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I think a lot of (especially inexpensive) sensors do connect the SCL/SDA to incoming voltage without any isolation. I know the Atlas circuits all do and it seems like your ADC does as well. But I’ve seen other I2C devices that work fine with the Mayfly switched power going off – I think the Bosch BME280 and INA291’s I played with, but I’m not positive which others. I’m not sure if in those cases the breakouts I had were actually isolated or if it was just luck and resistor magic that the let the internal pull ups on the Mayfly’s I2C lines overpower the pull down when power went out. I suspect the latter.
In theory, the I2C isolation should work. But I haven’t ever actually bought an isolator myself to test.