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. 2021 Oct:125:105026.
doi: 10.1016/j.yrtph.2021.105026. Epub 2021 Aug 10.

Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients

M P Dent  1 , E Vaillancourt  2 , R S Thomas  3 , P L Carmichael  4 , G Ouedraogo  5 , H Kojima  6 , J Barroso  7 , J Ansell  8 , T S Barton-Maclaren  9 , S H Bennekou  10 , K Boekelheide  11 , J Ezendam  12 , J Field  13 , S Fitzpatrick  14 , M Hatao  15 , R Kreiling  16 , M Lorencini  17 , C Mahony  18 , B Montemayor  19 , R Mazaro-Costa  20 , J Oliveira  21 , V Rogiers  22 , D Smegal  23 , R Taalman  24 , Y Tokura  25 , R Verma  26 , C Willett  27 , C Yang  28
Affiliations

Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients

M P Dent et al. Regul Toxicol Pharmacol. 2021 Oct.

Abstract

Next generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort is needed to develop and test the in vitro and in silico (computational) approaches that underpin NGRA to enable confident application in a regulatory context. A workshop was held in Montreal in 2019 to discuss where effort needs to be focussed and to agree on the steps needed to ensure safety decisions made on cosmetic ingredients are robust and protective. Workshop participants explored whether NGRA for cosmetic ingredients can be protective of human health, and reviewed examples of NGRA for cosmetic ingredients. From the limited examples available, it is clear that NGRA is still in its infancy, and further case studies are needed to determine whether safety decisions are sufficiently protective and not overly conservative. Seven areas were identified to help progress application of NGRA, including further investments in case studies that elaborate on scenarios frequently encountered by industry and regulators, including those where a 'high risk' conclusion would be expected. These will provide confidence that the tools and approaches can reliably discern differing levels of risk. Furthermore, frameworks to guide performance and reporting should be developed.

Keywords: In silico; In vitro; Next generation risk assessment; Non-animal approaches.

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Figures

Fig. 1.
Fig. 1.
The 9 ICCR principles of next generation risk assessment (NGRA) of cosmetic ingredients (Dent et al., 2018).
Fig. 2.
Fig. 2.
Points of departure (PoDs) plotted against predicted plasma exposure for coumarin case study (face cream exposure). PoDs expressed as free concentration in assay/plasma. Red line = Plasma Cmax free (μM); pink band = uncertainty band in plasma level prediction. 1 = IL1β+TNFα+IFNγ; 2 = IL1β+TNFα+IFNγ+TGFβ. BERs calculated to be between 2500 and 38000.
Fig. 3.
Fig. 3.
Common components in the application of the SEURAT-1 risk assessment workflow to two case study safety assessments for systemic effects.
See this image and copyright information in PMC

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