I've recently been using the RDKit One Component Reaction node with one Reaction Transformation (inputted as a RXN type in the 2nd port), and having 250,000 substrates.
The transformation was quite simple, it was simply alkylating an aryl-NH2 with a specified alkyl group in the reaction transformation.
However, the node seemed quite tempermental in operating, I consistently kept getting errors part way through the node completion saying "RDKit General Exception". After multiple attempts, a reboot of the machine, and then finally putting in the node to "Write tables to Disk", it worked on the second attempt.
There may be some memory leaks or issues somewhere, as the reaction transformation and substrates stayed constant, yet sometimes it gave this error, and then eventually it worked.