Read-across and new approach methodologies applied in a 10-step framework for cosmetics safety assessment - A case study with parabens

Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for the value added by new approach methodologies (NAMs) in read-across (RAX) for use in a next-generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics. In addition to structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data from PBK models, and bioactivity data are used to provide evidence of the chemical and biological similarity of PP and analogues and to establish potency trends for observed effects in vitro. The chemical category under consideration is short (C1-C4) linear chain n-alkyl parabens: methylparaben, ethylparaben, propylparaben and butylparaben. The goal of this case study is to illustrate how a practical framework for RAX can be used to fill a hypothetical data gap for reproductive toxicity of the target chemical PP.

Automated summary

This article provides a practical demonstration of a 10-step read-across (RAX) framework using propylparaben (PP) as a case study. It aims to establish the value of new approach methodologies (NAMs) in RAX for next-generation risk assessment (NGRA) in assessing the safety of consumer exposure to PP-containing cosmetics. Various data, including structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data, and bioactivity data, are used to establish the chemical and biological similarity of PP and analogues, as well as to identify trends in potency for observed effects in vitro. The case study focuses on short-chain (C1-C4) linear alkyl parabens: methylparaben, ethylparaben, propylparaben, and butylparaben. The goal of this study is to demonstrate how a practical RAX framework can be used to address hypothetical data gaps in reproductive toxicity for the target chemical PP.