The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitization
Mechanistically based non-animal methods for assessing skin sensitization hazard have been developed, but are not considered sufficient, individually, to conclusively define the skin sensitization potential or potency of a chemical. This resulted in the development of defined approaches (DAs), as do...
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Elsevier
2025-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X24000586 |
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| author | Emily N. Reinke Joe Reynolds Nicola Gilmour Georgia Reynolds Judy Strickland Dori Germolec David G. Allen Gavin Maxwell Nicole C. Kleinstreuer |
| author_facet | Emily N. Reinke Joe Reynolds Nicola Gilmour Georgia Reynolds Judy Strickland Dori Germolec David G. Allen Gavin Maxwell Nicole C. Kleinstreuer |
| author_sort | Emily N. Reinke |
| collection | DOAJ |
| description | Mechanistically based non-animal methods for assessing skin sensitization hazard have been developed, but are not considered sufficient, individually, to conclusively define the skin sensitization potential or potency of a chemical. This resulted in the development of defined approaches (DAs), as documented in OECD TG 497, for combining information sources in a prescriptive manner to provide a determination of risk or potency. However, there are currently no DAs within OECD TG 497 that can derive a point of departure (POD) for risk assessment. The Skin Allergy Risk Assessment – Integrated Chemical Environment (SARA-ICE) DA for skin sensitization is a Bayesian statistical model that estimates a human-relevant metric of sensitizer potency, the ED01, an estimate of the human predictive patch test dermal dose at which there is 1% chance of inducing sensitization, which can be used in a risk assessment paradigm. The model accounts for variability of input data and explicitly quantifies uncertainty. SARA-ICE derives the ED01 from a variety of in vitro and in vivo test method data and is built upon historical human, murine, and in vitro test data for 434 chemicals. In addition to the ED01 POD SARA-ICE DA also provides a Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classification probability for GHS subcategories 1A, 1B and not classified (NC). Here we describe the SARA-ICE model and its evaluation, including performance versus benchmark PODs. In addition, via a case study with isothiazolinones (ITs), we demonstrate the utility of SARA-ICE for integrating different data inputs and compare the ED01 for six ITs to existing historical data. |
| format | Article |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Current Research in Toxicology |
| spelling | doaj-art-3fb7d79eee2d4b0da7cd5b1c2c4c7f882025-08-20T02:03:14ZengElsevierCurrent Research in Toxicology2666-027X2025-01-01810020510.1016/j.crtox.2024.100205The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitizationEmily N. Reinke0Joe Reynolds1Nicola Gilmour2Georgia Reynolds3Judy Strickland4Dori Germolec5David G. Allen6Gavin Maxwell7Nicole C. Kleinstreuer8Inotiv, Inc., Morrisville, NC 27560, USA; Corresponding authors at: Emily Reinke, Inotiv, Inc., 601 Keystone Park Drive, Suite 200, Morrisville, NC 27650, USA.Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedforshire MK44 1LQ, United KingdomUnilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedforshire MK44 1LQ, United KingdomUnilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedforshire MK44 1LQ, United KingdomInotiv, Inc., Morrisville, NC 27560, USANational Institute of Environmental Health Sciences, Division of Translational Toxicology, National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, P.O. Box 12233, Research Triangle Park, NC 27709, USAInotiv, Inc., Morrisville, NC 27560, USAUnilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedforshire MK44 1LQ, United KingdomNational Institute of Environmental Health Sciences, Division of Translational Toxicology, National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, P.O. Box 12233, Research Triangle Park, NC 27709, USAMechanistically based non-animal methods for assessing skin sensitization hazard have been developed, but are not considered sufficient, individually, to conclusively define the skin sensitization potential or potency of a chemical. This resulted in the development of defined approaches (DAs), as documented in OECD TG 497, for combining information sources in a prescriptive manner to provide a determination of risk or potency. However, there are currently no DAs within OECD TG 497 that can derive a point of departure (POD) for risk assessment. The Skin Allergy Risk Assessment – Integrated Chemical Environment (SARA-ICE) DA for skin sensitization is a Bayesian statistical model that estimates a human-relevant metric of sensitizer potency, the ED01, an estimate of the human predictive patch test dermal dose at which there is 1% chance of inducing sensitization, which can be used in a risk assessment paradigm. The model accounts for variability of input data and explicitly quantifies uncertainty. SARA-ICE derives the ED01 from a variety of in vitro and in vivo test method data and is built upon historical human, murine, and in vitro test data for 434 chemicals. In addition to the ED01 POD SARA-ICE DA also provides a Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classification probability for GHS subcategories 1A, 1B and not classified (NC). Here we describe the SARA-ICE model and its evaluation, including performance versus benchmark PODs. In addition, via a case study with isothiazolinones (ITs), we demonstrate the utility of SARA-ICE for integrating different data inputs and compare the ED01 for six ITs to existing historical data.http://www.sciencedirect.com/science/article/pii/S2666027X24000586Skin sensitizationNon-animal methodologyRisk assessmentLLNAPoint of departureBayesian |
| spellingShingle | Emily N. Reinke Joe Reynolds Nicola Gilmour Georgia Reynolds Judy Strickland Dori Germolec David G. Allen Gavin Maxwell Nicole C. Kleinstreuer The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitization Current Research in Toxicology Skin sensitization Non-animal methodology Risk assessment LLNA Point of departure Bayesian |
| title | The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitization |
| title_full | The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitization |
| title_fullStr | The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitization |
| title_full_unstemmed | The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitization |
| title_short | The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitization |
| title_sort | skin allergy risk assessment integrated chemical environment sara ice defined approach to derive points of departure for skin sensitization |
| topic | Skin sensitization Non-animal methodology Risk assessment LLNA Point of departure Bayesian |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X24000586 |
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