Tag Archive for: Skin Sensitization

Joint article: Skin sensitization assessment for wearable devices



Advancing skin sensitization assessment for wearable devices

Assessing the Skin Sensitizing Potential of Constituents and Leachables from Wearable Devices Using GARDskin and Associated Applications

A new joint article has been published in Toxics, providing new peer-reviewed evidence demonstrating how the GARD® assays can support both quantitative risk assessment of wearable device constituents and hazard identification of leachables from finished products.

As wearable technologies continue to evolve, safety assessment presents unique challenges. Materials are often complex, multi-component, and intended for prolonged skin contact. This study highlights how New Approach Methodologies (NAMs) can generate the information needed for both product development and final product safety evaluations.

About the study

The study explores two complementary non-animal testing applications:

Part 1: Quantitative potency assessment of wearable device constituents
Six representative chemicals commonly used in wearable devices, including three acrylate monomers, two acrylamide monomers, and one reactive dye, were evaluated using GARD®skin Dose-Response to determine skin sensitization potency and derive Points of Departure (PoDs) for quantitative risk assessment.

Part 2: Hazard identification of leachables from finished products
In a proof-of-concept case study, GARD®skin Medical Device was used to evaluate extracts of MED-2000 prepared in both polar and non-polar extraction vehicles and spiked with the known sensitizer isobornyl acrylate (IBOA).

Key findings:

  • All six wearable-relevant test chemicals were correctly identified as skin sensitizers, demonstrating strong performance within this applicability domain.
  • GARD®skin Dose-Response generated quantitative potency estimates that were in line with available in vivo reference data and showed good concordance with potency values generated using defined approaches.
  • GARD®skin Medical Device successfully detected IBOA in both polar and non-polar material extracts, supporting its applicability for testing leachables from solid materials and wearable devices.

Together, these findings demonstrate how GARD®-based testing strategies can support both safer-by-design product development and the biological safety assessment of final wearable devices, while reducing reliance on animal testing.

Authors

We extend our sincere gratitude to the outstanding team members who contributed to this scientific collaboration: Ravi Persaud1, Andy Forreryd2, Robin Gradin2, Emma Anders2, Johan Andersson2, Per Alftrén2, Henrik Johansson2 and, Nakul Ruparel1

1Apple, Inc., Cupertino, CA 95014, USA
2SenzaGen AB, SE-22481 Lund, Sweden

Keywords

wearable devices; skin sensitization; GARD; quantitative potency assessment


Abstract

Pre-clinical toxicological evaluation is an essential component of ensuring the safety and compatibility of wearable devices with biological systems. Along with the local endpoints of cytotoxicity and irritation, skin sensitization is a core toxicological endpoint. Testing wearable devices, which are often solid and composed of multiple components, presents new challenges for New Approach Methods. In the current proof-of-concept study, we propose a strategy for conducting risk assessment of the individual components and the leachables from wearable devices.

The GARDskin Dose-Response assay (OECD TGP 4.106) was used to predict the skin sensitization potency of three acrylate monomers, two acrylamide monomers, and one reactive dye. The GARDskin Medical Device (ISO 10993-10:2021, Annex C) was used to classify MED-2000 extracts spiked with isobornyl acrylate. All chemicals were classified as skin sensitizers. The quantitative potency predictions correlated well with available data from defined approaches and produced near-identical potency rankings.

Available human and animal reference data were too sparse and heterogenous to substantiate agreement in potency. Finally, the GARDskin Medical Device assay correctly classified the spiked extract as skin sensitizing. In conclusion, the GARDskin assay and associated applications are well adapted to address the testing requirements for wearable devices.

 

Joint publication with dōTERRA: Skin Sensitization potency assessment of Essential Oils



Advancing Skin Sensitization potency assessment for Essential Oils

Comparative analysis of a component-based prediction model, GARDskin Dose-Response assay, and the Local Lymph Node Assay (LLNA)

A new joint article by researchers from dōTERRA and SenzaGen has been published in Toxics, providing new peer-reviewed evidence supporting the applicability of GARD®skin Dose-Response for quantitative skin sensitization potency assessment of Essential Oils, a representative class of Natural Complex Substances (NCS).

The study addresses a key gap in non-animal skin sensitization testing: the quantitative potency assessment of complex mixtures. Results demonstrate strong overall concordance between GARD®skin Dose-Response and historical LLNA data, supporting the use of New Approach Methodologies (NAMs) to derive Points of Departure (PoDs) for quantitative skin sensitization risk assessment of complex mixtures.

About the study

Eight well-studied Essential Oils were evaluated using two non-animal approaches and benchmarked against historical LLNA data:

  • GARD®skin Dose-Response: a genomics-based assay that extends the standard GARDskin OECD 442E methodology to enable quantitative skin sensitization potency assessment.
  • Component-based Prediction (CP) model: a computational approach using constituent composition and known sensitization potency data to estimate mixture potency.

Key findings:

  • Confirmed applicability of GARD®skin Dose-Response to Essential Oils for quantitative potency assessment.
  • Strong overall concordance across all three approaches, indicating comparable potency estimates.
  • GARD®-derived potency values generally aligned with historical LLNA data, supporting the method’s relevance for skin sensitization risk assessment.

Together, these findings provide further evidence supporting the use of non-animal approaches for quantitative skin sensitization risk assessment of complex mixtures. 

Dawson, Joseph T., Tim Lindberg, Prabodh Satyal, Ambika Poudel, Dakota T. Carter, Sara A. Shah, and Cécile Bascoul. 2026. 
"Comparative Analysis of Test Methods for Predicting Dermal Sensitization Potency in Essential Oils: A Component-Based Prediction Model, GARDskin Dose–Response Assay, and Local Lymph Node Assay"
Toxics 14, no. 9: 800. https://doi.org/10.3390/toxics14090800

Keywords

Skin sensitization; risk assessment; essential oils; mixtures; non-animal methods; new approach methodologies (NAMs); component-based prediction; GARDskin Dose-Response; local lymph node assay; comparative analysis


Abstract

The dose–response adaptation of the genomic allergen rapid detection for skin sensitizers (GARDskin DR) assay is a non-animal method for predicting sensitization potency. This proof-of-concept comparative analysis evaluates outputs from a component-based prediction model (CP), GARDskin DR, and historical local lymph node assays (LLNA), exploring the applicability of CP and GARDskin DR for evaluating the no-expected-sensitization induction level (NESIL) potencies of essential oils.

Eight well-studied essential oils were selected: cedarwood, cinnamon bark, clove bud, geranium, lavender, lemongrass, spearmint, and tea tree oils. Each underwent GARDskin DR as well as GC–MS, from which CP model outputs were derived. GARDskin DR, CP, and LLNA outputs were compared graphically and using preliminary descriptive statistics.

Results show overall statistical concordance in material ranking between methods (Kendall’s W = 0.857, p = 0.017). Bland–Altman log-transformed bias and limits of agreement show numerically higher NESILCP compared to corresponding NESILGARD and NESILLLNA, but sensitivity analysis shows this finding is statistically sensitive to geranium oil. Spearman’s rank correlations were significant between NESILCP vs. NESILGARD and NESILLLNA but not between NESILGARD vs. NESILLLNA despite numerical similarity.

Given the small sample, no statistical findings from this study are generalizable and should be interpreted descriptively. However, the NESIL results provide preliminary evidence supporting further evaluation of GARDskin DR and CP for dermal sensitization potency testing of essential oils.

 

New peer-reviewed publication by IDEA working group: Derivation of a Point of Departure using NAMs for application in Quantitative Risk Assessment of fragrance material

Advancing quantitative NAMs for skin sensitization risk assessment – Collaborative work within IDEA QRA-NAMs Working Group

A new article published in Regulatory Toxicology and Pharmacology presents the outcomes of collaborative work within the International Dialogue for the Evaluation of Allergens (IDEA) QRA-NAMs Working Group.

The publication demonstrates how quantitative New Approach Methodologies (NAMs) can be used to derive Points of Departure (PoDs) for skin sensitization risk assessment.

The study provides peer-reviewed evidence that SenzaGen’s single-assay method GARD®skin Dose-Response, alongside the multiple-assay approaches, delivers PoDs that well align with established human and animal reference potency data, within the expected biological variability.

We are proud that SenzaGen expert Dr Andy Forreryd contributed to the scientific discussions and to the development of the GARD®skin dose-response methodology supporting this work.

About the study

Three quantitative NAM approaches were evaluated across 110 fragrance-related chemicals, benchmarked against the extended IDEA Reference Chemical Potency List (RCPL), which integrates human and animal reference data:
  • Defined approaches combining multiple assays: Regression model and SARA-ICE.
  • GARD®skin Dose-Response: a genomic-based assay evaluated as a stand-alone method.

Scientific and regulatory impact

The work addresses a critical gap in NAM adoption: moving beyond hazard identification to quantitative, decision-relevant risk assessment.

Importantly, the study goes further than method comparison by defining NAM-specific adjustment factors, enabling translation of NAM-PoDs into NESILs for use in Quantitative Risk Assessment (QRA), even for new materials where no legacy data are available. Together, these results provide a scientifically robust and practically applicable framework for implementing quantitative, NAM-based skin sensitization risk assessment and support the continued transition toward animal-free, human-relevant safety assessment.

 

ndreas Natsch, Peter Griem, Amaia Irizar, James Bridges, Matthias Vey, Isabelle Lee, Anne Marie Api, Petra Kern, Ian Kimber,
Derivation of a Point of Departure using NAMs for application in Quantitative Risk Assessment of fragrance materials,
Regulatory Toxicology and Pharmacology,
Volume 167,2026,106052,ISSN 0273-2300,https://doi.org/10.1016/j.yrtph.2026.106052.
https://www.sciencedirect.com/science/article/pii/S0273230026000255

Keywords

Skin sensitization, In vitro testing, Point of departure, Quantitative risk assessment, SARA-ICE, Regression model, GARDskin


Abstract

Skin sensitization is a key endpoint for the safety assessment of topical consumer products. Ingredients with the potential to act as skin sensitizers differ markedly in their threshold for induction but can be used safely if their potency is characterized and exposure remains within an appropriate margin of safety. To this end, the fragrance industry co-developed Quantitative Risk Assessment (QRA) which starts with the No-Expected-Sensitization-Induction-Level (NESIL). Historically, QRA relies on a weight of evidence approach based on animal data, human confirmatory tests and read across. To allow an approach based solely on New Approach Methodologies (NAMs), the International Dialogue for the Evaluation of Allergens (IDEA) initiative, developed an extended Reference Chemical Potency List (RCPL) integrating human and animal data to derive potency values (PV). Here, we use PVs to evaluate the suitability of quantitative NAMs, including Defined Approaches (DAs), to derive a Point-of-Departure (NAM-PoD) for skin sensitization potency assessment. Evaluation of NAM-PoD derived by SARA-ICE DA, Regression DA and GARDskin dose-response assay (GSDR), indicates that the sensitization potency of fragrance chemicals can be reliably predicted using each approach. Through comparison of NAM-PoDs with in vivo human sensitization thresholds, NAM-specific adjustment factors were derived to convert NAM-PoDs into NAM-NESILs for QRA.

 

In Vitro Skin Sensitization Testing of Medical Devices

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Biocompatibility Testing of Medical Devices

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Published report by NICEATM: Evaluation of the GARDskin Sensitization Test Method Using Substances of Regulatory Interest

NICEATM’s report confirms the inclusion of GARDskin improved the overall performance of the Defined Approaches for Skin Sensitization (DASS)

The recent published report by NICEATM* summarizes an evaluation of the performance of the GARD®skin assay for predicting skin sensitization hazard and potency for chemicals nominated by ICCVAM member agencies.

The evaluation compared the results of the GARDskin assay alone and in applicable defined approaches for identifying skin sensitizers with reference results derived from the murine local lymph node assay, human skin sensitization reference data, and three other non-animal skin sensitization test methods.

Overall, the GARDskin assay performed well against the other assays for predicting skin sensitization hazard and potency classifications. Performance statistics for the defined approaches that included the GARDskin assay suggested that its addition improved those defined approaches.

Full report

 

*NICEATM (National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods) is a U.S. government center that promotes the development, validation, and adoption of alternative test methods that reduce, refine, or replace animal use in toxicology. NICEATM evaluates new in vitro, computational, and integrated approaches for regulatory safety testing and coordinates with agencies like ICCVAM to support their regulatory acceptance.

Skin Sensitization Potency Assessment

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A Quick Guide to Skin Sensitization Testing

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Tag Archive for: Skin Sensitization

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