Read-across lets data from one chemical be used for structurally and biologically similar chemicals to meet REACH information requirements, reducing the need for new animal studies. This study tested whether the three xylene isomers (ortho-, meta- and para-xylene) and ethylbenzene are metabolised similarly enough to support read-across between them. It also tested whether exposure to a mixture changes how each one is metabolised.
Each substance was incubated with rat liver S9 fractions, and its consumption was measured using a validated GC-MS method to determine Michaelis-Menten kinetics (Km and Vmax). The results were used to predict how each component would be metabolised in a mixture representing the REACH-registered reaction mass of ethylbenzene and xylene (EC 905-588-0). That mixture was then tested experimentally.
All four substances showed similar metabolic kinetics, and the measured consumption rates for the mixture matched the predicted values, indicating no enzyme inhibition. Metabolism rates did not differ whether the substances were tested alone or together. Given their metabolic and structural similarities, data from the xylene isomers can be read across to each other and to xylene reaction mass substances. This supports the 3Rs and REACH’s principle of using animal testing only as a last resort.
Authors
C. Haines, L. G. Higgins, N. Aygun Kocabas, M. Rooseboom, F. Faulhammer, J. Sanchez, S. Schuchardt, K. Bluemlein
In Vitro Metabolism of Ethylbenzene and Xylene Isomers in Rat Liver S9. EUROTOX 2025, Poster P35-10 (Varia).