COSMOS next generation - A public knowledge base leveraging chemical and biological data to support the regulatory assessment of chemicals

C Yang; M T D Cronin; K B Arvidson; B Bienfait; S J Enoch; B Heldreth; B Hobocienski; K Muldoon-Jacobs; Y Lan; J C Madden; T Magdziarz; J Marusczyk; A Mostrag; M Nelms; D Neagu; K Przybylak; J F Rathman; J Park; A-N Richarz; A M Richard; J V Ribeiro; O Sacher; C Schwab; V Vitcheva; P Volarath; A P Worth

doi:10.1016/j.comtox.2021.100175

COSMOS next generation - A public knowledge base leveraging chemical and biological data to support the regulatory assessment of chemicals

Comput Toxicol. 2021 Aug:19:100175. doi: 10.1016/j.comtox.2021.100175.

Authors

C Yang^{1

2}, M T D Cronin³, K B Arvidson⁴, B Bienfait², S J Enoch³, B Heldreth⁵, B Hobocienski¹, K Muldoon-Jacobs⁴, Y Lan⁶, J C Madden³, T Magdziarz², J Marusczyk², A Mostrag¹, M Nelms³, D Neagu⁶, K Przybylak³, J F Rathman^{1

7}, J Park¹, A-N Richarz³, A M Richard⁸, J V Ribeiro¹, O Sacher², C Schwab², V Vitcheva^{1

2}, P Volarath⁴, A P Worth⁹

Affiliations

¹ MN-AM, Columbus, OH, USA.
² MN-AM Nürnberg, Germany.
³ School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, UK.
⁴ US FDA CFSAN College Park, MD, USA.
⁵ Cosmetic Ingredient Review, Washington, DC, USA.
⁶ University of Bradford, UK.
⁷ The Ohio State University, Columbus OH, USA.
⁸ US EPA RTP, NC, USA.
⁹ European Commission, Joint Research Centre (JRC), Ispra, Italy.

Abstract

The COSMOS Database (DB) was originally established to provide reliable data for cosmetics-related chemicals within the COSMOS Project funded as part of the SEURAT-1 Research Initiative. The database has subsequently been maintained and developed further into COSMOS Next Generation (NG), a combination of database and in silico tools, essential components of a knowledge base. COSMOS DB provided a cosmetics inventory as well as other regulatory inventories, accompanied by assessment results and in vitro and in vivo toxicity data. In addition to data content curation, much effort was dedicated to data governance - data authorisation, characterisation of quality, documentation of meta information, and control of data use. Through this effort, COSMOS DB was able to merge and fuse data of various types from different sources. Building on the previous effort, the COSMOS Minimum Inclusion (MINIS) criteria for a toxicity database were further expanded to quantify the reliability of studies. COSMOS NG features multiple fingerprints for analysing structure similarity, and new tools to calculate molecular properties and screen chemicals with endpoint-related public profilers, such as DNA and protein binders, liver alerts and genotoxic alerts. The publicly available COSMOS NG enables users to compile information and execute analyses such as category formation and read-across. This paper provides a step-by-step guided workflow for a simple read-across case, starting from a target structure and culminating in an estimation of a NOAEL confidence interval. Given its strong technical foundation, inclusion of quality-reviewed data, and provision of tools designed to facilitate communication between users, COSMOS NG is a first step towards building a toxicological knowledge hub leveraging many public data systems for chemical safety evaluation. We continue to monitor the feedback from the user community at support@mn-am.com.

Keywords: AOP, Adverse Outcome Pathway; Analogue selection; CERES, Chemical Evaluation and Risk Estimation System; CFSAN, Center for Food Safety and Applied Nutrition; CMS-ID, COSMOS Identification Number; COSMOS DB, COSMOS Database; COSMOS MINIS, Minimum Inclusion Criteria of Studies in COSMOS DB; COSMOS NG, COSMOS Next Generation; CRADA, Cooperative Research and Development Agreement; CosIng, Cosmetic Ingredient Database; DART, Developmental & Reproductive Toxicity; DB, Database; DST, Dempster Shafer Theory; Database; ECHA, European Chemicals Agency; EFSA, European Food Safety Authority; Guided workflow; HESS, Hazard Evaluation Support System; HNEL, Highest No Effect Level; HTS, High throughput screening; ILSI, International Life Sciences Institute; IUCLID, International Uniform Chemical Information Database; Knowledge hub; LEL, Lowest Effect Level; LOAEL, Lowest Observed Adverse Effect Level; LogP, Logarithm of the octanol:water partition coefficient; NAM, New Approach Methodology; NGRA, Next Generation Risk-Assessment; NITE, National Institute of Technology and Evaluation (Japan); NOAEL, No Observed Adverse Effect Level; NTP, National Toxicology Program; OECD, Organisation for Economic Co-operation and Development; OpenFoodTox, EFSA’s OpenFoodTox database; PAFA, Priority-based Assessment of Food Additive database; PK/TK, Pharmacokinetics/Toxicokinetics; Public database; QA, Quality Assurance; QC, Quality Control; REACH, Registration, Evaluation, Authorisation and Restriction of Chemicals; SCC, Science Committee on Cosmetics (EU); SCCNFP, Scientific Committee of Cosmetic Products and Non-food Products intended for Consumers (EU); SCCP, Scientific Committee on Consumer Products (EU); SCCS, Scientific Committee on Consumer Safety (EU); Study reliability; TTC, Threshold of Toxicological Concern; ToxRefDB, Toxicity Reference Database; Toxicity; US EPA, United States Environmental Protection Agency; US FDA, United States Food and Drug Administration.