Joint poster with RIFM and IFF: In vitro Skin Sensitization Potency Prediction Performance on the RCPL list

GARD®skin Dose-Response for skin sensitizing potency assessment: Performance on the Reference Chemical Potency List (RCPL)


Presented at BTS 2024.

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Conclusion

  • This study suggests that GARDskin Dose-Response is a potent predictor of skin sensitizing potency on a continuous scale.
  • Predicted potency values are in µg/cm2 and can be used for risk assessment and to establish a maximum allowable concentration of a sensitizer in various consumer products.

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Abstract

New Approach methods (NAMs) for assessment of skin sensitizing hazard and GHS potency have been adopted as OECD Test Guidelines. However, NAMs able to estimate skin sensitization potency on a continous scale, and thereby generating data for use as a point of departure (PoD) in next-generation risk assessment (NGRA) strategies, are currently lacking.

GARDskin Dose-Response (DR) is based on the validated protocols of GARDskin (OECD TG 442E). The readout of the assay is a continous potency prediction, or a No Expected Sensitization Induction Level (NESIL) value (ug/cm2).

The aim of this study was to evaluate the performance of the potency predictions from GARDskin DR using the chemicals in the Reference Chemical Potency List (RCPL) as a reference. The RCPL contains curated Potency Values (PVs) and was developed to serve as a resource for evaluating potency predictions from NAM-based approaches.

GARDskin data was generated (n=27 chemicals) and potency predictions were compared to PV values from the RCPL list. The continous potency predictions from GARDskin DR correlated well with PVs (p: 0.74), with an average misprediction of 3.7-fold from reference values. Furthermore, GARDskin DR provided a very similar potency ranking compared to the ranking based on PV values in the RCPL list (ρ: 0.69).

In conclusion, based on the results in this study, GARDskin DR was demonstrated to be a potent predictor of skin sensitizing potency, increasing the confidence in using the assay to conduct NGRA on new chemical entities, ultimately reducing the need for confirmatory human and/or animal studies.

Keywords: NAM, GARDskin Dose-Response, Sensitizing potency, Quantitative risk assessment, Point of departure