Thresholds of Toxicological Concern for cosmetics-related substances: New database, thresholds, and enrichment of chemical space

Abstract

a b s t r a c tA new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-AdverseEffect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 mg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 mg/kg-bw/day are broadly similar to those of the original Munro dataset.

A Next-Generation Risk Assessment Case Study for Coumarin in Cosmetic Products

“…However, it may not always be necessary or possible to identify a specific pathway or AOP for a chemical to carry out a risk assessment. In some cases, risk assessments can be completed using low tier approaches such as exposure-based waiving ( Yang et al , 2017 ), history of safe use ( Constable et al , 2007 ; Neely et al , 2011 ), read-across ( Ball et al , 2016 ), or in vitro OECD test methods that require minimal data generation (eg, genotoxicity, skin, and eye irritation) ( OECD, 2017 , 2018a , b , 2019a , b ).…”

Unlocking the potential of in silico chemical safety assessment – A report on a cross-sector symposium on current opportunities and future challenges

“…while the cosmetics industry is primarily concerned with the dermal and inhalation routes, oral absorption is more important for the pharmaceutical and food industries. The TTC approach is seen as a simple and practical means of safety assessment based on information on chemical structure and exposure alone [31] ; it may also assist in the evaluation of mixtures of synthetic and natural products. There is an increasing need to consider internal exposures to chemicals, again through the modelling of the distribution of chemicals.…”

Ab initio chemical safety assessment: A workflow based on exposure considerations and non-animal methods

“…However, as in the case of cosmetics, the primary route of exposure might be dermal. Within the COSMOS project the TTC non-cancer dataset was enhanced with several hundred substances related to cosmetic ingredients [40] , [99] and the applicability of the TTC approach was evaluated both for oral exposure [98] , [99] and for dermal exposure, taking into account bioavailability differences between dermal and oral exposure [97] .…”

“…The aim was to develop a structured risk assessment workflow for repeated dose toxicity, with the goal of predicting a no-adverse effect level of a cosmetic relevant ingredient, assuming a certain exposure scenario. Within the context of this workflow, the Threshold of Toxicological Concern (TTC) approach, evaluated by the COSMOS project ( http://www.cosmostox.eu/ ; [98] , [99] ) and refined for dermal exposure [97] , was applied to support a low exposure scenario. In addition, read-across was incorporated to strengthen the non-animal evidence with structurally similar substances and make biological links to higher order outcomes [3] , [8] .…”