An environmentally benign process to synthesize vanillin and other substituted phenyl aldehydes using natural phenylpropenes.

The limited vanillin (3a) production from plant sources requires identifying some renewable and sustainable approaches for its synthesis. This study aimed to develop an efficient, eco-friendly process for synthesizing vanillin (3a) from eugenol (1a) and eugenol-rich essential oils. The chemical methodology for vanillin (3a) synthesis involved base-mediated isomerization of eugenol (1a) to isoeugenol (2a), followed by OsO4/NaIO4 mediated oxidation of isoeugenol to vanillin (3a) using different additives such 1,4-diazabicyclo[2.2.2]octane (DABCO) and substituted pyridines in reusable environment-friendly solvents. Use of 2,6-dimethylpyridine and 2,6-dimethylpyridine N-oxide as additives in the oxidation step offered a significantly higher product yield (vanillin 3a, 70 %). The process synthesized vanillin (3a) irrespective of the cis/ trans stereochemistry of isoeugenol (2a). The peculiarity of the method relates to converting eugenol (1a) to vanillin (3a) without phenolic group protection, which offers step economy. Besides efficient vanillin (3a) synthesis, the process's general implications involve converting other naturally occurring phenylpropenes or phenylpropenes-enriched oils to the corresponding phenyl aldehydes (59-82 % yield).

Zero-waste multistage utilization of dandelion root.

Introduction: In the fragrance and perfume industry, the controlled release of fragrances are crucial factors that contribute to consumer appeal and product quality enhancement. In this study, various aromatic active substances were extracted from dandelion root (DR), which was subsequently calcined to produce high-performance porous biochar material. Methods: The dandelion root biochar (DRB) material was identified as promising adsorbents for the controlled release of fragrances. Furfuryl alcohol was chosen as the model fragrance for inclusion and controlled release studies. Results and discussion: The DRB exhibited a substantial specific surface area of 991.89 m2/g, facilitating efficient storage and controlled release capabilities. Additionally, the DRB's high stability and porous nature facilitated rapid collection and efficient recyclability. This research significantly contributes to the development of a sustainable, zero-waste multistage utilization strategy for dandelion roots, indicating a potential applications in the food flavoring industry and environmental conservations.

Applications of Ene-Reductases in the Synthesis of Flavors and Fragrances.

Flavors and fragrances (F&F) are interesting organic compounds in chemistry. These compounds are widely used in the food, cosmetic, and medical industries. Enzymatic synthesis exhibits several advantages over natural extraction and chemical preparation, including a high yield, stable quality, mildness, and environmental friendliness. To date, many oxidoreductases and hydrolases have been used to biosynthesize F&F. Ene-reductases (ERs) are a class of biocatalysts that can catalyze the asymmetric reduction of α,ß-unsaturated compounds and offer superior specificity and selectivity; therefore, ERs have been increasingly considered an ideal alternative to their chemical counterparts. This review summarizes the research progress on the use of ERs in F&F synthesis over the past 20 years, including the achievements of various scholars, the differences and similarities among the findings, and the discussions of future research trends related to ERs. We hope this review can inspire researchers to promote the development of biotechnology in the F&F industry.

Contact sensitization to fragrance mix I and fragrance mix II among European dermatitis patients: A systematic review.

BACKGROUND: Fragrance substances are a frequent cause of contact allergy worldwide. Fragrance exposure varies by sex, age and possibly country, influenced by cosmetic availability, environmental conditions and cultural practices. OBJECTIVES: To systematically review and gather prevalence of sensitization to fragrance mix I (FM I) and fragrance mix II (FM II) in consecutively patch tested European dermatitis patients. METHOD: A total of 4134 publications on patch test results of European dermatitis patients, published from 1981 to 2022, were systematically reviewed according to a previously registered and published PROSPERO protocol. RESULTS: Eighty-four eligible original articles were analysed. Overall prevalence of sensitization to fragrance mix I (FM I) was 6.81% (95% CI: 6.37-7.28), and FM II was 3.64% (95% CI: 3.3-4.01). Sensitization to FM I was most prevalent in Central and Eastern Europe and to FM II in Western Europe. No clear time trends were observed. Among paediatric dermatitis patients, sensitization prevalence for FM I and FM II was 4.09% (95% CI: 3.37-4.96) and 2.17% (95% CI: 1.53-3.07). CONCLUSION: The frequency of positive patch test results for both FMI and FMII remains high. Sensitization is also prevalent among children. Enhanced regulation and labelling of cosmetic products play a vital role in averting exposure and sensitization to fragrance allergens.

Managing Contact Dermatitis Without Patch Testing.

Allergic contact dermatitis (ACD) is a common skin condition caused by contact with an exogenous agent that elicits an inflammatory response. Patch testing (PT) is considered the gold standard for diagnosing ACD. Unfortunately, PT may not be available to some patients due to insurance and financial limitations, contributing to health care disparity and leaving patients with undiagnosed, incompletely managed dermatitis that can have further detrimental health and occupational effects. For other patients, PT is precluded by lack of availability of specialist/expert care, comorbid medications, or diffuse disease. This article will present a patient with ACD and will work through the differential diagnosis and share strategies for empiric avoidance of suspected/common triggers. The epidemiology of ACD with respect to race and ethnicity, considerations for affordability of hypoallergenic products, access to testing, and the need for future research are addressed in this article.

Fragrance Encapsulates: Effect of Polymeric Shell Purification Method on the Accuracy of Biodegradability Testing.

Fragrance encapsulates are widely used in consumer care applications such as fabric softeners or other liquid laundry products; they provide multiple benefits, from fragrance protection in the commercial product to a controlled release and improved sensorial experience for the consumers. Polymeric fragrance encapsulates are in the scope of the EU regulation restricting the use of intentionally added microplastic particles, and industry is actively working on innovation programs to find biodegradable alternatives. However, particular attention needs to be paid to claims that a fragrance encapsulation system is biodegradable, because biodegradation test results can vary considerably depending on how a test material is prepared, which can even lead to false-positive biodegradation test results, as shown in our study. We demonstrate the importance of the sample preparation phase of the process. We show how the biodegradation level can fluctuate from 0% to 91%, depending on how the test material is isolated from a given microcapsule slurry system, and we present a method that can be used to obtain trustworthy biodegradation results. Environ Toxicol Chem 2024;43:1242-1249. © 2024 Givaudan France SAS. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Plastic Litter Emits the Foraging Infochemical Dimethyl Sulfide after Submersion in Freshwater Rivers.

Plastic pollution is widespread throughout aquatic environments globally, with many organisms known to interact with and ingest plastic. In marine environments, microbial biofilms that form on plastic surfaces can produce the odorous compound dimethyl sulfide (DMS), which is a known foraging cue. This has been shown to increase the ingestion of plastic by some invertebrates and therefore act as a biological factor which influences the risks of plastic to marine ecosystems. In freshwater however, the production of DMS has been largely overlooked, despite the known sensitivity of some freshwater species to this compound. To address this gap, the present study analyzed the production of DMS by biofilms which formed on low-density polyethylene and polylactic acid films after 3 and 6 weeks of submersion in either a rural or an urban United Kingdom river. Using gas chromatography-mass spectrometry, the production of DMS by these biofilms was consistently identified. The amount of DMS produced varied significantly across river locations and materials, with surfaces in the urban river generally producing a stronger signal and plastics producing up to seven times more DMS than glass control surfaces. Analysis of biofilm weight and photosynthetic pigment content indicated differences in biofilm composition across conditions and suggested that DMS production was largely driven by nonphotosynthetic taxa. For the first time this work has documented the production of DMS by plastic litter after submersion in freshwater rivers. Further work is now needed to determine if, as seen in marine systems, this production of DMS can encourage the interaction of freshwater organisms with plastic litter and therefore operate as a biological risk factor in the impacts of plastic on freshwater environments. Environ Toxicol Chem 2024;43:1485-1496. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Analysis of preservatives and fragrances in topical medical devices: The need for more stringent regulation.

INTRODUCTION: Medical devices (MDs) have a long history of use, and come with regulatory frameworks to ensure user safety. Although topically applied MDs in the form of gels and creams might be used on damaged skin, their composition is often similar to that of cosmetic products applicable to intact skin, especially in terms of preservatives and fragrances. However, unlike cosmetics, these products are not subject to compound-specific restrictions when used in MDs. OBJECTIVE: This study aimed to identify and quantify preservatives and fragrances in topically applied MDs and assess their safety towards the Cosmetic Regulation (EC) 1223/2009. METHOD: Sixty-nine MDs available on the EU market were subjected to previously validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods to identify and quantify occurring preservatives and fragrances. RESULTS: Findings revealed that 32% of the examined MDs did not provide comprehensive ingredient lists, leaving users uninformed about potential risks associated with product use. Furthermore, 30% of these MDs would not meet safety standards for cosmetic products and, most significantly, 13% of the analysed samples contained ingredients that are prohibited in leave-on cosmetics. CONCLUSION: Results highlight the pressing demand for more stringent requirements regarding the labelling and composition of MDs to enhance patient safety. Improved regulation and transparency can mitigate potential risks associated with the use of topically applied MDs.

Mass-Spectrometry-Based Research of Cosmetic Ingredients.

Cosmetic products are chemical substances or mixtures used on the skin, hair, nails, teeth, and the mucous membranes of the oral cavity, whose use is intended to clean, protect, correct body odor, perfume, keep in good condition, or change appearance. The analysis of cosmetic ingredients is often challenging because of their huge complexity and their adulteration. Among various analytical tools, mass spectrometry (MS) has been largely used for compound detection, ingredient screening, quality control, detection of product authenticity, and health risk evaluation. This work is focused on the MS applications in detecting and quantification of some common cosmetic ingredients, i.e., preservatives, dyes, heavy metals, allergens, and bioconjugates in various matrices (leave-on or rinse-off cosmetic products). As a global view, MS-based analysis of bioconjugates is a narrow field, and LC- and GC/GC×GC-MS are widely used for the investigation of preservatives, dyes, and fragrances, while inductively coupled plasma (ICP)-MS is ideal for comprehensive analysis of heavy metals. Ambient ionization approaches and advanced separation methods (i.e., convergence chromatography (UPC2)) coupled to MS have been proven to be an excellent choice for the analysis of scented allergens. At the same time, the current paper explores the challenges of MS-based analysis for cosmetic safety studies.

Sniffing Out the Sustainable Future: The Renewability Revolution in Fragrance Chemistry.

In this review, the impact of the transition from today's resource-wasting petrochemical economy towards a 100/100 renewable and biodegradable future is discussed with respect to the fragrance families: "citrus", "green", "fruity", "floral", "floriental", "oriental", "woody", "chypre" and "fougère". After benchmark data on ingredients usage, definitions on biodegradation and sustainability are given. Celebrating the 150th anniversary of synthetic vanillin, its historic synthesis from renewable starting materials serves as introduction. In the grand scheme of things, citrus scents upcycled from the beverages industry, are already an ideal case for 100/100 with new opportunities for artificial essential oils. In the fruity domain, transparent and lactonic ingredients are available in a sustainable manner. However, in the domain of green odorants, there is a lack of green chemistry for important key materials. In the floral family, renewability is more critical than biodegradability, but cost is an issue. Thanks to Ambrox and maltol, florientals and orientals will persist, while woody notes severely lack an Iso E Super replacer. In the chypre genre, patchouli became the new moss, but more musks are increasingly in demand. With their high percentage of linalool and dihydromyrcenol, the construction of fougères could well become a precedent for other families, despite challenges in vetiver and salicylates. Still, the challenges exemplified here create immense opportunities for new perfumery materials.

Aromas: Lovely to Smell and Nice Solvents for Polyphenols? Curcumin Solubilisation Power of Fragrances and Flavours.

Natural aromas like cinnamaldehyde are suitable solvents to extract curcuminoids, the active ingredients found in the rhizomes of Curcuma longa L. In a pursuit to find other nature-based solvents, capable of solving curcumin, forty fragrances and flavours were investigated in terms of their solubilisation power. Aroma compounds were selected according to their molecular structure and functional groups. Their capabilities of solving curcumin were examined by UV-Vis spectroscopy and COSMO-RS calculations. The trends of these calculations were in accordance with the experimental solubilisation trend of the solubility screening and a list with the respective curcumin concentrations is given; σ-profiles and Gibbs free energy were considered to further investigate the solubilisation process of curcumin, which was found to be based on hydrogen bonding. High curcumin solubility was achieved in the presence of solvent (mixtures) with high hydrogen-bond-acceptor and low hydrogen-bond-donor abilities, like γ- and δ-lactones. The special case of DMSO was also examined, as the highest curcumin solubility was observed with it. Possible specific interactions of selected aroma compounds (citral and δ-hexalactone) with curcumin were investigated via 1H NMR and NOESY experiments. The tested flavours and fragrances were evaluated regarding their potential as green alternative solvents.

The scent of roses, a bouquet of fragrance diversity.

Roses have been domesticated since antiquity for their therapeutic, cosmetic, and ornamental properties. Their floral fragrance has great economic value, which has influenced the production of rose varieties. The production of rose water and essential oil is one of the most lucrative activities, supplying bioactive molecules to the cosmetic, pharmaceutical, and therapeutic industries. In recent years, major advances in molecular genetics, genomic, and biochemical tools have paved the way for the identification of molecules that make up the specific fragrance of various rose cultivars. The aim of this review is to highlight current knowledge on metabolite profiles, and more specifically on fragrance compounds, as well as the specificities and differences between rose species and cultivars belonging to different rose sections and how they contribute to modern roses fragrance.

Detection of fragrances on the skin and study of their interaction using infrared and Raman spectroscopy.

Nowadays, fragrances belong to the widely used cosmetics. Their composition is designed in a way that it evolves and changes over time. In this work, the effect of fragrances on the skin was studied - the interactions between pig skin samples and fragrances and the possibility of their detection and mutual differentiation. Non-invasive techniques of vibrational spectroscopy were used to obtain the data, namely FT-IR spectroscopy with attenuated total reflection accessory and Raman microspectroscopy. Vibrational spectra were measured within 8 h with different time intervals and after 22 h from the application of fragrance for FT-IR and Raman measurements, respectively. The obtained spectra were pre­processed and subsequently evaluated by multivariate statistical methods. The study showed that skin treated by fragrances is well distinguishable from untreated skin, even after 22 h. In addition, it is possible to differentiate individual fragrances from each other; therefore, the use of spectroscopical techniques could be a potential tool for forensic analysis of fragrances.

Frequency and clinical relevance of contact allergy in dental patients.

BACKGROUND: While many studies have reported on occupational allergic contact dermatitis amongst dental personnel, studies on the relevance of patch testing in dental patients are scarce. OBJECTIVES: To determine the frequency and clinical relevance of contact allergy in patients with intra- and perioral complaints. METHODS: A total of 360 patients with intra- and perioral complaints suspected of having a contact allergy were patch-tested with the dental allergen series, European Baseline Series, and extended Amsterdam Baseline Series at Amsterdam University Medical Centers between January 2015 and November 2021. RESULTS: A total of 285 patients (79.2%) had a positive patch test reaction for either one (18.6%) or multiple allergens (60.6%). Sodium tetrachloropalladate was the most sensitising allergen with 98 patients (27.2%) testing positive, followed by nickel sulphate (23.3%), methylisothiazolinone (15.6%), and fragrance mix I (14.2%). Clinical relevance was found in 68 of 208 patients (32.7%), with patients having one (15.4%) or multiple (17.3%) patch test reactions clinically relevant to their (peri)oral complaints. CONCLUSIONS: Clinically relevant patch test reactions were frequently seen in dental patients. Although this study provides us with a better understanding on the frequency and clinical relevance of contact allergy in dental patients, further studies are needed to confirm our results.

Biotechnology - A Tool to Transform Givaudan's Fragrance Ingredients Palette.

To support perfumers in their creation of olfactive signatures resulting in unique and instantly recognizable perfumes, there is a constant demand for the development of new odorant molecules and of novel processes for their production. Increasing the sustainability of both the molecules and the processes is a crucial activity at Givaudan. Biocatalysis has the potential to positively influence metrics applied at Givaudan that drive and measure our ambition to innovate responsibly, which is summarized in the FiveCarbon Path™. It targets an increased use of renewable carbon, carbon efficiency in synthesis, and the production of powerful and biodegradable odorant molecules while maximizing the use of upcycled carbon available from waste and side streams. This review illustrates with some examples how enzymes selected from the oxidoreductase and isomerase enzyme classes are applied at Givaudan for the preparation of odorant molecules both at laboratory and industrial scale.

Forgotten Perfumery Plants - Part II: New Insights into the Development of Novel Fragrant Ingredients - Hawthorn Case Study.

Naturalness is gaining ground among perfumers and the use of natural raw materials is spreading in perfumery. Forgotten perfumery plants are of concern to develop innovative and natural ingredients for modern perfume industries. The main purpose of this study was to evaluate the potential interest of Crataegus monogyna Jacq. extracts as fragrance ingredient. To this end, various extractions, phytochemical characterizations and organoleptic evaluations of hawthorn were conducted on fresh, frozen, and dried flowering aerial parts, to identify those most likely to be of interest. More than a hundred compounds, anisaldehyde being the predominant one, were characterized for the first time in the volatile fraction, using HS-SPME-GC-MS technology. Impact of plant treatment and harvest year on the extracts were also discussed. From this work, a new and natural hawthorn-based ingredient was developed to complete the perfumers' palette.

Glacier foreland insect uptake synthetic compounds: an emerging environmental concern.

Pesticides, synthetic fragrances and polycyclic aromatic hydrocarbons contaminated two glacier-fed streams (Amola, Mandrone) and one spring (Grostè) in the Italian Alps. Ten compounds (chlorpyrifos (CPY), chlorpyrifos-methyl (CPY-m), galaxolide (HHCB), tonalide (AHTN), fluorene (Flu), phenanthrene (Phen), anthracene (Ant), fluoranthene (Fl), pyrene (Pyr), benzo[a]anthracene (BaA)) accumulated in aquatic larvae of chironomids (Diamesa steinboecki, D. latitarsis, D. bertrami, D. tonsa, D. zernyi, Pseudokiefferiella parva, Orthocladiinae) and tipulids. Their tissue concentrations (detected by gas chromatography coupled with mass spectrometry) ranged from 1.1 ± 0.1 ng/g d.w. (= dry weight) (CPY-m in D. tonsa from Amola) to 68.0 ± 9.1 ng/g d.w. (Pyr in D. steinboecki from Mandrone). HHCB, AHTN, and CPY, with one exception, were accumulated by all aquatic insects. Six compounds (CPY, CPY-m, HHCB, AHTN, Fl, Pyr) also contaminated carabids (Nebria germarii, N. castanea, N. jockischii) predating adults of merolimnic insects. Their tissue concentrations ranged from 1.1 ± 0.3 ng/g d.w. (CPY-m in N. germarii from Mandrone) to 84.6 ± 0.3 ng/g d.w. (HHCB in N. castanea from Grostè). HHCB and AHTN were accumulated by all Nebria species. Intersite and interspecies differences were observed, which might be attributed to different environmental contamination levels. There was a stronger similarity between species from the same site than among the same species from different sites, suggesting that uptake is not species specific. At all sites, the concentration of xenobiotics was higher in larvae than in water and comparable or higher in carabids than in larvae from the same site, suggesting trophic transfer by emerging aquatic insects to their riparian predators.

Enzymatic properties of a non-classical aldoxime dehydratase capable of producing alkyl and arylalkyl nitriles.

Nitriles are of significant interest in the flavor and fragrance industries with potential application in cosmetics due to their higher stability than analogous aldehydes. However, the traditional methods to prepare nitriles need toxic reagents and hash conditions. This work aimed to develop a chemoenzymatic strategy to synthesize nitriles from natural aldehydes with aldoxime as the intermediate. A non-classical aldoxime dehydratase (Oxd) was discovered from the fungus Aspergillus ibericus (OxdAsp) to catalyze the dehydration of aldoximes to corresponding nitriles under mild conditions. The amino acid sequence of OxdAsp exhibits an approximately 20% identity with bacterial Oxds. OxdAsp contains a heme prosthetic group bound with the axial H287 in the catalytic pocket. The structure models of OxdAsp with substrates suggest that its catalytic triad is Y138-R141-E192, which is different from the classically bacterial Oxds of His-Arg-Ser/Thr. The catalytic mechanism of OxdAsp was proposed based on the mutagenesis of key residues. The hydroxyl group of the substrate is fixed by E192 to increase its basicity. Y138 acts as a general acid-based catalyst, and its phenolic proton is polarized by the adjacent R141. The protonated Y138 would donate a proton to the hydroxyl group of the substrate and eliminate a water molecule from aldoxime to produce nitrile. The recombinant OxdAsp can efficiently dehydrate citronellal oxime and cinnamaldoxime to citronellyl nitrile and cinnamonitrile in aqueous media, which are applied as fragrance ingredients in the food and cosmetic fields. KEY POINTS: • A novel aldoxime dehydratase from the Aspergillus genus was first characterized as a heme-binding protein. • The catalytic mechanism was predicted based on the molecular interactions of the catalytic pocket with the substrate. • A chemoenzymatic strategy was developed to synthesize nitriles from natural aldehydes with aldoxime as the intermediate.

Fragrance allergens in cosmetic products marketed for children in Denmark.

BACKGROUND: Fragrances are among the most common contact allergens in children. Cosmetic products are the most frequent source of skin exposure. OBJECTIVE: To investigate exposure to fragrance allergens among Danish children, based on a sample of 1179 cosmetic products marketed for children. METHODS: Information regarding cosmetic products marketed to children was obtained using a non-profit smartphone application registry, with data from December 2015 to November 2022. RESULTS: The number of validated products was 26 537, of which 1349 marketed for children. After elimination of duplicates, 1179 (4.4%) individual products remained. The majority 53.8% (634/1179) of the products were fragranced. The highest frequency of declared fragrances was found in 'Facial care'-products: 93.0% (80/86), of which 97.7% were lip balms. The highest number of labelled fragrances in one single product (n = 16) was found in a baby perfume. Fragrance mix I (FMI) or II (FMII) allergens were found in 25.3% (298/1179) of the products. Limonene and linalool were the two most frequently labelled fragrance allergens. CONCLUSION: Children can be exposed to a vast number of fragrance allergens from scented cosmetic products. Allergens from FM I and FMII are widely used in cosmetic products marketed to children. Patch testing with FMI and FMII remains relevant in children.