Daily Cosmetic Research Analysis
Three studies advance cosmetic and dermatologic science from safety to mechanism and methods: a PBTK-integrated assessment shows rapid systemic uptake of VOCs from feminine hygiene products; gluconic acid mechanistically suppresses hypertrophic scarring via PLOD1 targeting and AKT/mTOR-autophagy modulation; and an ex vivo human/rat sweat gland model enables reliable calcium imaging and cryopreservation, facilitating antiperspirant discovery without animal testing.
Summary
Three studies advance cosmetic and dermatologic science from safety to mechanism and methods: a PBTK-integrated assessment shows rapid systemic uptake of VOCs from feminine hygiene products; gluconic acid mechanistically suppresses hypertrophic scarring via PLOD1 targeting and AKT/mTOR-autophagy modulation; and an ex vivo human/rat sweat gland model enables reliable calcium imaging and cryopreservation, facilitating antiperspirant discovery without animal testing.
Research Themes
- Consumer product chemical exposure modeling and safety
- Mechanistic anti-scarring therapeutics
- Ex vivo human tissue models for cosmetic testing
Selected Articles
1. Estimation of Dermal Exposure to Volatile Organic Compounds (VOCs) from Feminine Hygiene Products: Integrating Measurement Data and Physiologically Based Toxicokinetic (PBTK) Model.
Using product measurements and a PBTK model, the study shows that dermally absorbed VOCs from feminine hygiene products rapidly peak in most tissues within an hour of use. Inhalation exposure was estimated from 20 air samples, and predicted urinary concentrations were validated against 99 samples from 25 women. The work highlights potentially significant body burdens and recommends integrated toxicokinetic modeling for accurate risk assessment.
Impact: Provides a rigorous, validated framework for internal dose estimation of consumer-product VOCs, informing regulatory policy and exposure mitigation. Integrates dermal and inhalational routes and validates against human biomonitoring.
Clinical Implications: Clinicians can counsel patients, especially those with dermatologic or reproductive concerns, about potential VOC exposures from feminine hygiene products and consider recommending low-VOC alternatives. The framework supports public health guidance and regulatory reformulation efforts.
Key Findings
- Dermal absorption led to rapid peak levels of most target VOCs across tissues within one hour of product use, with adipose tissue behaving differently.
- Inhalation exposure was quantified from 20 passive air samples analyzed by thermal desorption GC-MS.
- Predicted urinary VOC concentrations (from dermal and inhalation inputs) were validated against 99 measurements from 25 women, supporting model credibility.
- The study recommends integrating toxicokinetic modeling with biomonitoring to capture tissue-specific distributions and reduce misclassification.
Methodological Strengths
- Integration of measured product contents with PBTK modeling across multiple tissues and routes.
- External validation of model predictions using human urinary biomonitoring data.
Limitations
- Human validation cohort was relatively small (25 individuals), which may limit generalizability.
- Only eight VOCs and selected product categories were evaluated; broader chemical coverage is needed.
Future Directions: Expand chemical coverage and product categories, include larger and diverse cohorts, refine adipose kinetics, and link internal doses to health outcomes to inform regulatory thresholds.
BACKGROUND: An increasing number of studies have reported noteworthy health risks associated with dermal exposure to volatile organic compounds (VOCs) from feminine hygiene products (FHPs). OBJECTIVES: This study sought to address the gap in understanding the absorption, distribution, metabolism, and excretion dynamics of dermal exposure to VOCs from FHPs and to identify chemicals and products that could cause significant body burden. METHODS: We used measured contents of eight widely present VOCs across five categories of FHPs to estimate dermal exposure, and applied a physiologically based toxicokinetic (PBTK) modeling approach to elucidate VOC toxicokinetics in human body tissues. Inhalation exposure estimates were derived from 20 air samples collected via passive sampling and analyzed using a thermal desorption system coupled with gas chromatography-mass spectrometry. Predicted urinary VOC concentrations based on dermal and inhalation exposure were validated against 99 measurements from 25 females. RESULTS: Via skin absorption, the estimated levels of most target VOCs in nearly all tissues, except adipose and the rest of the body, rapidly peaked within an hour of product use. Specifically, DISCUSSION: These findings reveal potential significant body burden and health risks associated with dermal exposure to VOCs from FHPs, warranting further research and regulatory measures. Comprehensive assessment of internal exposure by integrating with toxicokinetic modeling to elucidate chemical distribution in various tissues is recommended, rather than by measuring only one type of biomarker, to illustrate exposure variances and ensure accurate risk assessment. https://doi.org/10.1289/EHP15418.
2. Gluconic acid alleviates hypertrophic scar formation through binding PLOD1, reducing p-AKT signaling and activating autophagy.
GLA reduced collagen and ACTA2 expression in hypertrophic scar fibroblasts and decreased scar formation and collagen deposition in a rabbit ear model. Mechanistically, GLA binds PLOD1, promotes its autophagy-lysosomal degradation, reduces AKT/p-AKT and mTOR, and activates autophagy; rescue with the AKT agonist SC79 confirmed pathway involvement.
Impact: Reveals a novel anti-scarring mechanism targeting PLOD1 and AKT/mTOR-autophagy, identifying a safe, naturally occurring metabolite as a candidate therapeutic for hypertrophic scars.
Clinical Implications: GLA could be developed into topical or injectable therapies for hypertrophic scars, pending formulation, dermal penetration, dose-ranging, and safety studies; it may complement current standards such as silicone therapy and intralesional corticosteroids.
Key Findings
- GLA suppressed collagen and ACTA2 in hypertrophic scar fibroblasts with minimal effects on proliferation/apoptosis.
- In a rabbit ear model, GLA reduced scar formation and collagen content.
- Mechanistically, GLA reduced AKT and p-AKT, activated autophagy, decreased mTOR, and bound PLOD1 leading to its autophagy-lysosomal degradation; SC79 rescue confirmed AKT pathway involvement.
- GLA did not significantly affect mitochondrial membrane depolarization.
Methodological Strengths
- Comprehensive multi-modal experiments spanning in vitro fibroblast assays and in vivo rabbit scar model.
- Mechanistic validation using docking, pull-down, CETSA, co-localization, and pharmacologic rescue.
Limitations
- Preclinical study without human clinical data; dosing, pharmacokinetics, and toxicity profiles remain unknown.
- Rabbit ear scar model may not fully recapitulate human hypertrophic scar biology.
Future Directions: Develop dermal formulations, assess skin penetration and local/systemic safety, and initiate early-phase clinical trials; explore synergy with established therapies and biomarker-guided patient selection.
BACKGROUND: Hypertrophic scarring represents a major clinical challenge worldwide, with current treatment strategies showing limited effectiveness. Gluconic acid (GLA), a naturally occurring glucose metabolite found in fruits, honey, kombucha tea, and wine, may provide new approach for scar treatment. PURPOSE: This study aimed to investigate the anti-scarring properties of GLA and underlying molecular mechanisms. STUDY DESIGN: A comprehensive experimental study combined in vitro hypertrophic scar fibroblasts and in vivo rabbit ear scar model assays. METHODS: Hypertrophic scar fibroblasts were treated with GLA. Cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate cell viability and apoptosis. The collagen and ACTA2 (actin alpha 2, smooth muscle) expressions were analyzed by qPCR and western blot. A rabbit ear scar model was applied to assess GLA's effects on scar formation and collagen deposition. Transcriptome sequencing, pull-down assays, western blotting and rescue experiments using AKT agonist SC79 were employed to identify GLA-regulated pathways. Molecular docking, pull-down, cellular thermal shift assays and co-localization studies were used to assess GLA's interaction with PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1). E64d, MG132 and QX77 were added to analyze GLA's function mechanisms on PLOD1 protein expression. Autophagy activation was evaluated through autophagic flux assay, transmission electron microscopy and autophagy related protein expression analysis. Mitochondrial membrane potential was detected by JC-1 staining. RESULTS: GLA suppresses collagen and ACTA2 expressions and exerted a mild inhibitory effect on cell proliferation or apoptosis in hypertrophic scar fibroblasts. And it diminishes scar formation and collagen content in the rabbit ear scar model. AKT (protein kinase B) and phosphorylated AKT (p-AKT) levels were significantly reduced after GLA treatment. Rescue experiments confirmed that GLA's effects are mediated through the AKT pathway. Moreover, GLA interacts with PLOD1, resulting in its autophagy-lysosomal degradation. Additionally, GLA treatment activated autophagy, reduced mTOR protein expressions, and had no significant effect on mitochondrial membrane depolarization, further contributing to its anti-scarring effects. CONCLUSION: Our findings demonstrate that GLA attenuates hypertrophic scarring through multi-modal mechanisms involving PLOD1 targeting, AKT/mTOR pathway inhibition, and autophagy activation. This study provides both mechanistic insights and therapeutic potential for GLA in scar treatment.
3. Human and rat ex vivo sweat glands for the observation of acetylcholine induced intracellular calcium signalling.
The authors established a reliable ex vivo calcium-imaging assay for acetylcholine-induced responses in isolated human sweat glands and demonstrated successful cryopreservation with preserved functionality. Rat sweat glands showed similar cholinergic calcium responses, supporting their use to develop and refine methods when human tissues are scarce, thereby facilitating non-animal, human-relevant antiperspirant testing.
Impact: Introduces a scalable, human-relevant ex vivo platform with cryopreservation, enabling mechanistic evaluation of sweat gland function and cosmetic antiperspirants while reducing reliance on animal testing.
Clinical Implications: Provides a translational assay to study disorders of sweating and to screen antiperspirant candidates for efficacy and mechanism, informing dermatologic management of hyperhidrosis and cosmetic product development.
Key Findings
- Established a reliable ex vivo calcium imaging protocol for acetylcholine-induced responses in isolated human sweat glands.
- Demonstrated that human sweat glands can be cryopreserved with preserved viability, structural integrity, and functionality.
- Showed rat sweat glands exhibit similar cholinergic calcium responses to humans, validating their use to develop methods when human samples are scarce.
- The platform enhances analysability and availability of sweat gland samples for cosmetic testing and antiperspirant discovery.
Methodological Strengths
- Direct ex vivo human tissue model with quantitative calcium imaging readouts.
- Cross-species validation and demonstrated cryopreservation preserving function.
Limitations
- Ex vivo responses may not fully recapitulate in vivo neurovascular modulation of sweating.
- Correlation between calcium signals and clinical antiperspirant efficacy remains to be established.
Future Directions: Link calcium responses to sweat output and clinical endpoints, standardize protocols for cosmetic screening, and integrate pharmacologic perturbations to rank antiperspirant mechanisms.
Sweating is imperative for thermoregulatory function in humans. However, many individuals find it undesirable due to its associated malodorous nature. Despite these concerns, aluminium salts remain among the most efficacious sweat-inhibiting agents. Nevertheless, the discovery of novel antiperspirants is challenging due to restrictions on animal testing and the limitations of existing cellular models. Sweat glands, when isolated from human subjects, have been shown to possess only minor functional limitations. Consequently, they are regarded as a leading alternative, despite their limited availability. As the primary analytical metric for isolated sweat glands is sweat output, the objective of this study was to devise experiments that enhance both analysability and availability. We consequently present a method for the reliable observation of intracellular calcium responses in isolated human sweat glands ex vivo. Furthermore, we show that availability can be improved by demonstrating that isolated human sweat glands can be cryopreserved while preserving viability, structural integrity and functionality. In order to obtain these results with limited access to human sweat glands, we set up an experimental set-up using rat sweat glands and compared them to human sweat glands. The study demonstrates that isolated sweat glands from rats and humans exhibit a remarkably similar physiological calcium response to cholinergic stimulation. This validates the use of rat sweat glands as a suitable model for the development of novel experimental procedures, thus circumventing the scarcity of human sweat gland samples. This approach significantly enhanced the analysability and availability of human sweat gland samples. The calcium imaging method applied in this study facilitates the exploration of sweat gland physiology at the cellular level, thereby enabling a more detailed understanding of sweating disorders. This, in turn, enhances the suitability of the model for use in cosmetic testing and the discovery of new antiperspirant agents, thus circumventing the need for animal testing.