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.

 

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.

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.

 

Joint publication with IFF and RIFM: GARDskin dose-response assay and its application in conducting Quantitative Risk Assessment (QRA) for fragrance materials using a Next Generation Risk Assessment (NGRA) framework

New joint publication with International Flavors & Fragrances Inc (IFF) and Research Institute for Fragrance Materials (RIFM).

SenzaGen scientists, alongside the scientific teams at International Flavors & Fragrances Inc and Research Institute for Fragrance Materials, have jointly published an article in Regulatory Toxicology and Pharmacology, presenting new peer-reviewed evidence on the performance of the GARD®skin Dose-Response assay for Quantitative Risk Assessment of fragrance materials.

The study results confirm the ability of GARD®skin Dose-Response to predict human NESIL values with good predictive performance, showing good concordance with published reference Human data and demonstrating good reproducibility.

Furthermore, the paper also presents a case study to illustrate how the predicted NESIL value from GARDskin Dose-Response can be used in practice within a NGRA framework to establish a maximum allowable concentration of a sensitizer in different consumer products.

The study represents a major step towards the establishment of the assay to derive NESIL values for conducting QRA evaluations for fragrance materials using an NGRA framework.

Shashikiran Donthamsetty, Andy Forreryd, Paul Sterchele, Xiao Huang, Robin Gradin, Henrik Johansson, Ulrika Mattson, Isabelle Lee, Anne Marie Api, Gregory Ladics,
Regulatory Toxicology and Pharmacology, Volume 149, 2024, 105597, ISSN 0273-2300,
https://doi.org/10.1016/j.yrtph.2024.105597

Keywords

QRA (Quantitative Risk Assesment); Dermal sensitization; Fragrance materials; Next Generation Risk Assesment (NGRA); GARD assay; No Expected Sensitization Induction Level (NESIL); New Approach Methodologies (NAMs); OECD 442E

Highlights

  • Developed a Next Generation Risk Assessment (NGRA) framework for conducting QRA2 for fragrance materials.
  • The GARDskin Dose Response (DR) assay is a reliable and reproducible method for predicting NESIL for fragrance materials.
  • NGRA for QRA2 was validated using isocyclocitral as a case study.


Abstract

Development of New Approach Methodologies (NAMs) capable of providing a No Expected Sensitization Induction Level (NESIL) value remains a high priority for the fragrance industry for conducting a Quantitative Risk Assesment (QRA) to evaluate dermal sensitization. The in vitro GARDskin assay was recently adopted by the OECD (TG 442E) for the hazard identification of skin sensitizers. Continuous potency predictions are derived using a modified protocol that incorporates dose-response measurements. Linear regression models have been developed to predict human NESIL values. The aim of the study was to evaluate the precision and reproducibility of the continuous potency predictions from the GARDskin Dose-Response (DR) assay and its application in conducting QRA for fragrance materials using a Next Generation Risk Assessment (NGRA) framework. Results indicated that the GARDskin Dose-Response model predicted human NESIL values with a good degree of concordance with published NESIL values, which were also reproducible in 3 separate experiments. Using Isocyclocitral as an example, a QRA was conducted to determine its safe use levels in different consumer product types using a NGRA framework. This study represents a major step towards the establishment of the assay to derive NESIL values for conducting QRA evaluations for fragrance materials using a NGRA framework.

Evaluation of the applicability of GARDskin to predict skin sensitizers in extracts from medical device materials

Peer-reviewed article in Frontiers in Toxicology.

The application of GARD®skin to predict potential skin sensitizers in extracts from Medical Device materials has recently been published in a peer-reviewed article in Frontiers in Toxicology.

The study results provide evidence recognizing the GARD®skin Medical Device assay as a scientifically sound and ethical alternative to conventional animal methods, compatible with both polar and non-polar extraction vehicles, in line with the ISO 10993-12:2021 standard.

We are proud to provide the only OECD-validated in vitro assay for sensitization that is fully compatible with testing requirements specified in ISO 10993-12.

Jenvert Rose-Marie, Larne Olivia, Johansson Angelica, Berglin Mattias, Pedersen Emma, Johansson Henrik
Frontiers in Toxicology, Volume 6, 2024,ISSN 2673-3080
DOI=10.3389/ftox.2024.1320367

Keywords

GARD™; In vitro; Skin sensitisation; NAMs; Medical Device, ISO 10993, Biocompatibility

Abstract

Biocompatibility testing of medical devices is governed by the ISO 10993 series of standards and includes evaluation of skin sensitization potential of the final product. A majority of all medical devices are tested using in vivo methods, largely due to the lack of in vitro methods validated within the applicability domain of solid materials. The GARDskin method for assessment of chemical skin sensitizers is a validated method included in the OECD Test Guideline 442E, based on evaluation of transcriptional patterns of an endpoint-specific genomic biomarker signature in a dendritic cell-like cell, following test chemical exposure. The current study aimed to evaluate the applicability of GARDskin for the purpose of testing solid materials by incorporation of extraction procedures described in ISO 10993-12:2021, as well as to demonstrate the functionality of the proposed protocols, by testing of custom-made materials spiked with sensitizing agents. It was shown that GARDskin is compatible with both polar and non-polar extraction vehicles frequently used for the purpose of medical device biological testing. Further, exploring three different material types spiked with up to four different sensitizing agents, as well as three unspiked control materials and commercial reference products, it was shown that the method correctly classified all evaluated test materials. Taken together, the data presented suggest that GARDskin may constitute a valid alternative to in vivo experimentation for the purpose of skin sensitization assessment of medical devices.

 

Joint publication with Corteva Agriscience: GARD™skin and GARD™potency: A proof-of-concept study investigating applicability domain for agrochemical formulations

New joint publication with Corteva Agriscience.

SenzaGen scientists, alongside the toxicology team at Corteva Agriscience, have recently published a joint study in Regulatory Toxicology and Pharmacology, presenting new peer-reviewed evidence on the applicability of GARD® for agrochemical formulations.

The study demonstrates a satisfactory performance of GARD®skin and GARD®potency for skin sensitization hazard and GHS potency categorization of tested agrochemical formulations.

Marco Corvaro, Joseph Henriquez, Raja Settivari, Ulrika Mattson, Andy Forreryd, Robin Gradin, Henrik Johansson, Sean Gehen,
Regulatory Toxicology and Pharmacology, Volume 148, 2024, 105595, ISSN 0273-2300,
https://doi.org/10.1016/j.yrtph.2024.105595.

Keywords

GARD™; In vitro; Skin sensitisation; NAMs; Agrochemical formulations

Highlights

  • Tested 42 agrochemical formulations to expand applicability domain of GARD.

  • GARDskin showed good accuracy (76.2%), sensitivity (85.0%) and specificity (68.2%).
  • GARDpotency correctly subcategorized 14/17, correctly predicted sensitisers.
  • GARD satisfactory for Key Event 3 characterisation of agrochemical formulations.


Abstract

Several New Approach Methodologies (NAMs) for hazard assessment of skin sensitisers have been formally validated. However, data regarding their applicability on certain product classes are limited. The purpose of this project was to provide initial evidence on the applicability domain of GARD™skin and GARD™potency for the product class of agrochemical formulations.

For this proof of concept, 30 liquid and 12 solid agrochemical formulations were tested in GARDskin for hazard predictions. Formulations predicted as sensitisers were further evaluated in the GARDpotency assay to determine GHS skin sensitisation category. The selected formulations were of product types, efficacy groups and sensitisation hazard classes representative of the industry’s products.

The performance of GARDskin was estimated by comparing results to existing in vivo animal data. The overall accuracy, sensitivity, and specificity were 76.2% (32/42), 85.0% (17/20), and 68.2% (15/22), respectively, with the predictivity for liquid formulations being slightly higher compared to the solid formulations. GARDpotency correctly subcategorized 14 out of the 17 correctly predicted sensitisers. Lack of concordance was justifiable by compositional or borderline response analysis. In conclusion, GARDskin and GARDpotency showed satisfactory performance in this initial proof-of-concept study, which supports consideration of agrochemical formulations being within the applicability domain of the test methods.

 

New scientific publication by ExxonMobil: Challenges integrating skin sensitization data for assessment of difficult to test substances

New scientific publication by ExxonMobil.

Check out this newly published article by ExxonMobil focusing on the challenges of determining skin sensitization hazard in the case of difficult-to-test substances with conflicting or low-confidence data, where GARDskin data on UVCBs and hydrophobic substances provides valuable input for the integrated hazard assessment.

The article provides new peer-reviewed evidence for the applicability domain of GARDskin on UVCBs, hydrophobic and highly complex substances.

Greminger A, Frasca J, Goyak K, North C. 
Challenges integrating skin sensitization data for assessment of difficult to test substances. 
ALTEX - Alternatives to animal experimentation, published Oct 12, 2023
doi: 10.14573/altex.2201122. Epub ahead of print. PMID: 37843019.

Keywords

LLNA; ToxPi; new approach methodologies; skin sensitization; weight of evidence.


Abstract

Difficult to test substances including poorly soluble, mildly irritating, or Unknown or Variable Composition Complex reaction products or Biological Materials (UVCBs), producing weak or borderline in vivo results, face additional challenges in in vitro assays that often necessitates data integration in a weight of evidence (WOE) approach to inform skin sensitization potential. Here we present several case studies on difficult to test substances and highlight the utility of Toxicological Prioritization Index (ToxPi) as a data visualization tool to compare skin sensitization biological activity. The case study test substances represent two poorly soluble substances, tetrakis (2-ethylbutyl) orthosilicate and decyl palmitate, and two UVCB substances, alkylated anisole and hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2 undecanone. Data from key events within the skin sensitization adverse outcome pathway were gathered from publicly available sources or specifically generated. Incorporating the data for these case study test substances as well as on chemicals of a known sensitization class (sensitizer, irritating non-sensitizer, and non-sensitizer) into ToxPi produced biological activity profiles which were grouped using unsupervised hierarchical clustering. Three of the case study test substances concluded to lack skin sensitization potential by traditional WOE produced biological activity profiles most consistent with non-sensitizing substances, whereas the prediction was less definitive for a substance considered positive by traditional WOE. Visualizing the data using bioactivity profiles can provide further support for WOE conclusions in certain circumstances but is unlikely to replace WOE as a stand-alone prediction due to limitations of the method including the impact of missing data points.