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.
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.
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.