Increasing legislative requirements for registration and safety assessment of chemicals have demonstrated the need to obtain toxicological information without resorting to animal testing. Eliminating animal testing for human health endpoints is a significant challenge in consumer safety risk assessment. Read across is a powerful tool for filling data gaps and predicting the toxicity of untested chemicals. It provides a transparent and systematic approach to regulatory acceptance and a strategy to evaluate similarity based chemical clustering. Read across framework relies on structure activity relation (SAR) between the target chemical and the read across analog. SAR is extended to predict toxicokinetic and toxicodynamic properties. A more useful tool for demonstrating commonality in toxicity is through adverse outcome pathway concept which implies assessing similarity via molecular initiating events, key intermediate events and other relevant in-vitro information and data. To build read across, we adopt toxicological Mode of Action (MoA) framework that can describe a mechanistic explanation of the observed effect. We use this technic to study the toxic effect of fragrance materials on systemic as well as local human health endpoints and on the environment. We assess similarity and uncertainty. Scientific justification is given to explain clustering, bioavailability, metabolism and mechanistic plausibility. To identify read across analog, our strategy for structuring and reporting a read-across prediction of toxicity described is consistent with the guidance provided by OECD on the reporting of defined approached used within Integrated Approaches for Testing and Assessment or IATA and the European Chemical Agency (ECHA) read-across assessment framework or RAAF.

Read-across approach for predicting the toxicity of fragrance materials

254th National Meeting (2017)

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