PHENOXYETHANOL

Neonatal sepsis causes substantial mortality. Topical antisepsis for laboring women or neonates may reduce pathogenic colonization and sepsis risk. To evaluate the safety and effectiveness of various topical antiseptic regimens to reduce bacterial load in the maternal genital tract and on neonatal skin and assess suitability for future effectiveness trials. This randomized clinical trial was conducted from March 7, 2022, to March 29, 2023, at Zomba Central Hospital, Malawi, with 28-day follow-up. Participant populations were laboring women and, separately, facility-born neonates (aged <24 hours and with birth weight >1000 g) not born to a mother recruited to the trial. Data were analyzed from May 17 to December 28, 2023. Participants were individually randomized in an unblinded factorial design to chlorhexidine 1% (1% CHG), chlorhexidine 2% (2% CHG), or octenidine 0.1% with phenoxyethanol 2% (OHP), each applied either once or multiple times (maternal: antiseptic applied every 4 hours during working hours for up to 6 applications; neonatal: antiseptic applied every 24 hours for up to 3 applications), or to standard of care (SOC; application of sterile water for mothers and no cleansing for neonates). Laboratory staff assessing primary outcomes were blinded. Co-primary outcomes were change in total skin bacterial load (log10 colony-forming units [log10CFU]) from baseline at each follow-up, analyzed separately in the maternal and neonatal populations and adjusted for intervention variables. Secondary outcomes included skin condition score (range, 0-12 for neonates and 0-16 for women; lower scores indicate better condition), serious adverse events (SAEs), and neonatal temperature. A total of 149 women (mean [SD] age at enrollment, 25.7 [5.9] years) and 147 neonates (mean [SD] age at enrollment, 10.3 [6.3] hours; 82 [56%] male) participated. Mean (SD) infant gestational age was 37.7 (1.5) weeks in the maternal population and 36.7 (3.1) weeks in the neonatal population. Neonates' mean birth weight was 2729 g (712 g). Among mothers, compared with 1% CHG, bacterial load was higher (worse) with OHP (adjusted log10CFU difference, 1.7; 95% CI, 0.9-2.5) and SOC (3.5; 95% CI, 2.4-4.6); there was no clear log10CFU difference with 2% CHG (-0.6; 95% CI, -1.4 to 0.2). There was no evidence of difference in effectiveness between multiple vs single application (log10CFU difference, -0.4; 95% CI, -1.1 to 0.2). In neonates, 1% CHG showed greater effectiveness than SOC (log10CFU difference, 1.3; 95% CI, 0.2-2.4) but no difference vs 2% CHG (-0.2; 95% CI, -1.1 to 0.7) or OHP (0.7; 95% CI, -0.2 to 1.6). Multiple applications showed increasing benefits over time (frequency × time interaction). Skin scores were low (almost all were 0-1 and none ≥3). There were no significant differences in SAE rates between arms and no signal of postantiseptic neonatal hypothermia. In this randomized clinical trial of topical antiseptics applied in laboring women and in neonates, 1% CHG reduced maternal and neonatal bacterial colonization without safety concerns, suggesting it would be the optimal regimen to evaluate in a larger pragmatic trial powered for clinical outcomes. ISRCTN Registry Identifier: ISRCTN78026255.

Perseverance is a phenotype in which a small subpopulation of bacteria continues to divide for hours in the presence of antimicrobial concentrations that inhibit bulk population growth, without acquiring genetic resistance. Perseverance has previously been reported only in antibiotic-treated bacteria, but not in preservative-treated bacteria. However, perseverance could limit preservative efficacy, and we investigated this phenomenon in preservative-treated bacteria. Cosmetic products rely on preservatives to control microbial growth; however, preservative types and concentrations are limited for safety reasons, and boosters are often added to enhance efficacy. Some formulations also contain nutrients, such as plant extracts, that promote heterogeneous microbial behavior. Therefore, single-cell analyses are needed to understand these responses and assess preservation risk. In this study, we combined time-lapse microscopy and a microdevice to perform single-cell analysis of Staphylococcus ureilyticus , a potential cosmetic contaminant, when exposed to the preservative 2-phenoxyethanol (PE) and booster ethylenediaminetetraacetate (EDTA). Conventional time-kill assays confirmed that EDTA enhanced the bactericidal effect of PE. Single-cell analysis revealed a subpopulation of cells that underwent up to five divisions over 23.4 h of PE exposure during viable count decline. Pedigree analysis showed that dividing lineages did not share cell fates with their ancestors, supporting a non-mutational perseverance phenotype. Compared with PE alone, the addition of EDTA markedly reduced single-cell division, with most cells dividing once or not at all despite similar population-level kill curves. These results demonstrate that single-cell analysis can reveal microbial behaviors masked in population-based assays and that EDTA may suppress persevering subpopulations that threaten product preservation.IMPORTANCEThis study highlights the significance of investigating the behavior of individual microbes in cosmetic products that employ limited microbial control strategies but may contain ingredients capable of supporting microbial proliferation. Through single-cell analysis of dynamic microbial responses to the preservative phenoxyethanol (PE) and booster ethylenediaminetetraacetate (EDTA), we demonstrate bacterial perseverance in the presence of PE and its suppression by EDTA. By enhancing the bactericidal effects of PE and suppressing perseverance, EDTA reinforces its role as a preservative booster. These findings advance our understanding of preservative performance and provide insights that may improve both the safety and effectiveness of preservatives in cosmetic products.

Moisturising cosmetic products (MCP) formulations may contain ingredients known to trigger allergic contact dermatitis. Claims such as 'hypoallergenic' or 'fragrance-free' are commonly used in marketing, yet these terms are not consistently regulated, potentially posing a risk for patients with allergic contact dermatitis. To assess the allergenic potential of moisturisers by analysing their ingredients and determining the prevalence of contact allergens. A survey conducted between April and June 2023. MCPs were collected from supermarkets and pharmacies. Data analysis focused on allergen prevalence and product origin. All products were systematically screened for seven targeted allergenic components by reviewing their ingredient labels (INCI): isothiazolinones, phenoxyethanol, formaldehyde and its releasers, lanolin, fragrances, parabens and propylene glycol. All allergens included in our study were systematically searched for all relevant synonyms in both English and French. Three hundred products were analysed, including 153 items (51%) from supermarkets and 147 (49%) from pharmacies. Fragrances were the most frequently identified allergens, present in 84.7% of formulations. Only 15.3% of products were free from fragrances and plant extracts. Among those labelled 'fragrance-free', 86.8% (46 of 53) were truly free of fragrances. Isothiazolinones were found in 7% of products, predominantly in leave-on formulations and locally manufactured brands. Formaldehyde-releasing agents were detected in 10.3% of products, with higher prevalence in supermarkets and leave-on items. Parabens were present in 10.7%, including two products with hydroxybenzoate. Propylene glycol was identified in 28% of products; still, 24.3% (18 of 74) of hypoallergenic-labelled products contained it. Phenoxyethanol appeared in 37.7% of formulations and was more common in supermarket-sold products. Lanolin was found in 2.7% of the products. The study highlights a high prevalence of contact allergens in MCPs, including those marketed as hypoallergenic.

Percutaneous penetration is an important human exposure route, but it is influenced by multiple factors and can vary greatly between different substances and exposure conditions. Furthermore, skin characteristics such as thickness of different anatomic sites may have an effect on percutaneous absorption. Despite a potential relevance for safety measures, little is yet known for occupationally relevant skin sites, like hands. We conducted a human in vivo study aiming to identify the effect of anatomic sites on percutaneous absorption of 2-phenoxyethanol. Two human volunteers were dermally exposed to 2-phenoxyethanol (loading dose: 0.2 mg/cm 2 skin) at seven different anatomic skin sites with areas of 200 and 400 cm 2 , respectively. Blood and urine samples were collected and analyzed for 2-phenoxyethanol and its two main metabolites up to 48 h post-exposure. Relative absorption ratios showed moderate site differences ranging from 0.89 to 1.64 (compared to the forearm) as the overall renal recovery was between 23 and 43% of applied 2-phenoxyethanol. Inter-individual variability was in a similar range. A notable influence of the exposed site could, however, be observed for the penetration speed which was highest at the forehead and neck, and slowest at the hand palms. Differing ratios of unmetabolized 2-phenoxyethanol and its main metabolite found in blood point to a site-depending intradermal metabolism. This study revealed major findings concerning the velocity of percutaneous penetration at different skin sites, which is relevant for adequate skin protection. The obtained data broaden the knowledge about site-related variations in percutaneous absorption and thus can improve future toxicological evaluations.

Analytical chemistry plays a central role in research and innovation, yet its environmental impacts remain insufficiently represented in sustainability assessments. Current score-based "greenness" indicators-defined as the compliance to the 12 green analytical chemistry principles-often overlook upstream and downstream processes, such as instrument manufacturing and data management. This study applies life cycle assessment (LCA) to characterize the environmental performance of four representative workflows in a cosmetic industry R&I setting: an untargeted UPLC-PDA/HRMS analysis of natural extracts and three phenoxyethanol quantification methods (GC-MS, HPLC-UV, UPLC-UV). Inventories were structured to distinguish sample preparation, instrumental analysis, and data processing from supporting flows like consumables and energy. The results reveal distinct environmental hotspots for each protocol. The UPLC-PDA/HRMS workflow exhibited a climate change impact of 4.30 kg CO₂eq, driven by the amortization of the devices and the sample transport. In contrast, the GC-MS workflow (3.82 kg CO₂eq) was heavily influenced by dichloromethane production, while the HPLC-UV protocol reached 6.84 kg CO₂eq due to consumable-related flows and longer run times. These findings demonstrate that environmental burdens are highly workflow-specific and that commonly cited factors, such as solvent use, are not always the primary drivers. The study concludes that the normalization factors from the product environmental footprint (PEF) method are inadequate for analytical laboratory contexts and suggests that quantitative LCA provides a necessary complement to score-based metrics like the analytical greenness metric (AGREE) for supporting robust eco-design and corporate sustainability initiatives.

Background: Octenidine-based antiseptics are increasingly used in neonatal and pediatric care for skin antisepsis and wound care, yet their cutaneous safety has not been systematically profiled. Methods: This scoping review, based on JBI methodology, mapped evidence on skin injuries and local complications in neonates and children after octenidine-based use on intact skin or wounds. Results: Of 242 records, six studies, all conducted in Europe (Germany 66.7%, Switzerland 16.7%, Poland 16.7%), were included ( n =  30 patients). Two studies reported intact-skin antisepsis before procedures in 18 neonates while four papers addressed cleansing of traumatic, surgical, or infectious wounds in 12 infants or children. Formulations were mainly octenidine 0.1% with phenoxyethanol 2% (22/30; 73.3%), with aqueous 0.1% (6/30; 20.0%) and alcohol-based 0.1% (2/30; 6.7%) less frequent. Reported events ranged from transient erythema to bullous/erosive dermatitis, subcutaneous edema, fatty tissue necrosis, and phlegmon-like reactions. Management varied from conservative care to surgery, with scarring or contractures in some cases. Conclusion: The available evidence, limited to case reports, case series, a survey and one small cohort, thereby preventing causal inference and incidence or prevalence estimates due to the absence of denominator data, nonetheless indicates injuries with both aqueous and alcohol-based products, raising concern for a potentially compound-related, rather than vehicle-specific, risk. Clinicians should consider judicious use of octenidine, monitor closely, and consider the potential utility of patch testing for delayed allergic reactions. Priority needs include multicenter studies, standardized skin outcomes, detailed exposure reporting, and pharmacovigilance or registries.

Preservatives are primarily used for their antimicrobial properties and form an important component of food, cosmetic, and drug formulations. The efficacy of preservatives depends on various factors, which include the bacterial membrane composition and the interaction between components of a specific formulation. Molecules such as phenoxyethanol (POE), caprylylglycol (CPG), and methylparaben (MEP) are widely used as preservatives in the food and cosmetic industries; however, a molecular understanding of their interactions with surfactants and the kinetics of membrane partitioning remains unexplored. In this study, coarse-grained molecular dynamics simulations were carried out to evaluate and quantify the kinetics of membrane partitioning for preservatives and surfactants in the Escherichia coli inner phospholipid membrane. We propose a mass-transfer-based model to determine membrane partitioning kinetics. Faster kinetics were observed for first-order partitioning of POE and MEP (τ ∼ 0.01 μs) when compared with zeroth-order kinetics (τ ∼ 0.1 μs) for CPG. In contrast, surfactants such as sodium laureth sulfate (SLES) and cocamidopropyl betaine (CAPB) follow zeroth-order membrane partitioning kinetics with significantly higher time constants (1.5-10 μs). Interestingly, zeroth-order kinetics occurred when micellar aggregates were present, and the rate-controlling step was the slow rate of release of single molecules from the aggregate, in comparison to faster membrane uptake kinetics. Using a sequential micellar breakup model with single surfactant release dynamics, we analytically recover this unique zeroth-order membrane partitioning kinetics. In preservative-surfactant mixtures, the kinetics of preservative partitioning were found to decrease by a factor of 2-10. Significantly, the equilibrium membrane saturation coefficients for both preservatives and surfactant remained invariant in the mixtures due to the wide separation of partitioning time scales for the surfactants and preservatives. The kinetic models developed in this study can be used to quantify membrane partitioning of preservatives and understand the influence of surfactants in specific formulations.

It has been reported that pregnant women used more cosmetics daily than non-pregnant women. Phenoxyacetic acid is the main metabolite of phenoxyethanol, the most frequent preservative in cosmetics used in Europe, previously associated with reproductive effects (longer time to conception, endocrine disruptors in newborns and poorer verbal comprehension in children). In France, specialised platforms (PREVention ENvIronment Reproduction (PREVENIR)) in university hospital maternity wards are dedicated to evaluating environmental and occupational exposures in patients with pregnancy-related pathologies and supporting targeted prevention efforts. These platforms are composed of occupational health physicians, obstetrician-gynaecologists, midwives, occupational health nurses, and occupational health and environmental engineers. To assess the efficacy of these platforms, we developed a randomised clinical trial, the protocol for which is presented in this paper. The primary objective of the PREVENIR-G Study is to compare the change in urinary phenoxyacetic acid concentrations from baseline to 3 months postintervention between an intervention group and a control group. To date, the intervention has been integrated into routine care in certain facilities; however, its efficacy remains unproven. It is therefore essential to assess the relevance of this intervention, considering both its potential benefits and any adverse effects, such as increased stress or anxiety. This study is an unblinded, randomised clinical superiority trial with two parallel groups (intervention vs no intervention) in four university maternity hospitals in France. We will include 300 pregnant women (aged 18 years or older) who are under 24 weeks of gestation (150 per group) referred to the participating PREVENIR platforms for management. The intervention will consist of clinical prevention management through the PREVENIR platforms, involving a consultation with an environmental health expert for an assessment of environmental and occupational exposures. During the consultation, targeted prevention messages will be provided based on identified exposures. The no intervention comparator will be a waiting-list control group. At the inclusion visit, patients will receive urine collection vials for samples to be collected at baseline and again at 3 months. Urine samples will be collected twice in a single day, on three separate days, during the collection week at home. In the week following the urine collection period, only participants in the intervention group will engage with the PREVENIR platforms. The primary outcome will be the difference in the urinary phenoxyacetic acid concentration between baseline and 3 months postintervention, compared between the intervention and control groups. The study has been approved by the hospital ethics committee (CCP Ouest 2, no. 2023-A00941-44). All participants will provide written informed consent. Results will be shared through presentations and publications. NCT06642818.

Hair growth cosmeceuticals (HGCs) for women have become increasingly popular. We sought to analyze the ingredients of HGCs and their potential environmental hazards. A cross-sectional study was conducted using a Google Boolean search to identify the top 10 nonsponsored articles on HGCs. After applying exclusion criteria, 58 unique HGCs marketed as either unisex or female products were analyzed. Ingredients were documented from product websites, and HGCs were categorized based on specific ingredients with potential environmental concerns. The study found that phenoxyethanol (32.8%) and synthetic fragrances (25.9%) were the most common ingredients with potential environmental implications, with trisodium Ethylenediaminetetraacetic acid (EDTA), trisodium ethylenediamine disuccinate, isobutane, butane, n-butane, ethylhexyl methoxycinnamate, and benzophenone-4 also found. Ingredients such as sodium lauryl sulfate, parabens, and microbeads were, however, not found in any of the products evaluated. The study was limited by potential reporting and sampling bias. Significant environmental hazards, particularly to aquatic habitats, have been associated with specific ingredients commonly found in HGCs.

An analytical method was developed and validated for the simultaneous detection of four glycol ethers in cosmetic creams using headspace gas chromatography coupled with mass spectrometry (HS-GC-MS). Samples were extracted with ethanol and then subjected to vortexing and ultrasonic treatment prior to analysis. The analytes showed good linearity within the concentration range of 25-200 µg/mL, with determination coefficients (R 2 ) exceeding 0.995. Limits of detection (LOD) and quantification (LOQ) were determined for each compound. For ethylene glycol dimehyl ether (EGDME), LOD and LOQ were 1.39 and 4.00 µg/mL, respectively. For diethylene glycol monoethyl ether (DEGEE), values were 3.70 and 12.34 µg/mL. Triethylene glycol dimethyl ether (TEGDME) showed LOD and LOQ of 1.61 and 5.38 µg/mL. For phenoxyethanol (EGPhE), these limits were 4.79 and 15.95 µg/mL. Mean recovery rates ranged from 96.72% to 100.40%, and relative standard deviations (RSDs) remained below 15% across all validation procedures. The average method recovery ranged between 100.34% and 102.09%. The validation parameters, including specificity, linearity, precision, trueness, and accuracy, were found to be satisfactory.