[2] o-Toluidine is produced industrially by nitration of toluene to give a mixture of nitrotoluenes, favoring the ortho isomer.
The Report on Carcinogens (RoC) is a U.S. congressionally-mandated, science-based public health report that identifies agents, substances, mixtures, or exposures in the environment that pose a hazard to people residing in the United States[17] Since then, other cancer related studies have been published and the listing of o-toluidine was changed to 'known to be a human carcinogen'.
[19][13][20][21] The metabolism of o-toluidine involves many competing activating and deactivating pathways, including N-acetylation, N-oxidation, and N-hydroxylation, and ring oxidation.
Exposure to o-toluidine enhances the microsomal activity of aryl hydrocarbon hydroxylase (particularly in the kidney), NADPH-cytochrome c reductase and the content of cytochrome P-450.
N-Hydroxy-o-toluidine can be either metabolized to o-nitrosotoluene or conjugated with glucuronic acid or sulfate and transported to the urinary bladder via the blood.
Once in the bladder, N-hydroxy-o-toluidine can be released from the conjugates in an acidic urine environment to either react directly with DNA or be bio-activated via sulfation or acetylation by cytosolic sulfotransferases or N-acetyltransferases (presumably NAT1).
These metabolites can produce reactive oxygen species, resulting in oxidative cellular damage and compensatory cell proliferation.