Here you can find essential publications underpinning IDEA's work.
Reference Chemical Potency List (RCPL): A new tool for evaluating the accuracy of skin sensitisation potency measurements by New Approach Methodologies (NAMs)
Considerable progress has been made in the design of New Approach Methodologies (NAMs) for the hazard identification of skin sensitising chemicals. However, effective risk assessment requires accurate measurement of sensitising potency, and this has proven more difficult to achieve without recourse to animal tests.
One important requirement for the development and adoption of novel approaches for this purpose is the
availability of reliable databases for determining the accuracy with which sensitising potency can be predicted. Some previous approaches have relied on comparisons with potency estimates based on either human or animal (local lymph node assay) data. In contrast, we here describe the development of a carefully curated Reference Chemical Potency List (RCPL) which is based on consideration of the best available human and animal data.
The RCPL is comprised of 33 readily available chemicals that span a wide range of chemistry and sensitising potency, and contain examples of both direct and indirect (pre- and pro-) haptens. For each chemical a potency value (PV) was derived, and chemicals ranked according to PV without the use of potency categories. It is proposed that the RCPL provides an effective resource for assessment of the accuracy with which NAMs can measure skin sensitising potency.
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Updating exposure assessment for skin sensitization quantitative risk assessment for fragrance materials
In 2008, a proposal for assessing the risk of induction of skin sensitization to fragrance materials Quantitative Risk Assessment 1 (QRA1) was published. This was implemented for setting maximum limits for fragrance materials in consumer products. However, there was no formal validation or empirical verification after implementation. Additionally, concerns remained that QRA1 did not incorporate aggregate exposure from multiple product use and included assumptions, e.g. safety assessment factors (SAFs), that had not been critically reviewed.
Accordingly, a review was undertaken, including detailed re-evaluation of each SAF together with development of an approach for estimating aggregate exposure of the skin to a potential fragrance allergen. This revision of QRA1, termed QRA2, provides an improved method for establishing safe levels for sensitizing fragrance materials in multiple products to limit the risk of induction of contact allergy. The use of alternative non-animal methods is not within the scope of this paper.
Ultimately, only longitudinal clinical studies can verify the utility of QRA2 as a tool for the prevention of contact allergy to fragrance materials.
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An extended Reference Chemical Potency List (RCPL) for characterising the performance of New Approach Methodologies (NAMs) in measuring the skin sensitisation potency of fragrance chemicals
Highlights
The development of a Reference Chemical Potency List (RCPL), and its purpose, has been described previously. That original RCPL comprised 33 chemicals, of varying skin sensitising activity, for each of which a discrete Potency Value (PV) was derived, based upon the best available human and/or animal (local lymph node assay) data. The purpose of the RCPL was to provide a reliable tool that would facilitate evaluation of the ability of New Approach Methodologies (NAMs) to measure skin sensitising potency. We here report the construction of an extended RCPL with 77 additional chemicals by applying the weight of evidence framework used previously. This extended RCPL adheres to the salient features of the original database. These comprise a focus largely on fragrance chemicals, provision of a wide range of chemical structures and of skin sensitising potency, the inclusion of both direct and indirect (pre- and pro-) haptens, the exclusion of NAMs data for the derivation of PVs, and avoidance of the use of potency categories for the classification of chemicals. It is anticipated that this extended RCPL will provide a more powerful database with which to assess the strengths and weakness of recently developed NAMs in the measurement of skin sensitising potency.
Link: https://www.sciencedirect.com/science/article/pii/S027323002500176X
Derivation of a Point of Departure using NAMs for application in Quantitative Risk Assessment of fragrance materials
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.
https://www.sciencedirect.com/science/article/pii/S0273230026000255
Extended fragrance ingredients surveillance study (EFISS)—protocol for a clinical surveillance study on contact allergy to 7 fragrance materials in widespread use but hitherto not systematically patch tested
Contact allergy (CA) is not uncommon in the population, including to various fragrance allergens. If not diagnosed correctly, allergic contact dermatitis (ACD) may ensue, because targeted allergen avoidance is not possible.
The primary objective of the study is to estimate the prevalence of CA to seven fragrance materials in patients with suspected ACD across Europe. Based on the outcome, a conclusion will be drawn as to whether present risk management regarding maximum recommended concentrations of each of these, based on quantitative risk assessment (QRA2), is adequate. The planned study is a surveillance study based on consecutive patients, patch tested in 10 European departments of dermatology with a series of allergens as indicated by their personal history, including the European baseline series, supplemented with the seven additional fragrance ingredients. The patch test procedure will follow the guideline of the European Society of Contact Dermatitis (ESCD) with additional standardization procedures.
The envisaged sample size is 8100; recruitment will be in three data cycles with brief intervals allowing for descriptive interim analyses. Those patients reacting positively to any of the study allergens will be followed-up specifically to identify the source of sensitizing and/or eliciting exposure(s). Results will inform risk reassessment and subsequent risk management measures. Study results will be published in an open-access peer-reviewed scientific journal. Structured post-marketing surveillance of consumer risk of contact allergy by monitoring prevalences of positive patch test reactions in a dedicated European expert network is developed which can serve as a model for further chemicals.
Important outcomes will be either a confirmation of effectiveness of risk management measures in place, or alternatively identifying aspects needing improvement (for certain cosmetic product categories). DRKS registration (DRKS00033263) 16.09.2024, mirrored at https://trialsearch.who.int
Link: https://link.springer.com/article/10.1007/s00403-025-04286-9