PMID- 38483583 OWN - NLM STAT- MEDLINE DCOM- 20240327 LR - 20240330 IS - 1432-0738 (Electronic) IS - 0340-5761 (Print) IS - 0340-5761 (Linking) VI - 98 IP - 5 DP - 2024 May TI - Use of human predictive patch test (HPPT) data for the classification of skin sensitization hazard and potency. PG - 1253-1269 LID - 10.1007/s00204-023-03656-4 [doi] AB - Since the 1940s, patch tests in healthy volunteers (Human Predictive Patch Tests, HPPTs) have been used to identify chemicals that cause skin sensitization in humans. Recently, we reported the results of a major curation effort to support the development of OECD Guideline 497 on Defined Approaches (DAs) for skin sensitization (OECD in Guideline No. 497: Defined Approaches on Skin Sensitisation, 2021a. https://doi.org/10.1787/b92879a4-en ). In the course of this work, we compiled and published a database of 2277 HPPT results for 1366 unique test substances (Strickland et al. in Arch Toxicol 97:2825-2837, 2023. https://doi.org/10.1007/s00204-023-03530-3 ). Here we report a detailed analysis of the value of HPPT data for classification of chemicals as skin sensitizers under the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (GHS). As a result, we propose the dose per skin area (DSA) used for classification by the GHS to be replaced by or complemented with a dose descriptor that may better reflect sensitization incidence [e.g., the DSA causing induction of sensitization in one individual (DSA1+) or the DSA leading to an incidence of induction in 5% of the tested individuals (DSA05)]. We also propose standardized concepts and workflows for assessing individual HPPT results, for integrating multiple HPPT results and for using them in concert with Local Lymph Node Assay (LLNA) data in a weight of evidence (WoE) assessment. Overall, our findings show that HPPT results are often not sufficient for deriving unambiguous classifications on their own. However, where they are, the resulting classifications are reliable and reproducible and can be integrated well with those from other skin sensitization data, such as the LLNA. CI - (c) 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Herzler, Matthias AU - Herzler M AUID- ORCID: 0000-0001-5636-8152 AD - German Federal Institute for Risk Assessment (BfR), Berlin, Germany. matthias.herzler@bfr.bund.de. FAU - Abedini, Jaleh AU - Abedini J AUID- ORCID: 0000-0002-8021-0977 AD - Inotiv, Inc., Morrisville, NC, USA. FAU - Allen, David G AU - Allen DG AUID- ORCID: 0000-0002-8575-9547 AD - Inotiv, Inc., Morrisville, NC, USA. FAU - Germolec, Dori AU - Germolec D AUID- ORCID: 0000-0003-4072-1956 AD - Systems Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Research Triangle Park, NC, USA. FAU - Gordon, John AU - Gordon J AUID- ORCID: 0000-0002-9781-9842 AD - United States Consumer Product Safety Commission, Rockville, MD, USA. FAU - Ko, Hon-Sum AU - Ko HS AUID- ORCID: 0000-0001-9915-7275 AD - United States Food and Drug Administration, Silver Spring, MD, USA. FAU - Matheson, Joanna AU - Matheson J AUID- ORCID: 0000-0002-9912-0322 AD - United States Consumer Product Safety Commission, Rockville, MD, USA. FAU - Reinke, Emily AU - Reinke E AUID- ORCID: 0000-0003-0995-7792 AD - Inotiv, Inc., Morrisville, NC, USA. FAU - Strickland, Judy AU - Strickland J AUID- ORCID: 0000-0002-4112-7484 AD - Inotiv, Inc., Morrisville, NC, USA. FAU - Thierse, Hermann-Josef AU - Thierse HJ AUID- ORCID: 0000-0001-9655-681X AD - German Federal Institute for Risk Assessment (BfR), Berlin, Germany. FAU - To, Kim AU - To K AUID- ORCID: 0000-0001-7973-4602 AD - Inotiv, Inc., Morrisville, NC, USA. FAU - Truax, James AU - Truax J AUID- ORCID: 0000-0002-3550-5602 AD - Inotiv, Inc., Morrisville, NC, USA. FAU - Vanselow, Jens T AU - Vanselow JT AUID- ORCID: 0000-0001-8900-8209 AD - German Federal Institute for Risk Assessment (BfR), Berlin, Germany. FAU - Kleinstreuer, Nicole AU - Kleinstreuer N AUID- ORCID: 0000-0002-7914-3682 AD - National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), Predictive Toxicology Branch, Division of Translational Toxicology, NIEHS/NIH, Research Triangle Park, NC, USA. LA - eng GR - HHSN273201500010C/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Review DEP - 20240314 PL - Germany TA - Arch Toxicol JT - Archives of toxicology JID - 0417615 RN - 0 (Allergens) SB - IM MH - Humans MH - Patch Tests MH - *Dermatitis, Allergic Contact/etiology MH - Allergens/toxicity MH - Skin MH - Local Lymph Node Assay PMC - PMC10965744 OTO - NOTNLM OT - GHS OT - HMT OT - HRIPT OT - Skin sensitization OT - Weight of evidence COIS- The authors declare there exists no conflict of interest. This article may include the work product of employees of the NTP, NIEHS, other governmental agencies or other organizations; however, the statements, opinions, or conclusions contained therein were not approved by, and do not necessarily represent, statements, opinions, or conclusions of the United States or German government, or of any of the organizations to which the authors of this publication are affiliated. Inotiv staff provide technical support for NICEATM, but do not represent NIEHS, NTP, or any U.S. or German agency. EDAT- 2024/03/14 18:42 MHDA- 2024/03/27 06:43 PMCR- 2024/03/14 CRDT- 2024/03/14 12:15 PHST- 2023/11/25 00:00 [received] PHST- 2023/11/30 00:00 [accepted] PHST- 2024/03/27 06:43 [medline] PHST- 2024/03/14 18:42 [pubmed] PHST- 2024/03/14 12:15 [entrez] PHST- 2024/03/14 00:00 [pmc-release] AID - 10.1007/s00204-023-03656-4 [pii] AID - 3656 [pii] AID - 10.1007/s00204-023-03656-4 [doi] PST - ppublish SO - Arch Toxicol. 2024 May;98(5):1253-1269. doi: 10.1007/s00204-023-03656-4. Epub 2024 Mar 14.