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Converging Degradation Pathways as a Basis for Grouping & Read-Across

By March 18, 2024No Comments

We are pleased to share the poster our colleague Arno Wess presented at SETAC in 2023.

Title: “Converging Degradation Pathways as a Basis for Grouping & Read-Across

Since the REACH legislation, Read-Across became a frequently used option for predicting toxicity and properties of chemicals. While (Quantitative)-Structure-Property-Relationships ((Q)SPR) have achieved some regulatory acceptance (e.g., for concluding of explosive properties or estimating vapour pressure of substances with a melting point above 200 °C), the derivation of biological effects is often not very solid and gets refused. Formaldehyde Releasers are a good example for a straight-forward applicable Read-Across. The cleaving of Formaldehyde(CAS 50-00-0) is often the intended property of chemicals. It represents an important and rather fast primary degradation step. The remainder of the parent molecule normally does not degrade fast and shows little bioactivity, while Formaldehyde is readily biodegradable (ECHA registered dossier 15858). Therefore, short-term effects after (in relation to the formed Formaldehyde) isomolar exposure are likely to be comparable. In contrast, long-term effects to low doses can be expected to be influenced by the other degradation products. Any grouping must be precisely defined and justified in agreement with the guidance documents of the authorities. The applicability domain may comprise only few or just one well defined endpoint. This is particularly necessary if the grouping is based on metabolism/transformation, but the group members differ in terms of degradation times and the number of required transformation steps. Nonetheless, more complex grouping could be based on converging pathways (leading with at least one branch to an identical toxicophoric chemical), where the relevant metabolite or transformation product is formed after some antecedent degradation steps.