger a signaling cascade and stimulate fibroblast collagen production, the proliferation of elastin, fibronectin, laminin, etc. Thus, a literature search on a topical application of the most common signal peptides; and their current status in the cosmetic industry was carried out., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background & Objective: Nanoparticles are used in cosmetic and dermatologic products, due to better skin penetration properties. Incorporation of natural products exhibiting medicinal properties in nano-preparations could significantly improve the efficacy of these products and improve the quality of life without the side effects of synthetic formulations., Methods: We here report the green synthesis of Copper Oxide nanoparticles, using Cucumber extract, and their detailed bio-physical and bio-chemical characterization., Results: These Copper Oxide-Cucumber nanoparticles exhibit significant anti-bacterial and anti-fungal properties, Ultra Violet-radiation protection ability and reactive-oxygen species inhibition properties. Importantly, these nanoparticles do not exhibit significant cellular toxicity and, when incorporated in skin cream, exhibit skin rejuvenating properties., Conclusion: Our findings have implications for nanoparticle-based cosmetics and dermatologic applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A standard protocol was used to determine partition (K) and diffusion (D) coefficients in dermatomed human skin and isolated human skin layers for 50 compounds relevant to cosmetics ingredients. K values were measured in dermatomed skin, isolated dermis, whole epidermis, intact stratum corneum (SC), delipidized SC and SC lipids by direct measurements of the radioactivity in the tissue layers/lipid component vs. buffer samples. D determinations were made in dermatomed skin, isolated dermis, whole epidermis and intact SC using a non-linear regression of the cumulative receptor fluid content of radiolabeled compound, fit to the solution of Fick's 2nd Law. Correlation analysis was completed between K, D, and physicochemical properties. The amount of interindividual (donor) and intraindividual (replicate) variability in the K and D data was characterized for each skin layer and chemical. These data can be further used to help inform the factors that influence skin bioavailability and to help improve in silico models of dermal penetration., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exposure to multiple classes of contaminants, both legacy and contaminants of emerging concern (CECs), were assessed in tree swallow (Tachycineta bicolor) tissue and diet samples from 6 sites along the Maumee River, Ohio, USA, to understand both exposure and possible effects of exposure to those CECs for which there are little avian data. The 6 sites represented a gradient from intensive agriculture upstream to highly urbanized and industrial landscapes downstream; 1 or 2 remote Wisconsin lakes were assessed for comparative purposes. Cytochrome P450 induction, DNA damage, and thyroid function were also assessed relative to contaminant exposure. Bioaccumulative CECs, such as polybrominated diphenyl ethers (PBDEs) and perfluorinated substances, did not follow any upstream to downstream gradient; but both had significantly greater concentrations along the Maumee River than at the remote lake sites. Greater exposure to PBDEs was apparent in swallows at or near wastewater-treatment facilities than at other sites. Total polychlorinated biphenyl and total polycyclic aromatic hydrocarbon concentrations were greater in swallows at downstream locations compared to upstream sites and were associated with higher ethoxyresorufin-O-dealkylase activity. Few herbicides or nonorganochlorine insecticides were detected in swallow tissues or their food, except for atrazine and its metabolite desethylatrazine. Few pharmaceuticals and personal care products were detected except for DEET and iopamidol. Both were detected in most liver samples but not in eggs, as well as detected at the remote lake sites. This is one of the most comprehensive assessments to date of exposure and effects of a wide variety of CECs in birds. Environ Toxicol Chem 2020;39:1936-1952. © 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA., (© 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Parabens are widely used as preservatives in personal care products, foodstuffs, and pharmaceuticals. Concerns have been raised regarding the potential endocrine disruption effects of parabens. In the present study, the urinary concentration of four common parabens, including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP), in 100 Iranian adolescents randomly referring to health services centres were analyzed using GC/MS. The association of sociodemographic and lifestyle variables, collected through questionnaire, with the concentration of parabens also were studied. Median concentrations of MP, EP, PP, and BP were 92.21, 8.46, 12.26, and 8.42 µg/g creatinine, respectively. There was a strong positive significant correlation between MP and PP (r = 0.694) and moderate to a weak correlation between the other parabens. The concentration of urinary MP in females was significantly higher than those in male (p = 0.021). There was a significant negative association between different BMI groups and MP and EP. There also was a positive significant association between the MP and age, and between MP, EP, and PP, and tobacco use. Although the estimated daily intake of the parabens was lower than the Acceptable Daily Intake, it was higher than those reported in other countries. This confirms the widespread exposure of Iranian adolescents to the paraben compounds and their association with sociodemographic factors. This was the first study reporting the urinary parabens level in Iranian adolescents, and the data can be used as a basis for assessing the risk of exposure to parabens in the Iranian population in future studies.

A valuable approach to chemical safety assessment is the use of read-across chemicals to provide safety data to support the assessment of structurally similar chemicals. An inventory of over 6000 discrete organic chemicals used as fragrance materials in consumer products has been clustered into chemical class-based groups for efficient search of read-across sources. We developed a robust, tiered system for chemical classification based on (1) organic functional group, (2) structural similarity and reactivity features of the hydrocarbon skeletons, (3) predicted or experimentally verified Phase I and Phase II metabolism, and (4) expert pruning to consider these variables in the context of specific toxicity end points. The systematic combination of these data yielded clusters, which may be visualized as a top-down hierarchical clustering tree. In this tree, chemical classes are formed at the highest level according to organic functional groups. Each subsequent subcluster stemming from classes in this hierarchy of the cluster is a chemical cluster defined by common organic functional groups and close similarity in the hydrocarbon skeleton. By examining the available experimental data for a toxicological endpoint within each cluster, users can better identify potential read-across chemicals to support safety assessments.

Little information is available on the bioaccumulation and trophic transfer of pharmaceuticals and personal care products (PPCPs) in urban rivers system, particularly for those affected by water transfer. Herein, a comprehensive study was conducted to investigate the biological residues, bioaccumulation and trophic transfer of 45 PPCPs in the Nanjing Qinhuai River system under the background of water diversion projects. A total of 30 compounds were detected with a descending order of overall concentration as plankton > benthic mollusc > fish (except grass carp). Higher biological residues were observed in the downstream than those in the upstream, with the largest increase for fish (136.4 %) and the lowest increase for phytoplankton (5.4 %). However, the bioaccumulation classifications of most PPCPs were unchanged among the three different water-diversion regions. Trophic magnification factors (TMFs) of organic UV filters (homosalate, oxybenzone, ethylhexyl methoxycinnamate and octocrylene) ranged from 1.23 to 2.04, suggesting trophic magnification potential, while trophic dilution for pharmaceuticals (sertraline, citalopram, caffeine and roxithromycin) with TMFs of 0.42 to 0.50 were observed. A notable positive correlation was observed between the pH-dependent distribution coefficient (logDow) and the TMFs of the PPCPs (P < 0.05). Although the human health hazard assessment indicated no immediate health risk via the consumption of freshwater food, attention should be paid to the joint effects of PPCPs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Finite dose experiments represent clinical use wherein depletion of dose, evaporation of excipients, and gradual change in vehicle composition may occur. In the present study, we attempted a mathematical approach for predicting skin permeation and concentration of a cosmetic active, rhododendrol (RD), from complex vehicle-based formulations applied in finite dose. In vitro skin permeation and concentration studies of RD were conducted from formulations containing water and polyols with concentrations ranging from 10 to 100% under infinite and finite dose conditions using vertical Franz diffusion cells. Observed data for skin permeation and the viable epidermis and dermis (VED) concentration of RD were estimated by the differential equations under Fick's second law of diffusion together with water evaporation kinetics and changes in the partition coefficient from vehicles to the stratum corneum. As a result, a goodness-of-fit was observed allowing accurate estimation of skin permeation and VED concentration of RD. This mathematical approach could become a useful tool to estimate the skin permeation and concentration of actives from topical formulation applied in finite dose conditions likened in actual use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The abundance of xenobiotic metabolizing enzymes (XMEs) is different in the skin and liver; therefore, it is important to differentiate between liver and skin metabolism when applying the information to safety assessment of topically applied ingredients in cosmetics. Here, we have employed EpiSkin™ S9 and human liver S9 to investigate the organ-specific metabolic stability of 47 cosmetic-relevant chemicals. The rank order of the metabolic rate of six chemicals in primary human hepatocytes and liver S9 matched relatively well. XME pathways in liver S9 were also present in EpiSkin S9; however, the rate of metabolism tended to be lower in the latter. It was possible to rank chemicals into low-, medium- and high-clearance chemicals and compare rates of metabolism across chemicals with similar structures. The determination of the half-life for 21 chemicals was affected by one or more factors such as spontaneous reaction with cofactors or non-specific binding, but these technical issues could be accounted for in most cases. There were seven chemicals that were metabolized by liver S9 but not by EpiSkin S9: 4-amino-3-nitrophenol, resorcinol, cinnamyl alcohol and 2-acetylaminofluorene (slowly metabolized); and cyclophosphamide, benzophenone, and 6-methylcoumarin. These data support the use of human liver and EpiSkin S9 as screening assays to indicate the liver and skin metabolic stability of a chemical and to allow for comparisons across structurally similar chemicals. Moreover, these data can be used to estimate the systemic bioavailability and clearance of chemicals applied topically, which will ultimately help with the safety assessment of cosmetics ingredients., (© 2020 John Wiley & Sons, Ltd.)

OECD test guideline 428 compliant protocol using human skin was used to test the penetration of 56 cosmetic-relevant chemicals. The penetration of finite doses (10 μL/cm 2 ) of chemicals was measured over 24 hours. The dermal delivery (DD) (amount in the epidermis, dermis and receptor fluid [RF]) ranged between 0.03 ± 0.02 and 72.61 ± 8.89 μg/cm 2 . The DD of seven chemicals was comparable with in vivo values. The DD was mainly accounted for by the amount in the RF, although there were some exceptions, particularly of low DD chemicals. While there was some variability due to cell outliers and donor variation, the overall reproducibility was very good. As six chemicals had to be applied in 100% ethanol due to low aqueous solubility, we compared the penetration of four chemicals with similar physicochemical properties applied in ethanol and phosphate-buffered saline. Of these, the DD of hydrocortisone was the same in both solvents, while the DD of propylparaben, geraniol and benzophenone was lower in ethanol. Some chemicals displayed an infinite dose kinetic profile; whereas, the cumulative absorption of others into the RF reflected the finite dosing profile, possibly due to chemical volatility, total absorption, chemical precipitation through vehicle evaporation or protein binding (or a combination of these). These investigations provide a substantial and consistent set of skin penetration data that can help improve the understanding of skin penetration, as well as improve the prediction capacity of in silico skin penetration models., (© 2019 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

An understanding of the bioavailability of topically applied cosmetics ingredients is key to predicting their local skin and systemic toxicity and making a safety assessment. We investigated whether short-term incubations with S9 from the reconstructed epidermal skin model, EpiSkin™, would give an indication of the rate of chemical metabolism and produce similar metabolites to those formed in incubations with human skin explants. Both have advantages: EpiSkin™ S9 is a higher-throughput assay, while the human skin explant model represents a longer incubation duration (24 hours) model integrating cutaneous distribution with metabolite formation. Here, we compared the metabolism of 10 chemicals (caffeine, vanillin, cinnamyl alcohol, propylparaben, 4-amino-3-nitrophenol, resorcinol, 4-chloroaniline, 2-amino-3-methyl-3H-imidazo[4,5-F]quinoline and 2-acetyl aminofluorene) in both models. Both models were shown to have functional Phase 1 and 2 enzymes, including cytochrome P450 activities. There was a good concordance between the models with respect to the level of metabolism (stable vs. slowly vs. extensively metabolized chemicals) and major early metabolites produced for eight chemicals. Discordant results for two chemicals were attributed to a lack of the appropriate cofactor (NADP + ) in S9 incubations (cinnamyl alcohol) and protein binding influencing chemical uptake in skin explants (4-chloroaniline). These data support the use of EpiSkin™ S9 as a screening assay to provide an initial indication of the metabolic stability of a chemical applied topically. If required, chemicals that are not metabolized by EpiSkin™ S9 can be tested in longer-term incubations with in vitro human explant skin to determine whether it is slowly metabolized or not metabolized at all., (© 2019 John Wiley & Sons, Ltd.)

Cosmetics are a source of lifetime exposure to various substances including parabens, being the most popular synthetic preservatives. Because the use of cosmetics shows an increasing trend and some adverse health outcomes of parabens present in these products have been reported, the present review focused on the safety of dermal application of these compounds. Special attention has been paid to the absorption of parabens and their retention in the human body in the intact form, as well as to their toxicological characteristics. Particular emphasis has been placed on the estrogenic potential of parabens. Based on the available published data of the concentrations of parabens in various kinds of cosmetics, the average ranges of systemic exposure dose (SED) for methylparaben, ethylparaben, propylparaben, and butylparaben have been calculated. Safety evaluations [margin of safety (MoS)] for these compounds, based on their aggregate exposure, have also been performed. Moreover, evidence for the negative impact of methylparaben on skin cells has been provided, and the main factors that may intensify dermal absorption of parabens and their impact on the skin have been described. Summarizing, the use of single cosmetics containing parabens should not pose a hazard for human health; however, using excessive quantities of cosmetic preparations containing these compounds may lead to the development of unfavorable health outcomes. Due to the real risk of estrogenic effects, as a result of exposure to parabens in cosmetics, simultaneous use of many cosmetic products containing these preservatives should be avoided., (© 2020 John Wiley & Sons, Ltd.)

Although, several recent greenhouse studies are beginning to address the uptake of pharmaceuticals and personal care products (PPCPs) by a variety of crops, few studies have assessed the effects of exposure to complex, realistic wastewater effluents on uptake. Hence, in this study, a greenhouse experiment was conducted in order to study the interactions occurring exclusively between PPCPs in soil, and in the edible plant part of beets (Beta vulgaris) after exposure to treated wastewater effluent. According to the findings, the interactions between the pharmaceuticals caffeine (CFN) with bisoprolol (BSP), carbamezapine (CMZ), clarithromycin (CMC), metoprolol (MPL), sulfamethoxazole (SMX), and trimethoprim (TMP) occurring in soil were almost 99% synergistic; it was noted variability in the interactive capacity of the pharmaceuticals; the concentrations of pharmaceuticals which measured did not affect unfavorably beet yield; interactions between the PPCPs via the PPCPs contribution in plant and soil affect the qualitative and quantitative characteristics of the beets., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The use of antioxidants has become a common practice in the development of antiaging cosmetics., Objective: The aim of this study was to evaluate the clinical efficacy of cosmetic formulations containing lycopene and melatonin antioxidants., Method: Thirty-six healthy women from 32 to 65 years were enrolled in this study. The study was carried out for 10 weeks, 2 preconditioning weeks with a control cream without antioxidants, and 8-week test with creams containing antioxidants in study. A multifunctional skin physiology monitor (Courage & Khazaka electronic GmbH®, Germany) was used to measure skin sebum content, hydration, elasticity, erythema index, and melanin index in 4 different regions of the face., Results: There were significant differences between them., (© 2020 S. Karger AG, Basel.)

The widespread distribution of pharmaceuticals and personal care products (PPCPs), particularly in the built environment, has led to increased concern about their effects on both human and ecosystem health. In this research, we investigated the role of algae species Scenedesmus obliquus and Chlorella vulgaris in governing PPCP transfer and transformation mechanisms in algae-containing environments. Lab-scale algal bioreactors were created under various conditions of light, water matrix, and sterilization method to isolate and elucidate reaction mechanisms affecting carbamazepine, ibuprofen, gemfibrozil, and triclosan. The parent compounds and their potential transformation products were analyzed in both the water and algae phases. The results showed that ibuprofen was primarily biotransformed due to synergistic relationships between the algae and the bacteria. Ibuprofen biotransformation products tentatively identified as hydroxy-ibuprofen, carboxy-ibuprofen, and 4-isobutylcatechol were detected in several samples. In all the reactors exposed to light, triclosan underwent both phototransformation and biotransformation. Triclosan biotransformation took place in Scenedesmus obliquus, as demonstrated by the presence of triclosan-O-sulfate in the algae extracts. No evidence of significant carbamazepine and gemfibrozil transfer or transformation was observed under the experimental conditions tested. These results suggest that microalgal-bacterial consortia can facilitate PPCP transformation in algae-based passive water treatment systems., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Organophosphate esters (OPEs) are widely detected among U.S. pregnant women. OPEs, some of which are present in nail polish, have been associated with adverse reproductive health outcomes. More research is needed to investigate associations with OPEs and personal care products (PCP) use., Methods: Pregnant women (18-40 years) were recruited from two hospitals and five prenatal clinics in Northern Puerto Rico (n = 148 women) between 2011 and 2015. Concentrations of bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), di-benzyl phosphate (DBzP), di-cresyl phosphate (DCP), DPHP, and 2,3,4,5-tetrabromobenzoic acid (TBBA) were measured twice during pregnancy. Participants completed questionnaires on PCP and household products (HP) use. Associations among products and metabolite concentrations (n = 296 observations) were assessed using linear mixed models., Results: BCEtP, BCPP, BDCPP and DPHP were detected frequently (≥77%). Correlations among metabolites (0.16 ≤ r ≤ 0.35) and Intraclass correlation coefficients (ICCs) (0.03 ≤ ICC≤0.34) were weak-to-moderate. Suntan lotion was associated with a 110% increase in BDCPP. DPHP increased with perfume (51%) and nail polish (49%) use. BCPP increased 46% with pesticide use in home., Conclusion: Biomarkers of OPEs were often detected among pregnant women. Associations with PCP and HP use suggest OPEs may be used in such products, specifically in perfume and nail polish. Further investigation into these products is warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pharmaceuticals and personal care products (PPCPs) are a group of emerging environmental micropollutants, including prescription drugs and over-the-counter drugs (e.g., antibiotics, synthetic musk, painkiller, depressor, contraceptive drugs, soporific and weight-loss drug), and personal care products (e.g., cosmetics, synthetic perfume, sunscreen, hair spray, tint and fungicide). Extensive attention has been paid to PPCPs because of their potential negative effects on the environments and human health. Abundant researches have focused on the biodegradation of PPCPs. This review summarizes and discusses the biodegradation method, the diversity of PPCPs-degrading microorganisms, the degradation ability, metabolites and proposed pathways as well as the mechanisms of PPCPs' biodegradation. In addition, prospects for further research on biodegradation of PPCPs are also discussed.

Parabens are a kind of preservatives widely used in cosmetic and personal care products and ubiquitously detected in the environment. However, little is known on human exposure to these chemicals. Our study mainly investigated the urinary parabens in adults from South China to evaluate the cumulative risk of paraben exposure. A total of 562 urine samples were collected from adult workers for the determination of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), butyl paraben, and benzyl parabens. High detection frequencies (≥98%) were observed for MeP, EtP, and PrP with median concentrations of 8.88, 5.11, and 1.44 μg/L, respectively. Urinary parabens was 4.5-46.2 fold higher in urine of females than those in males. Urinary MeP was associated with alcohol drinking and a history of tumor, while urinary PrP was negatively associated with education levels of the subjects. There were not significant associations between urinary concentrations of parabens and body mass index, which indicated that obesity was not associated with paraben exposure. Also, parabens did not correlate with human dietary habits. Although the total estimated daily intake (TEDI) of the major compound MeP and EtP in adult workers was lower than the acceptable daily intake (ADI), the TEDI of PrP exceed the ADI for a very few subjects, especially for females and low-educated ones, suggesting potential health risks., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Lignin peroxidase has high potential as ingredient in skin whitening cosmetics due to its high redox potential to oxidize recalcitrant melanin. Currently crude mixtures of lignin peroxidase from fungal fermentation are usually applied to cosmetics due to the intrinsic difficulties of expression and purification. However, the present study focused on heterologous expression and purification of lignin peroxidase isozyme H8 (LiPH8) from Phanerochaete chrysosporium and was further used for melanin decolorization. Results revealed that the optimum pH for melanin decolorization using LiPH8 was obtained at pH 4.0. The intermittent feeding of hydrogen peroxide (H 2 O 2 ) was effectively elevating melanin decolorization efficiency up to 73%, since excessive H 2 O 2 inactivated LiPH8. For cosmetic application, intermittent feeding of H 2 O 2 is not feasible, thus glucose oxidase (GOx) from Aspergillus niger was employed for in-situ generation of H 2 O 2 . By optimizing the GOx and glucose concentrations, a melanin decolorization efficiency up to 63.3 ± 2.4% was obtained within 1 h and continued to 84.0 ± 1.8% in 8 h. Conclusively, lignin peroxidase-catalyzed decolorization of melanin with in-situ generated H 2 O 2 revealed a promising approach for whitening cosmetics applications., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Daidzein is a common isoflavone, having multiple biological effects such as anti-inflammation, anti-allergy, and anti-aging. α-Tocopherol is the tocopherol isoform with the highest vitamin E activity including anti-allergic activity and anti-cancer activity. Hesperetin is a flavone, which shows potent anti-inflammatory effects. These compounds have shortcomings, i.e., water-insolubility and poor absorption after oral administration. The glycosylation of bioactive compounds can enhance their water-solubility, physicochemical stability, intestinal absorption, and biological half-life, and improve their bio- and pharmacological properties. They were transformed by cultured Nicotiana tabacum cells to 7-β-glucoside and 7-β-gentiobioside of daidzein, and 3'- and 7-β-glucosides, 3',7-β-diglucoside, and 7-β-gentiobioside of hesperetin. Daidzein and α-tocopherol were glycosylated by galactosylation with β-glucosidase to give 4'- and 7-β-galactosides of daidzein, which were new compounds, and α-tocopherol 6-β-galactoside. These nine glycosides showed higher anti-allergic activity, i.e., inhibitory activity toward histamine release from rat peritoneal mast cells, than their respective aglycones. In addition, these glycosides showed higher tyrosinase inhibitory activity than the corresponding aglycones. Glycosylation of daidzein, α-tocopherol, and hesperetin greatly improved their biological activities.

Pharmaceuticals and personal care products (PPCPs) are emerging environmental contaminants that can be transformed by anaerobic microorganisms in anoxic environments. The present study examined 2 consortia, enriched under methanogenic and sulfate-rich conditions, that demethylate the phenylmethyl ether anti-inflammatory drug naproxen to 6-O-desmethylnaproxen. Both enriched consortia were also able to demethylate a range of phenylmethyl ether compounds of plant-based origin or used as PPCPs. Results from 16S rRNA gene sequencing showed that the 2 communities were very different despite sharing the same PPCP metabolism. In most cases, the demethylated metabolite was not further degraded but rather accumulated in the culture medium. For the expectorant guaifenesin, this resulted in a novel microbial metabolite. Furthermore, to our knowledge, this is the first report of methylparaben metabolism under methanogenic conditions. The wide range of phenylmethyl ether substrates that underwent O-demethylation in both methanogenic and sulfate-rich conditions suggests that there are potentially bioactive transformation products in the environment that have not yet been quantified. Environ Toxicol Chem 2019;38:1585-1593. © 2019 SETAC., (© 2019 SETAC.)

The vetiver essential oil from Chrysopogon zizanioides contains fragrant sesquiterpenes used widely in the formulation of nearly 20% of men's cosmetics. The growing demand and issues in the supply have raised interest in the microbial production of the sesquiterpene khusimol, the main compound of the vetiver essential oil due to its woody smell. In this study, we engineered the biosynthetic pathway for the production of (+)-zizaene, the immediate precursor of khusimol. A systematic approach of metabolic engineering in Escherichia coli was applied to modulate the critical bottlenecks of the metabolic flux towards (+)-zizaene. Initially, production of (+)-zizaene was possible with the endogenous methylerythritol phosphate pathway and the codon-optimized zizaene synthase (ZS). Raising the precursor E,E-farnesyl diphosphate supply through the mevalonate pathway improved the (+)-zizaene titers 2.7-fold, although a limitation of the ZS supply was observed. To increase the ZS supply, distinct promoters were tested for the expression of the ZS gene, which augmented 7.2-fold in the (+)-zizaene titers. Final metabolic enhancement for the ZS supply by using a multi-plasmid strain harboring multiple copies of the ZS gene improved the (+)-zizaene titers 1.3-fold. The optimization of the fermentation conditions increased the (+)-zizaene titers 2.2-fold, achieving the highest (+)-zizaene titer of 25.09 mg L -1 . This study provides an alternative strategy to enhance the terpene synthase supply for the engineering of isoprenoids. Moreover, it demonstrates the development of a novel microbial platform for the sustainable production of fragrant molecules for the cosmetic industry.

Chemicals used in cosmetics must interact with the enzymes for their consumption after entering our bodies. The area at which the interaction realizes on the enzyme is known as the active center. This center is three dimensional and optically active. Considering the properties of the active regions, it is believed that the determination of the geometric properties of the chemicals may contribute to the safety evaluation of the chemical products. Obtainment of toxicological data of chemicals is a long and difficult process. It is an impossible process as the animal experiments have been prohibited. Since there are large number of chemical compounds available, it is not possible to conduct toxicological evaluation on all of them. Therefore, it is important to estimate whether chemicals are toxic through using molecular formulas. In this study, the similarities and differences between the unwanted chemicals used in cosmetic products and the geometric structures of the chemicals used in metabolism were determined by using Group Theory. The aim of the study is to estimate whether the chemicals will be toxic by taking advantage of point-group determinations. Molecular formulae of chemicals prohibited in cosmetics and substrates used in biological systems were used as materials. The point groups of the molecules were determined using these formulas. ChemDraw Professional 17 chemical drawing program was used to draw the formula structures of the molecules. Campus Licensed version of the program provided by Atatürk University was utilized. An Excel application which was developed to examine the molecules according to the Group Theory was also used., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We used a hybrid precipitation method to simultaneously extract and analyze 24 personal care products (PCPs), including 16 biocides, 4 synthetic musks, and 4 benzotriazoles, in the plasma of fish. The method's performance was validated for plasma samples with and without β-glucuronidase/aryl-sulfatase hydrolysis. The recoveries were in the range of 70-120% for most of the PCPs, except N,N-diethyl-3-methylbenzamide (DEET), clotrimazole (CTZ), miconazole and itraconazole at spiking concentration of 20 and 5 ng/mL. The quantification limits ranged between 0.89 and 17.9 ng/mL (hydrolyzed plasma) and 0.85-18.5 ng/mL (non-hydrolyzed plasma), except CTZ at 77.5 ng/mL and 76.3 ng/mL. Totally, 13 PCPs were detected in plasma samples of fish collected from the Yangtze River, with a maximum concentration of 58.4 ng/mL (galaxolide). Compounds with the phenol hydroxyl groups of parabens or triclosan in hydrolyzed plasma showed higher concentrations than those in unhydrolyzed plasma with the ratio of conjugation (glucuronides + sulfates) forms up to 86%. The median values for the logarithm of bioaccumulation factors were between 1.39 and 4.15, which were 2-3 orders of magnitude higher than the theoretical logarithm of bioconcentration factors. Using the fish plasma model, the effect ratios (effect concentration/measured plasma concentration ratios) of tonalide, galaxolide, benzotriazole, triclosan, and DEET reached 0.35, 4.15, 3.78, 7.52, and 9.24, respectively. These are recognized as priority chemicals for further risk assessment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

It is well known that terrestrial environments host an immense microbial biodiversity. Exposed to different types of stress, such as UV radiation, temperature fluctuations, water availability and the inter- / intra-specific competition for resources, terrestrial microorganisms have been evolved to produce a large spectrum of bioactive molecules. Bacteria, archaea, protists, fungi and algae have shown a high potential of producing biomolecules for pharmaceutical or other industrial purposes as they combine a sustainable, relatively low-cost and fast-production process. Herein, we provide an overview of the different bioactive molecules produced by terrestrial microorganisms with skin protecting applications. The high content in polyphenolic and carotenoid compounds produced by several strains, as well as the presence of exopolysaccharides, melanins, indole and pyrrole derivatives, mycosporines, carboxylic acids and other molecules, are discussed in the context of their antioxidant, photo-protective and skin-whitening activity. Relevant biotechnological tools developed for the enhanced production of high added value natural products, as well as the protecting effect of some antioxidant, hydrolytic and degrading enzymes are also discussed. Furthermore, we describe classes of microbial compounds that are used or have the potential to be used as antimicrobials, moisturizers, biosurfactants, pigments, flavorings and fragrances.

Pharmaceuticals and personal care products (PPCPs) is an important class of environmental contaminants and has gained increasing concerns in recent years. The bioaccumulation behaviour of PPCPs in wetland plants is not well understood. In the present study we report results of a field investigation to assess the bioaccumulation behaviour and phytoremediation efficacy of several PPCPs in Lorong Halus Wetland, a large-scale constructed wetland system in Singapore, constructed for the treatment of landfill leachate. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based methods were employed to quantify concentrations of target PPCPs in leachate and flowing water, as well as wetland plants (roots and shoots), at different locations in the wetland system. The results indicated the presence of several PPCPs in leachate, water and vegetation in the wetland. Bioconcentration factors (BCFs) in the dominant wetland plant, Typha angustifolia, ranged between approximately 60 and 2000. Results indicated that Cattail Typha angustifolia was capable of remediating PPCPs to various extends, with bioconcentration factors ranging up to 2000. The suitability for phytoremediation depends on the physical chemical properties such as hydrophilicity and lipophilicity of these PPCPs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Although the olfactory receptor OR2AT4 was described as involved in epidermal renewal, there is no data about a cosmetic active ingredient activating this receptor. The aim of this research work was thus to identify a natural molecule binding to this receptor in order to stimulate keratinocyte migration., Methods: For this purpose, natural molecules were extracted from Cocos nucifera flour. Then, efficacy of this natural extract was evaluated on keratinocyte migration in vitro. Molecules of the Cocos nucifera flour extract were then identified by UPLC-MS/MS. Molecular docking was finally conducted to investigate the potential interaction between identified molecules and the olfactory receptor OR2AT4., Results: The Cocos nucifera flour extract significantly increased keratinocyte migration and results demonstrated that this effect was mediated by the olfactory receptor OR2AT4. Metabolomic analysis revealed two molecules, nonioside D and butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, as significantly present in the Cocos nucifera flour extract compared to both Cocos nucifera oil and water. Finally, molecular docking revealed that butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside could interact with the extracellular domain 2 of the OR2AT4., Conclusion: This study highlighted for the first time a natural molecule, extracted from Cocos nucifera flour, able to interact with the olfactory receptor OR2AT4 and promote the keratinocyte migration and thus the epithelialization., (© 2019 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

The Threshold of Toxicological Concern (TTC) is an important risk assessment tool which establishes acceptable low-level exposure values to be applied to chemicals with limited toxicological data. One of the logical next steps in the continued evolution of TTC is to develop this concept further so that it is representative of internal exposures (TTC based on plasma concentration). An internal TTC (iTTC) would provide threshold values that could be utilized in exposure-based safety assessments. As part of a Cosmetics Europe (CosEu) research program, CosEu has initiated a project that is working towards the development of iTTCs that can be used for the human safety assessment. Knowing that the development of an iTTC is an ambitious and broad-spanning topic, CosEu organized a Working Group comprised a balance of multiple stakeholders (cosmetics and chemical industries, the EPA and JRC and academia) with relevant experience and expertise and workshop to critically evaluate the requirements to establish an iTTC. Outcomes from the workshop included an evaluation on the current state of the science for iTTC, the overall iTTC strategy, selection of chemical databases, capture and curation of chemical information, ADME and repeat dose data, expected challenges, as well as next steps and ongoing work., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study aims in the understanding of the effect of oligo(ethylene glycol)-based biocompatible microgels inner structure on the encapsulation/release mechanisms of different types of cosmetic active molecules. For that, multi-responsive microgels were synthesized using three types of cross-linkers: ethylene glycol dimethacrylate (EGDMA), oligo(ethylene glycol) diacrylate (OEGDA) and N,N-methylenebisacrylamide (MBA). The inner morphology of the microgels synthesized was studied by 1 H-nuclear magnetic resonance ( 1 H NMR) and small-angle neutron scattering (SANS) techniques and no effect of cross-linker type on microgel microstructure was observed in the case of analysing purified microgel dispersions. Moreover, all the microgels synthesized presented conventional swelling/de-swelling behavior as a function of temperature and pH. Two hydrophobic, one hydrophilic, and one macromolecule as cosmetic active molecules were effectively loaded into different microgel particles via hydrophobic interactions and hydrogen-bonding interactions between -OH groups of active molecules and ether oxygens of different microgel particles. Their release profiles as a function of cross-linker type used and encapsulated amounts were studied by Peppas-Sahlin model. No effect of the cross-linker type was observed due to the similar inner structure of all the microgels synthesized., (Copyright © 2018 Elsevier B.V. All rights reserved.)