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Description of key information

o-Toluidine is rapidly absorbed via gastrointestinal tract and is rapidly distributed, metabolized and excreted mainly via urine. although there are no special toxicokinetik data on absorption via skin and respiratary tract , absorptions via this administration routes is shown by data from acute toxicity.

Key value for chemical safety assessment

Additional information

OECD/SIDS of o-toluidine published by UNEP in 2006 summarizes:

Studies in Animals:

There are no special toxicokinetic data on absorption via skin and respiratory tract but respective acute toxicity studies indicate absorption via these administration routes.

Following oral application of 500 mg toluidine/kg bw to rats a half-life time of plasma elimination of 12 to 15 hours was derived (Brock, Hundley and Lieder, 1990); i.v. application of app. 111 mg/kg bw to dogs yielded a half-life time of plasma elimination of half an hour (Kiese, 1963). 48 hours following subcutaneous injection of labelled o-toluidine hydrochloride into rats, Son, Everett and Fiala (1980) detected radioactivity in decreasing range: liver > kidney > spleen, colon > lung and bladder. In another study 72 hours following oral application to rats, radioactivity was detected in decreasing range: whole blood > spleen > kidney > liver > subcutaneous abdominal fat > lung > heart > abdominal skin> bladder >gastrointestinal tract > bone marrow > brain > muscle > testes (Brock, Hundley and Lieder, 1990). The results from metabolism study in rats show that N-acetylation and hydroxylation at the position 4 of the aromatic ring of o-toluidine are the major metabolic pathways in rats. Minor pathways include hydroxylation at position 6, oxidation of the methyl-group and oxidation of the amino-group. Sulphate conjugates predominate over glucuronides by a ratio of 6:1. The metabolites which were found included azoxytoluene, onitrosotoluene, N-acetyl-o-toluidine, N-acetyl-o-aminobenzyl alcohol, 4-amino-m-cresol, N-acetyl- 4-amino-m-cresol, anthranilic acid, N-acetyl-anthranilic acid, 2-amino-m-cresol, other unidentified substances and unchanged o-toluidine (Son, Everett and Fiala, 1980).

In rats, unchanged o-toluidine and the metabolites are largely excreted in the urine: 48 hours after s.c. injection up to 83 % of the dose (Son, Everett and Fiala, 1980) and 72 hours after oral application up to 94.7 % of the dose (Cheever, Richards and Plotnick, 1980). Faecal excretion and exhalation of the substance is minimal with up to 3.5 % and 1.46 % of the dose (Son, Everett and Fiala, 1980).

Studies in humans

Biological Monitoring to assess human exposure to o-oluidine indicates that absorption may occur though inhalation and dermal contact; however, quantitative information was not identified. o-toluidine binds to hemoglobin. N-acetylated metabolites of o-toluidine are eliminated in the urine (CICAD 1988)

Overall conclusion

o-Toluidine is rapidly absorbed via gastrointestinal tract and is rapidly distributed, metabolized and excreted mainly via urine. Although there are no special toxicokinetic data on absorption via skin and respiratory tract, absorption via these administration routes is shown by data from acute toxicity studies