Tag Archive for: Skin Sensitization

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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Joint publication with RIFM and IFF: Determining a Point of Departure for Skin Sensitization Potency and Quantitative Risk Assessment of Fragrance Ingredients Using the GARD®skin Dose-Response Assay

Advancing NAMs for Fragrance Safety: Collaborative Research with RIFM and IFF.

As innovators in in vitro skin sensitization testing, addressing key data gaps, we are pleased to share the publication of a new peer-reviewed article in ALTEX, which underscores the performance of GARD®skin Dose-Response in predicting the skin sensitization potency of fragrance ingredients. This study, conducted in collaboration with the expert teams at the Research Institute for Fragrance Materials, Inc. (RIFM) and IFF, contributes valuable insights to the growing body of research supporting more reliable, non-animal testing methods.

The article presents a comprehensive dataset of 100 fragrance ingredients, covering a broad chemical domain with diverse structural reactivity domains and potency levels. The results confirm GARD®skin Dose-Response‘s robust predictivity for skin sensitization potency across this wide chemical spectrum, strengthening its application for deriving No Expected Sensitization Induction Level (NESIL) values in Quantitative Risk Assessment (QRA) within frameworks like Next Generation Risk Assessment (NGRA). These advancements are pivotal in further reducing reliance on animal testing while enhancing risk assessment capabilities.

We would like to extend our gratitude to the exceptional teams who contributed to this collaboration: Isabelle Lee, Andy Forreryd, Mihwa Na, Isabella Schember, Maura Lavelle, Robin Gradin, Ulrika Mattson, Henrik Johansson, Shashi Donthamsetty, Gregory Ladics, and Anne Marie Api.

 

Isabelle Lee, Andy Forreryd, Mihwa Na, Isabella Schember, Maura Lavelle, Robin Gradin, Ulrika Mattson, Henrik Johansson, Shashi Donthamsetty, Gregory Ladics, and Anne Marie Api.
ALTEX - Alternatives to animal experimentation.(2025)
https://www.altex.org/index.php/altex/article/view/2810

Keywords

skin sensitization, fragrance materials, point of departure, OECD TG 442E, GARDskin, new approach methodology


Abstract

Potency and quantitative risk assessment are essential for determining safe concentrations for the formulation of potential skin sensitizers into consumer products. Several new approach methodologies (NAMs) for skin sensitization hazard assessment have been developed, validated, and adopted in OECD test guidelines. However, work is ongoing to develop NAMs for predicting skin sensitization potency on a quantitative scale for use as a point of departure (POD) in next-generation risk assessment (NGRA). GARDskin Dose-Response (DR) is an adaptation of the validated GARDskin assay (OECD TG 442E), and the readout of the assay is a quantitative potency prediction similar to the No Expected Sensitization Induction Level (NESIL) value (µg/cm2). The goal of this study was to evaluate the performance of the GARDskin DR assay for potency prediction of fragrance ingredients. One hundred (100) fragrance ingredients from a reference database covering varied structural reactivity domains and potency were tested in GARDskin DR. Materials tested had varied protein-binding reactivity alerts, including Schiff base, Michael addition, SN2, and acylation. Potency categories were predicted with a total accuracy of 37% and an approximate accuracy (exact match or off by 1 category) of 81%. Combining predicted weak and very weak categories increased total accuracy to 53% and approximate accuracy to 98%. The mean prediction error for the NESIL and local lymph node assay (LLNA) EC3 was 3.15- and 3.36-fold, respectively. Based on the results of this study, GARDskin DR is a promising predictor of skin sensitization potency with an applicability domain covering a wide range of fragrance ingredient reaction mechanisms, increasing the confidence in using the assay to conduct NGRA, ultimately reducing the need for animal testing.

Plain language summary

This study focused on testing a new in vitro method, GARDskin Dose-Response (DR), to predict the quantitative potency of fragrance ingredients in causing skin sensitization. This potency is important for setting safe levels of chemicals in consumer products. The GARDskin DR assay, based on an existing skin sensitization test (OECD TG 442E), provides a quantitative measure of potency similar to the No Expected Sensitization Induction Level (NESIL). One hundred (100) fragrance ingredients with different chemical structures and reactivity patterns were tested. The assay accurately distinguished between sensitizers and non-sensitizers for 81% of the materials, and also correctly predicted their approximate potency categories. The results show that GARDskin DR is a promising tool for predicting quantitative potency for skin sensitization risk, helping to reduce animal testing and support safer product development.

 

Joint publication with L’Oréal: In vitro prediction of skin sensitizing potency using the GARDskin Dose-Response assay: A simple regression approach

New joint publication with L’Oréal.

We are excited to announce the recent publication of a collaborative scientific paper by the expert teams at L’Oréal and SenzaGen, in Toxics MDPI. This peer-reviewed article presents new evidence on the performance of the GARD®skin Dose-Response for quantitative potency assessment of skin sensitizers.

With an extended set of 30 chemicals and a composite potency model for the prediction of sensitizing potency, the study demonstrates the ability of GARD®skin Dose-Response to predict a Point-of-Departure (PoD) for potential skin sensitizers, showing concordance with NESIL values derived from LLNA and Human data.

This research represents a significant advancement in deriving PoD values for chemicals which can be used directly in improving downstream risk assessment strategies.

Gradin R, Tourneix F, Mattson U, Andersson J, Amaral F, Forreryd A, Alépée N, Johansson H. 
Toxics. 2024; 12(9):626. 
https://doi.org/10.3390/toxics12090626

Keywords

NAM; GARDskin Dose-Response; Sensitizing potency; Quantitative risk assessment; Point of departure


Abstract

Toxicological assessments of skin sensitizers have progressed towards a higher reliance on non-animal methods. Current technological trends aim to extend the utility of non-animal methods to accurately characterize skin sensitizer potency.

The GARDskin Dose-Response assay was previously described where it was shown that its main readout, the cDV0 concentration, was associated with skin sensitizing potency. The ability to predict potency in the form of NESILs derived from LLNA or human NOEL, from cDV0, was evaluated. The assessment of a dataset of 30 chemicals showed that the cDV0 values still correlated strongly and significantly with both LLNA EC3 and human NOEL values (ρ = 0.645-0.787 [p < 1×10-3]).

A composite potency value that combined LLNA and human potency data was defined, which aided the performance of the proposed model for the prediction of NESIL. The potency model accurately predicted sensitizing potency, with cross-validation errors of 2.75 and 3.22 fold changes compared with NESILs from LLNA and human, respectively.

In conclusion, the results suggest that the GARDskin Dose-Response assay may be used to derive an accurate quantitative continuous potency estimate of skin sensitizers.

 

Tag Archive for: Skin Sensitization

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