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Conference Papers Year : 2016

Integration of alternative methods for an ab initio chemical safety assessment

Alicia Paini
  • Function : Author
Elisabet Berggren
  • Function : Author
Catherine Mahony
  • Function : Author
Gladys Ouedraogo
  • Function : Author
Andrea-Nicole Richarz
  • Function : Author
Andew White
  • Function : Author


Assessing chemical safety using only non-animal methods is a major challenge within the European Union, especially considering the ban to market cosmetics with ingredients tested on animals (Regulation 1223/2009). One of the outcomes of the SEURAT-1 initiative (, co-sponsored by the European Commission 7thFP and Cosmetics Europe, was to develop case studies addressing that issue. Besides a read-across case-study, where "new approach" data was used to strengthen the confidence in reading across data from an already assessed chemical to a structural analogue, an ab initio case study was carried out and is presented here. The ab initio case study was an attempt to structure knowledge and data in a logic workflow which could be used for decision making to predict whether the intended exposure could be considered safe based on data solely from alternative methods. The workflow is includes the following steps: i) identification of the exposure/use scenario; ii) data collection on the chemical; iii) toxicokinetic and toxicodynamic modeling; iv) evaluation of other alternative methods (in vitro or in silico) which are available and could provide evidence for a hypothesis on the chemicals' mode of action; v) confirmation of the hypothesis with targeted testing using selected in vitro or in silico methods; vi) propose a risk valuation, as well as estimating uncertainties and identifying data gaps. The exposure scenario is an initial and essential step in this workflow. Whether exposure is intentional or not it should be considered, and in both cases estimates of the doses, expected routes of exposure, frequency and length of exposure should be made. The ab initio workflow was applied to the piperonyl butoxide (PBO), as a hypothetical case, for which the mode-of-action was assumed to be unknown. The only data on the compound was the molecular structure and a concentration of PBO in a consumer product formulation. An exposure scenario was set up and data were generated for simulation of internal exposure for a “healthy human” using PBPK modeling. The concentration in blood and liver predicted by the model were then used to design in vitro tests (performed by SEURAT-1 partners). The test results were then evaluated and used to estimate whether PBO would be safe to use for the selected exposure scenario. To our knowledge, the SEURAT-1 ab initio case study is a first attempt to shift our minds to a fully non-animal based chemical risk assessment relying only on alternative methods.


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Dates and versions

ineris-01854697 , version 1 (07-08-2018)


  • HAL Id : ineris-01854697 , version 1


Alicia Paini, Elisabet Berggren, Frédéric Y. Bois, Catherine Mahony, Gladys Ouedraogo, et al.. Integration of alternative methods for an ab initio chemical safety assessment. ISES 2016 Annual Meeting, Oct 2016, Utrecht, Netherlands. pp.777. ⟨ineris-01854697⟩


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