Context and Challenge
Chemical and manufacturing companies face growing regulatory pressures related to chemical product safety. The REACH regulation (EC No. 1907/2006) requires companies to identify and replace hazardous substances with safer alternatives, a process that demands specialized toxicological expertise and the analysis of vast databases of chemical structures and regulations.
The main challenge lies in quickly identifying structurally similar alternatives to a substance of interest, while simultaneously verifying their safety against current regulatory profiles—particularly for cosmetics, food contact materials (FCM), and industrial solvents.
Developed Solution: Suite ToxEraser
Within the research project “Life Vermeer – Integrating VEGA, ToxRead, MERLIN-Expo, and ERICA in a platform for risk assessment and substitution of risky substances” (LIFE16 ENV/IT/000167) coordinated by the Mario Negri Institute for Pharmacological Research IRCCS, Kode contributed to developing three standalone applications collectively named ToxEraser Tools, each dedicated to a specific application sector.
The tool, thanks to the integration of VEGA models and reference lists of compliant compounds meeting current regulatory requirements, is able to identify structural alerts (specific to each field of application) with high potential risk to human health in the molecule under study.
In addition, through similarity algorithms, ToxEraser is able to identify chemical analogies between molecules, to suggest possible candidates for the substitution of risky compounds.
Cosmetics Module
The cosmetics module compares the input substance’s structure with a database of 2,233 specifically regulated substances under Regulation (EC) No. 1223/2009. For each identified analogue, it provides:
- Regulatory classification (allowed, prohibited, restricted)
- Hazard alert based on QSAR models: Benigni/Bossa for genotoxicity, endocrine disruptor (ED) alerts, ToxTree analysis
- Chemical structure visualized with similarity score
Module FCM (Food Contact Materials)
The FCM module interfaces with the list of substances authorized by Regulation (EU) No. 10/2011 for plastic materials. Structural similarity search enables:
- Identify authorized analogues with their respective specific migration limit (SML)
- Flag any usage restrictions (e.g., only for contact with non-fatty foods)
- Support the assessment of NIAS (Non-Intentionally Added Substances)
Solvents Module
The solvents module supports the substitution of hazardous industrial solvents, with reference to ICH Q3C toxicological profiles and ECHA guidelines on sustainable solvents.
Application Example: DEP Analysis
Use Case: Substitution of Diethyl Phthalate (DEP)
Input substance: Diethyl phthalate (CAS 84-66-2) – plasticizer phthalate under regulatory scrutiny.
ToxEraser Results:
Structural alert confirmed: phthalate with potential endocrine disruption effect (Benigni/Bossa positive)
Suggested analogue: Phenylalanine (structural similarity 72%) – cosmetic classification: allowed, no ED alerts
PDF report generated in less than 3 seconds with comparative structure visualization
Impact and Benefits
ToxEraser Tools significantly reduces the time required for preliminary toxicological analysis during formulation. The company chemist can obtain a complete regulatory overview of available alternatives in just a few seconds, without the need to manually consult regulations and hazard databases. This accelerates the substitution process of substances of concern (SVHC), contributing to the objectives of the EU chemical sustainability strategy.