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There are no in vivo studies on the absorption of o-anisidine. Oral, dermal and resorption after inhalational exposure can be assumed as systemic effects were observed in toxicological studies. In vitro test showed that metabolism seems to be comparable to other aromatic amines: it encompasses amine group acetylation and ring oxidation. Furthermore activation occurs via O-acetylation as well as peroxidation via enzymes like prostaglandin-H-synthase (note: o-anisidine is also a substrate of thyroid peroxidase, Thyroid peroxidase inhibition with concomitantly decreased thyroid hormone formation is known to induce thyroid tumors. This might be one reason for the increased thyroid tumor incidence observed in male rats in a two year feeding study.). Furthermore, O-demethylation may appear as can be concluded from in vitro studies with microsomes from rat liver.

In urine, the follwing metabolites were found:

N-acetyl-2-methoxyaniline and N-acetyl-4-hydroxy-2-methoxyaniline (in vivo findings). In vitro studies revealed further metabolites e.g. N-(2 -methoxyphenyl)hydroxylamine and o-aminophenol (as well as one structurally unknoown compound).

Subsequently N-(2-Methooxyphenyl)hydroxylamine can be either oxidized to o-nitroanisole or reduced to parental o-anisidin which then can be proceeded to o-aminophenol. The submission substance appears to be a good substrate of a variety of microsomal P450 enzymes (see test with purified cytochromes). P450 2E1 of rabbits seems to be the most efficient enzyme catalyzing the conversion of o-anisidine.

In vivo the highest levels of substance was found in liver, kidneys and in the muscle tissue after 12 h post injection. Over time only a moderate decline in ³H levels was seen in most tissues. Nevertheless, the authors of this study state that this "prolonged ³H retention observed" in most of the examined tissues indicate that "o-anisidine, especially in case of repeated exposure, might accumulate in the body." This is in contrast to the RAR where the authors concluded that due to the log Pow and the rapid excretion o-anisidine is unlikely to bioaccumulate in the organism, this new data indicate that there is a potential for bioaccumulation inherited in o-anisidine.

In several in vivo studies the main excretion route is proved to be urine, about 70 to >90% within 72 to 96 h.The majority was excreted within the first 24 h.